Vascular System PDF

Circulatory System Red Blood Cells The only known hemoglobinopathy of animals is porphyria. Although described in several species, it is most important as a cause of photosensitivity in cattle (see Photosensitization: Introduction). In most species, the kidney is both the sens...

Circulatory System Red Blood Cells The only known hemoglobinopathy of animals is porphyria. Although described in several species, it is most important as a cause of photosensitivity in cattle (see Photosensitization: Introduction). In most species, the kidney is both the sensor organ and the major site of erythropoietin production, so chronic renal failure is associated with anemia. Erythropoietin acts on the marrow in concert with other humoral mediators to increase the number of stem cells entering RBC production, to shorten maturation time, and to cause early release of reticulocytes. Removal of aged RBC normally occurs by phagocytosis by the fixed macrophages of the spleen. After phagocytosis and subsequent disruption of the cell membrane, Hgb is converted to heme and globin. Iron is released from the heme moiety and either stored in the macrophage as ferritin or hemosiderin, or released into the circulation for transport back to the marrow. The remaining heme is converted to bilirubin, which is released by the macrophages into the systemic circulation where it complexes with albumin for transport to the hepatocytes; there, it is conjugated and excreted into the bile. In extravascular hemolytic anemias, RBC have a shortened life span, and the same mechanisms occur at an increased rate. About 1% of normal aging RBC are hemolyzed in the circulation, and free Hgb is released. This is quickly converted to Hgb dimers that bind to haptoglobin and are transported to the liver, where they are metabolized in the same manner as are products from RBC removed by phagocytosis. In intravascular hemolytic anemia, more RBC are destroyed in the circulation (hemoglobinemia) than can be bound to haptoglobin. The excess Hgb and, therefore, iron are excreted in the urine (hemoglobinuria). The principal metabolic pathway of RBC is glycolysis, and the main energy source in most species is glucose. The energy of ATP is used to maintain RBC membrane pumps so as to preserve shape and flexibility. The glucose not used in glycolysis is metabolized via a second pathway, the hexose monophosphate (HMP) shunt. No energy is produced via the HMP shunt; its principal effect is to maintain reducing potential in the form of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Excessive oxidant stress may overload the protective HMP shunt or methemoglobin reductase pathways and, thereby, cause Heinz body hemolysis or methemoglobin formation, respectively. Hemolytic anemias caused by certain drugs, such as phenothiazine in horses or acetaminophen in cats, are examples of this mechanism. See also anemia, Anemia of Chronic Disease , Chicken Anemia Virus Infection: Introduction , Equine Infectious Anemia: Introduction , Hemobartonellosis , Autoimmune Hemolytic Anemia and Thrombocytopenia. Iron is the limiting factor in chronic blood loss. Hemolysis may be caused by toxins, infectious agents, congenital abnormalities, or antibodies directed against RBC membrane antigens. Decreased RBC production may result from primary marrow diseases (such as aplastic anemia, hematopoietic malignancy, or myelofibrosis) or from other causes such as renal failure, drugs, toxins, or antibodies directed against RBC precursors. White Blood Cells Phagocytes: Mononuclear phagocytes arise primarily from the marrow and are released into the blood as monocytes. They may circulate for hours to a few days before entering the tissues and differentiating to become macrophages. Granulocytes have a segmented nucleus and are classified according to their staining characteristics as neutrophils, eosinophils, or basophils.. Neutrophils circulate for only a few hours before travelling to the tissues. Lymphocytes: Lymphocytes are responsible for both humoral and cellular immunity. Lymphocyte production in mammals originates in the bone marrow. Some of the lymphocytes destined to be involved in cellular immunity migrate to the thymus and differentiate further under the influence of thymic hormones. These become “T cells” and are responsible for a variety of helper, suppressor, or cytotoxic immunologic functions. Most circulating lymphocytes are T cells, but many are also present in the spleen and lymph nodes. The B cells migrate directly to organs without undergoing modification in the thymus and are responsible for humoral immunity (antibody production). Thus, lymphoid organs have populations of both B and T lymphocytes. In the lymph nodes, follicular centers are primarily B cells, and parafollicular zones are primarily T cells. In the spleen, most of the lymphocytes of the red pulp are B cells, whereas those of the periarteriolar lymphoid sheaths are T cells. The humoral immune system is composed of B lymphocytes that produce antibodies of several classes. When sensitized B lymphocytes encounter antigen, they undergo blast transformation, divide, and differentiate into plasma cells that produce antibody. Therefore, each B lymphocyte initially stimulated produces a clone of plasma cells, all producing the same specific antibody. Merck Veterinary Manual - Summary 2  Antibody molecules (immunoglobulins) fall into several classes, each with its own functional characteristics. For example, IgA is the principal antibody of respiratory and intestinal secretions, IgM is the first antibody produced in response to a newly recognized antigen, IgG is the principal antibody of the circulating blood, and IgE is the principal antibody involved in allergic reactions. Helper T cells are required for full expression of a humoral immune response. Suppressor T cells dampen the production of a given antibody. Natural killer cells, which are a class of lymphocyte distinct from T cells and B cells, destroy foreign cells (eg, neoplastic cells) even without prior sensitization. Lymphocyte response in disease may be appropriate (activation of the immune system) or inappropriate (immune- mediated disease and lymphoproliferative malignancies). See also immune system et seq. Immune-mediated disease results from failure of the immune system to recognize host tissues as self. For example, in immune-mediated hemolytic anemia, antibodies are produced against the host's own RBC. Platelets Platelets form the initial hemostatic plug whenever hemorrhage occurs. They also are the source of phospholipid, which is needed for coagulation factors to interact to form a fibrin clot. Platelets are produced in the bone marrow from megakaryocytes, under the influence of thrombopoietin. Platelet production begins with invagination of the megakaryocyte cell membrane and the formation of cytoplasmic channels and islands. Platelet disorders are either quantitative (thrombocytopenia or thrombocytosis) or qualitative (thrombocytopathy). Thrombocytopenia is one of the most common bleeding disorders of animals. In general, platelet counts must fall to 75% of canine lymphomas are of B-cell origin, and 10-20% are of T-cell origin. B-cell neoplasms are associated with better response and longer remission and survival times than T-cell neoplasms. There is a strong correlation between some T-cell neoplasms and hypercalcemia (especially with T-cell lymphomas involving the thymus and bone marrow), and these tumors are associated with poorer response rates and shorter survival and remission times. Treatment: Most treatment regimens use a combination of cyclophosphamide, vincristine, and prednisone. The addition of asparaginase or adriamycin has improved response rates and survival times. Adverse reactions include bone marrow suppression, increased susceptibility to infection, and hemorrhagic cystitis from cyclophosphamide. Use of antibiotics in an attempt to prevent these occurrences is controversial. Chemotherapy is generally divided into an induction phase, in which a combination of drugs is administered intensively over a short period of time, and a maintenance phase. Maintenance: The diffuse alimentary form of lymphosarcoma often responds poorly to chemotherapy. However, if the lesion is localized to a segment of the intestine, surgical resection followed by chemotherapy should be performed. In this case, the prognosis is guarded to fair for long-term response. Treatment of lymphoblastic leukemia has been less successful, with a median survival time of 200 times/min in the cat, and 60-160 times/min in the dog. In general, the larger the species, the slower the rate of SA node discharge and the slower the heart rate. The rate of SA node discharge increases, often to nearly 300 beats/min, when norepinephrine is released from the sympathetic nerves and binds to the β1-adrenoreceptors on the SA node. This cardioacceleration may be blocked by β- adrenergic blocking agents (eg, propranolol, atenolol, metoprolol). The rate of SA node discharge decreases when acetylcholine released by the parasympathetic (vagus) nerves binds to the cholinergic receptors on the SA node. This vagally mediated cardiodeceleration may be blocked by a parasympatholytic (vagolytic) compound (eg, atropine, glycopyrrolate). In quiet, healthy dogs, the heart rate is usually irregular. It increases during inspiration and decreases during expiration. This is termed respiratory sinus arrhythmia and results from decreased vagal activity during inspiration and increased vagal activity during expiration. Therefore, vagolytic compounds, as well as excitement, pain, or fever, usually abolish or diminish respiratory sinus arrhythmia. Heart rate is also inversely related to systemic arterial blood pressure. When blood pressure increases, heart rate decreases; when blood pressure decreases, heart rate increases. This relationship is known as the Marey reflex and occurs by the following mechanisms. When high-pressure arterial baroreceptors in the aortic and carotid sinuses detect the fall in blood pressure, they send increased afferent volleys to the medulla oblongata, which decreases vagal efferents to the SA node and causes the heart rate to increase. When blood pressure increases, heart rate slows due to increased vagal efferents to the SA node. In heart failure, the baroreceptors “believe” that blood pressure is too low, even though this may not be so. Thus, the baroreceptors initiate compensatory mechanisms (eg, arterial and arteriolar constriction, venous constriction, increase in heart rate) designed to increase blood pressure that, unfortunately, injure the heart. Whatever speeds or slows the rate of discharge of the SA node also speeds or slows conduction through the AV node. Thus, when heart rate is fast, the PQ is short; when heart rate is slow, the PQ is long. Force of Ventricular Contraction: The force with which the ventricles contract is determined by three factors: 1) the end-diastolic volume or preload, which is the volume of blood within the ventricles just before they begin to contract, 2) myocardial contractility or the inotropic state, which is the rate of cycling of the microscopic contractile units of the myocardium, and 3) the afterload, which is the interference to ejection of blood from the ventricle into and through the arterial tree. The afterload is measured as the peak tension the myocardium must generate to eject blood. The preload is the difference in end-diastolic pressure between the ventricle and the pleural space, divided by the stiffness of the ventricular myocardium. The preload is regulated predominantly by low-pressure volume receptors in the heart and large veins. When these receptors are stimulated by an increase in blood volume or by distention of the structures the receptors occupy, the body responds by making more urine and by dilating the veins—an attempt to decrease blood volume and lower the pressures in the veins responsible for venous distention. Myocardial contractility is determined by the rate of liberation of energy from ATP, which is determined, in part, by the amount of norepinephrine binding to β-1 adrenergic receptors in the myocardium. The afterload is determined by the relative stiffness of the arteries and by the degree of constriction or dilatation of the arterioles, both of which are determined by the degree of constriction or relaxation of the arterial and arteriolar vascular smooth muscle. The tone of vascular smooth muscle depends on many factors, some of which constrict the muscle (eg, α-1, angiotensin II, vasopressin, endothelin) and some of which relax the muscle (eg, β-2, atriopeptin, bradykinin, adenosine, nitric oxide). Afterload and peak tension are also determined by the preload and thickness of the ventricular wall just before ejecting. In fact, peak tension is equal to the preload times the diastolic arterial blood pressure, all divided by the end-diastolic wall thickness of the ventricle. Oxygen and the Myocardium: The amount of oxygen delivered to the heart depends on how well the lung functions, how much hemoglobin (Hgb) is present to carry the oxygen, and how much blood carrying the Hgb flows through the heart muscle via the coronary arteries. The amount of oxygen consumed by the heart is termed myocardial oxygen consumption. It is determined, principally, by heart rate, myocardial contractility, and afterload. Myocardial oxygen consumption is higher when each of the determinants is higher, and lower when each of the determinants is lower. Both heart rate and myocardial contractility are Merck Veterinary Manual - Summary 10 increased by β-l adrenergic stimulation (or by norepinephrine) and are decreased by an increase in parasympathetic stimulation; therefore, autonomic activity also influences myocardial oxygen consumption. In heart failure, inappropriate handling of calcium may be the most important factor that leads to both reduced force of contraction and reduced rate of relaxation (ie, reduced systolic as well as diastolic function). Interference to the Flow of Blood: Most (80%) of the interference to blood flow is from the degree of constriction or dilatation of the arterioles, termed the vascular resistance; however, some interference is from the stiffness of the portion of the great arteries closest to the ventricles, termed the impedance. One of the most important features of heart failure that leads to morbidity is increased resistance of arterial, arteriolar, and venous smooth muscle. This results because of increased angiotensin II and vasopressin due to (incorrect) compensatory feedback from the high-pressure baroreceptors to the medulla that blood pressure is too low. If the left ventricle is unable to eject a normal stroke volume or cardiac output, it is reasonable that the ventricular function might be improved by decreasing both vascular resistance and impedance—which is precisely why drugs that relax vascular smooth muscle are useful. Principles Of Therapy: Overview The following are general goals of therapy for heart disease. 1) Chronic stretch on myocardial fibers should be minimized because chronic stretch injures and irritates fibers, causes them to consume excess quantities of oxygen, and leads to their death and replacement by fibrous connective tissue (remodeling). 2) Edema fluid should be removed because it makes the lung wet, heavy, and stiff, and causes ventilation-perfusion inequalities and fatigues muscles of ventilation. 3) The circulation should be improved and the amount of regurgitation (most often mitral regurgitation) decreased. Improved circulation enhances blood flow to important organs, and reducing mitral regurgitation decreases stretch on the left atrium and pulmonary veins, decreases pulmonary capillary pressure, and decreases edema formation. 4) Heart rate and rhythm should be regulated. A heart beating too slowly fails to eject enough blood. A heart beating too rapidly does not have time and consumes too much oxygen at a time when there is too little coronary blood flow. A heart beating too irregularly may deteriorate into ventricular fibrillation and sudden death. 5) Oxygenation of the blood should be improved. Inadequate oxygenation leads to inadequate energy to fuel both contraction and relaxation of the myocardium. Inadequate oxygenation of the myocardium may also lead to arrhythmia. 6) β1-adrenergic receptors should be “up regulated.” “Down regulation” of β1-adrenergic receptors interferes with the ability to fight diseases of other organ systems. 7) The likelihood of thromboembolism should be minimized. Cats with hypertrophic cardiomyopathy may shed emboli from the enlarged left atrium, which may plug up major arterial branches and lead to ischemia and death. 8) Mature heartworms and microfilariae should be killed. Mature heartworms may initiate severe changes in the pulmonary arteries that ultimately impede blood flow through the lung. The ultimate goals of therapy for cardiovascular disease are achieved when the animal can be classified as functional Class I, the respiratory and heart rates are not increased at rest, and there is a respiratory sinus arrhythmia. Common Therapeutic Agents Furosemide is a diuretic that decreases resorption of provisional urine at the loop of Henle. It is also a venodilator when used IV. Theophylline is a bronchodilator and strengthens the muscles of ventilation. Chlorothiazide is a diuretic that decreases resorption of provisional urine at the distal convoluted tubule. It is used when furosemide diuresis either stops or is inadequate. (Note: All thiazides possess similar actions.) Spironolactone is a potassium-sparing diuretic that blocks aldosterone; it exerts its diuretic effect at the distal convoluted tubule. Amiloride and triamterine have similar modes of action. Digitalis glycosides exert their effects by inhibiting membrane Na-K-ATPase. Digoxin increases the force of myocardial contraction, slows the heart rate, and improves baroreceptor function. It also strengthens muscles of ventilation. Enalapril is an angiotensin-converting enzyme inhibitor that blocks the conversion of angiotensin I to angiotensin II. It reduces afterload, thereby improving cardiac output and reducing mitral regurgitation. It also improves baroreceptor function and is a venodilator. Procainamide is an antiarrhythmic compound used to suppress ventricular arrhythmias. It is used most often for ventricular arrhythmias that are not life-threatening; it is given most often orally. Quinidine is similar to procainamide but is the drug of choice for treating atrial fibrillation in horses. Lidocaine is used only IV for emergency ventricular arrhythmias. Mexilitine is an oral compound similar to lidocaine. Atenolol, propranolol, and metoprolol are β-andrenergic blockers that slow the heart rate, suppress arrhythmias, and “up regulate” adrenergic receptors. Diltiazem is a calcium-channel blocker that is useful for slow ventricular rate in animals with atrial fibrillation. It is also used to decrease myocardial Merck Veterinary Manual - Summary 11 stiffness in cats with hypertrophic cardiomyopathy. Verapamil is also a calcium-channel blocker, but it reduces myocardial contractility more than diltiazem. Sotolol and amiodorone are antiarrhythmic compounds useful for managing all forms of arrhythmias, but there is relatively little clinical experience with them. Atropine and glycopyrrolate block the effects of the vagus nerve on the SA node. Because the vagus nerve slows discharge of the SA node and heart rate, these compounds speed heart rate and may be useful when the heart beats too slowly. Nitroglycerine is a venodilator that is usually applied in a paste form to the skin inside of the earflap or thigh. By dilating peripheral veins, blood pools in those veins, and left ventricular preload and pulmonary edema are decreased. Aspirin and coumadin are anticoagulants that may prevent thromboembolism in cats with cardiomyopathy. Taurine and l-carnitine are amino acids useful in preventing dilated cardiomyopathy in cats (taurine) and, in a limited number of dogs (l-carnitine). Thiacetarsamide is used to kill mature heartworms. Ivermectin and milbemycin are used to kill microfilariae. Anomalies Of Derivatives Of The Aortic Arches: Overview Patent Ductus Arteriosus In fetal life, oxygenated blood within the main pulmonary artery is shunted into the descending aorta through the ductus arteriosus, thereby bypassing the nonfunctional lungs. At birth, several factors mediate closure of the ductus, which effects separation of the systemic and pulmonary circulatory systems. Inflation of the lungs allows the pulmonary circulation to function as a low pressure system, and closure of the ductus prevents shunting of blood from the high pressure systemic circulatory system into the pulmonary artery. Pathophysiology: Persistence or patency of the ductus with an otherwise normal systemic and pulmonary circulatory system results in significant shunting of blood from left to right, ie, systemic to pulmonary. Because the pressure within the aorta is always higher than that of the pulmonary artery, shunting is continuous and produces the classic continuous, machinery-like murmur. The result is a volume overload of the pulmonary arteries and veins, left atrium, and left ventricle. Dilatation of these structures becomes evident. Left atrial and left ventricular dilatation may result in cardiac arrhythmias. Chronic volume overloading and dilatation of the left-sided cardiac chambers usually result in signs of left-sided congestive heart failure (pulmonary edema, cough, fatigue). Therefore, most untreated cases develop refractory congestive heart failure. Animals with a small ductus may reach adulthood without signs of heart failure but are at an increased risk of endocarditis. In a few untreated cases, increased pulmonary blood flow induces pulmonary vasoconstriction and development of pulmonary hypertension, which has several important implications. Shunting through the ductus slows and reverses, which causes disappearance of the murmur and occurrence of caudal cyanosis; the right ventricle becomes dilated and hypertrophied as a result of pulmonary vasoconstriction; and perfusion of the kidneys with desaturated blood causes excessive release of erythropoietin and subsequent polycythemia. Thus, if the ductus is shunting right to left, clinical signs of right ventricular failure (ascites, fatigue) and polycythemia (exercise intolerance, seizures) will predominate. In some cases, a right-to-left shunt is present at birth secondary to a patent ductus and retention of pulmonary vasculature (congenital pulmonary hypertension). Clinical Findings and Treatment: In animals with a PDA that shunts from left to right, a prominent, continuous, machinery-like murmur is present. The systolic component is loudest, heard best over the aortic valve area, and often associated with a precordial thrill. Most young animals do not demonstrate clinical signs. Those with a large shunt and older animals often have signs of left-sided congestive heart failure, eg, cough, tachypnea, exercise intolerance, and weight loss. Consistent electrocardiographic features include evidence of left ventricular and left atrial enlargement. Radiography demonstrates left atrial and left ventricular enlargement, prominent pulmonary vessels, aortic and pulmonic aneurysmal dilatations, and variable degrees of pulmonary edema. Echocardiography is not crucial in the diagnosis of PDA but is valuable in ruling out concurrent congenital cardiac defects. Surgical ligation of the ductus is curative and indicated in all cases deemed satisfactory anesthetic risks, considering the risk of congestive heart failure and endocarditis in untreated cases. If present, congestive heart failure should be medically managed (with diuretics, vasodilators, etc) before anesthesia and surgery. In animals with a PDA that shunts from right to left, there is usually a history of lethargy, exercise intolerance, and collapse. Careful examination may reveal differential cyanosis. Therapy involves control of polycythemia through periodic phlebotomies. Long-term prognosis is poor. Persistent Right Aortic Arch In this vascular ring anomaly, the right aortic arch persists, which causes obstruction of the esophagus at the level of the heart base. The esophagus is encircled by the persistent arch on the right, by the ligamentum arteriosum to the left and dorsally, and by the base of the heart ventrally. These congenital defects do not cause clinical signs referable to the cardiovascular system—signs of regurgitation and aspiration pneumonia predominate. Merck Veterinary Manual - Summary 12  Aortic Stenosis Left ventricular emptying may be obstructed at three locations: 1) subvalvular, consisting of a fibrous ridge of tissue within the left ventricular outflow tract; 2) valvular; and 3) supravalvular or obstruction distal to the aortic valve. The most common form in the dog is subaortic stenosis. Breed predilections have been identified for Boxers, Golden Retrievers, and Newfoundlands. Pathophysiology: Aortic stenosis induces left ventricular hypertrophy, the degree of which depends on the severity of the stenosis. In severe cases, left ventricular output may be decreased, especially during exercise. The major ramification of left ventricular hypertrophy is the creation of areas of myocardium with poor perfusion. Myocardial ischemia is a major factor in the development of serious life-threatening ventricular arrhythmias. Clinical Findings and Treatment: There may be a history of syncope and exercise intolerance. Animals with no history of illness may die suddenly, and the defect is first detected at necropsy. The degree of left ventricular hypertrophy and ejection velocity through the defect allow determination of severity and need for intervention. Treatment options include balloon valvuloplasty and surgical resection. The use of β-adrenergic blockers (propranolol, atenolol) have been advocated in animals experiencing syncope to reduce the frequency of arrhythmias. Affected animals should not be used for breeding. Pulmonic Stenosis Pulmonic stenosis is a common congenital cardiac defect in dogs. It results in obstruction to right ventricular emptying due, in most cases, to partial fusion and dysplasia of the pulmonic valve cusps. Pathophysiology: The right ventricle must generate increased pressure during systole to overcome the stenosis, which often leads to dramatic right ventricular hypertrophy. As the right ventricle hypertrophies, its compliance diminishes, which leads to increased right atrial pressures and venous congestion. The jet of blood passing through the stenosis deforms the wall of the main pulmonary artery and results in a poststenotic dilatation. In severe cases, right- sided congestive failure is present. Clinical Findings and Treatment: Affected animals may have a history of failure to thrive and exercise intolerance. Right-sided congestive heart failure may be present and is characterized by ascites or peripheral edema. A prominent ejection-type systolic murmur is present and heard best at the pulmonic valve area. A corresponding precordial thrill is usually present. Jugular distention and pulsations may also be present. Radiographic abnormalities include right ventricular enlargement, an aneurysmal dilation of the main pulmonary artery, and diminished pulmonary vasculature. Animals with moderate or severe pulmonic stenosis will benefit from balloon valvuloplasty or surgical resection. Palliative therapy with diuretics and vasodilators should be initiated if right-sided congestive heart failure is present. Atrial Septal Defects A communication between the atria may be the result of a patent foramen ovale or a true atrial septal defect. During fetal life, the foramen ovale, a flapped oval opening of the interatrial septum, allows shunting of blood from the right atrium to the left atrium, in order to bypass the nonfunctional lungs. At birth, the drop in right atrial pressure causes the foramen ovale to close and shunting to cease. Increased right atrial pressure may reopen the foramen ovale and allow shunting to resume. A true atrial septal defect is a consistent opening of the interatrial septum, which allows blood to shunt from the atrium with the greater pressure. Ventricular Septal Defects Ventricular septal defects are most commonly located in the membranous portion (subaortal) of the septum, near the level of the atrioventricular valves. Tetralogy of Fallot Tetralogy of Fallot is the most common defect that produces cyanosis. It results from a combination of pulmonic stenosis, high ventricular septal defect, right ventricular hypertrophy, and varying degrees of dextroposition and overriding of the aorta. The right ventricular hypertrophy is secondary to the obstruction to right ventricular outflow. The pulmonic stenosis component may be valvular or infundibular, or both. Canine breeds predisposed to tetralogy of Fallot include the Keeshond, English Bulldog, miniature Poodle, miniature Schnauzer, and Wirehaired Fox Terrier. A polygenic trait has been found in the Keeshond. This defect has been recognized in other breeds of dogs and in cats. Pathophysiology: Merck Veterinary Manual - Summary 13  The hemodynamic consequences of tetralogy of Fallot depend primarily on the severity of the pulmonic stenosis and on the size of the ventricular septal defect. The direction and magnitude of the shunt through the septal defect depends on the degree of right ventricular obstruction. If the pulmonic stenosis is mild and right ventricular pressures are only modestly increased, blood will shunt primarily from left to right. When pulmonic stenosis is severe, the increased right ventricular pressures will result in shunting from right to left. Consequences include reduced pulmonary blood flow (resulting in fatigue, shortness of breath) and generalized cyanosis (resulting in polycythemia, weakness). Due to shunting of venous blood into the aorta and consequent hypoxia, the kidneys are stimulated to release erythropoietin, which results in polycythemia ( Polycythemia: Introduction). The increased blood viscosity associated with polycythemia can have significant hemodynamic effects, such as sludging of blood and poor capillary perfusion. Animals with severe polycythemia often have a history of seizures. Clinical Findings and Treatment: Typical historical features include stunted growth, exercise intolerance, cyanosis, collapse, and seizures. A precordial thrill may be felt in the area of the pulmonic valve, and in most cases, a murmur of pulmonic stenosis is present. The intensity of the murmur is attenuated when severe polycythemia is present. Overriding (rightward displacement) of the aortic root, right ventricular hypertrophy, and a ventricular septal defect are evident. β-Adrenergic blockade has been used to reduce the dynamic component of right ventricular outflow obstruction and to attenuate β-adrenergic-mediated decreases in systemic vascular resistance. Increases in systemic vascular resistance will lower the magnitude of shunting. Polycythemia should be controlled by periodic phlebotomy. When the PCV exceeds 68, intervention is indicated. Up to 20 mL/kg of blood can be removed and replaced with a crystalloid solution (eg, lactated Ringer's or saline). The prognosis is guarded. Surgical correction of tetralogy of Fallot is rarely performed due to the attendant mortality and expense. Mitral Valve Dysplasia Congenital malformation of the mitral valve complex (mitral valve dysplasia) is a common congenital cardiac defect in the cat. Canine breeds predisposed are Bull Terriers, German Shepherd Dogs, and Great Danes. Mitral valve dysplasia results in mitral insufficiency and systolic regurgitation of blood into the left atrium. Any component of the mitral valve complex (valve leaflets, chordae tendineae, papillary muscles) may be malformed. Often, more than one component is defective. Pathophysiology: Malformation of the mitral valve complex results in significant valvular insufficiency. Chronic mitral regurgitation leads to volume overload of the left heart, which results in dilatation of the left ventricle and atrium. When mitral regurgitation is severe, cardiac output decreases, which results in signs of cardiac failure. Dilatation of the left-sided chambers predisposes affected animals to arrhythmias. In some cases, malformation of the mitral valve complex causes a degree of valvular stenosis as well as insufficiency. Clinical Findings and Treatment: Affected animals usually display signs of left-sided heart failure, including weakness, cough, and exercise intolerance. A holosystolic murmur of mitral regurgitation is prominent at the left cardiac apex. Thoracic radiographs reveal severe left atrial enlargement. Left ventricular enlargement is also present, and pulmonary veins are congested. Prognosis for animals with clinical signs is poor. Tricuspid Dysplasia Congenital malformation of the tricuspid valve complex is seen occasionally in dogs. Breeds predisposed are Labrador Retrievers and German Shepherd Dogs. Tricuspid dysplasia results in tricuspid insufficiency and systolic regurgitation of blood into the right atrium. Pathophysiology: Malformation of the tricuspid valve results in significant valvular insufficiency. Chronic tricuspid regurgitation leads to volume overload of the right heart, which results in dilation of the right ventricle and atrium. Pulmonary blood flow may be decreased and result in fatigue and tachypnea. As the pressure in the right atrium increases, venous return is impaired, which results in ascites. Clinical Findings and Treatment: Clinical signs correlate with the severity of the defect. Affected animals usually display signs of right-sided heart failure, including jugular distention and pulsation, edema, ascites, tachypnea, and exercise intolerance. Atrial arrhythmias, especially paroxysmal atrial tachycardia, are common and become serious enough to cause death. Thoracic radiographs reveal severe right atrial and right ventricular enlargement. The caudal vena cava may be significantly enlarged. Prognosis for animals with clinical signs is guarded. Periodic abdominocentesis may be needed to control peritoneal effusions. Diuretics, vasodilators, and digoxin may also be indicated. Cardiac Insufficiency And Failure: Overview Merck Veterinary Manual - Summary 14  Heart disease must be distinguished from heart failure. Heart disease refers to a condition in which there is an abnormality of the heart, whereas heart failure exists when the heart is unable to meet the circulatory demands of the body. Most often, the development of clinical signs such as cough, edema, and tachypnea indicate the presence of heart failure. Signs of heart failure may be more pronounced in active animals because their circulatory demands are higher; likewise, signs of heart failure may be delayed in sedentary animals because their cardiovascular systems are rarely challenged. In general, heart failure may occur secondary to decreases in stroke volume or to abnormal heart rates. Decreases in Stroke Volume: Stroke volume (the amount of blood ejected each cycle from either ventricle) may decrease secondary to reductions in preload, impaired contractility, increased afterload, or inadequate valvular function. A significant reduction in preload (analogous to venous return) may result in a decreased stroke volume and consequent heart failure. Examples include shock secondary to hypovolemia or hemorrhage, excessive use of diuretics, pericardial effusion with tamponade, and hypertrophic cardiomyopathy. Impaired contractility decreases stroke volume and can precipitate congestive heart failure; this occurs in dilated cardiomyopathy of large-breed dogs and in cardiomyopathy of overload (myocardial failure secondary to unligated PDA or chronic valvular disease). When there is an increased afterload, a greater than usual deterrent to ventricular emptying exists, which may result in partial ventricular emptying and a decreased stroke volume; this occurs in severe hypertension (pulmonary or systemic) and in aortic or pulmonic stenosis. The AV valves (mitral and tricuspid valves) normally prevent blood from rushing back into the atria during ventricular contraction. When valve function is inadequate or insufficient, blood reenters the atria causing atrial dilation, reducing the amount of forward flow, and consequently decreasing stroke volume. The most common causes of valvular insufficiency are degenerative valve disease (endocardiosis) and infective endocarditis. The pathologic changes can be predicted—when there is insufficiency of the tricuspid valve due to infective endocarditis, tricuspid valvular insufficiency would be expected, as well as right atrial enlargement, vena caval congestion, and ascites. Left-sided Congestive Heart Failure: Left atrial pressure rises whenever left ventricular emptying is encumbered or mitral insufficiency exists. Pulmonary venous flow is impeded and pulmonary venous pressure is increased, which ultimately leads to the formation of pulmonary edema. Cough, which is a consistent feature of left-sided CHF, typically follows activity or is nocturnal. It is initially caused by edema-induced distortion of the pulmonary interstitium. As pulmonary edema worsens, fluid enters the alveoli and airways, causing the cough to increase in intensity and frequency, and rales are present on auscultation. Other signs of pulmonary edema secondary to left-sided CHF include tachypnea, orthopnea (labored breathing while recumbent), and dyspnea. Other clinical signs of left-sided CHF include exercise intolerance, tachycardia, and occasionally weight loss. Right-sided Congestive Heart Failure: An increased in right atrial pressure impedes venous flow from the cranial and caudal vena cava, resulting in systemic venous congestion. Clinically, this is manifested as jugular venous distention, subcutaneous edema, and ascites. The pattern of subcutaneous edema is fairly species-specific—it is uncommon in dogs, generally involves the submandibular and brisket area in cattle, and is seen in the preputial and mammary area in horses. Cats rarely have subcutaneous edema but often develop pleural effusion (hydrothorax). Generalized Congestive Heart Failure: Diseases affecting one side of the heart often precipitate failure of the other side and cause signs of both left- and right- sided CHF. As congestion worsens, left-sided signs predominate due to the severe consequences of pulmonary edema. Diet: A sodium-restricted diet is recommended Diuretics: Diuretics are the mainstay therapy in the management of animals with pulmonary edema. Of the several types of diuretics available (loop diuretics, thiazides, potassium-sparing), the loop diuretics (eg, furosemide) are most commonly used. Furosemide is a potent diuretic that inhibits the resorption of sodium, potassium, chloride, and hydrogen ion from the ascending limb of the loop of Henle—as these ions are excreted, water follows. The dose and frequency of furosemide required depends on the severity of pulmonary edema and the degree of respiratory distress. Side effects of furosemide may include volume depletion and prerenal azotemia, hypokalemia, and metabolic alkalosis (via renal loss of hydrogen). Vasodilators: Vasoconstriction is an important compensatory mechanism that occurs when cardiac output is compromised. ACE inhibitors are indicated in the treatment of mild to severe left-sided CHF in the dog. By reducing vasoconstriction and excessive systemic vascular resistance, ACE inhibitors improve cardiac output and reduce regurgitant fraction when mitral insufficiency is present. The use of vasodilators (eg, enalapril) has become an important part of treatment strategy in animals with heart disease. Clinically, the most significant concern is the development of azotemia secondary to reduced renal perfusion. Although the risk is low, it is recommended that renal function be determined before ACE inhibitor therapy is started. Other ACE inhibitors used (but not approved) include captopril (0.5-1.0 mg/kg, t.i.d.) and benazepril (0.25 mg/kg, s.i.d.). Unlike Merck Veterinary Manual - Summary 15 enalapril and captopril, benazepril is excreted by the liver and may be useful in animals with heart failure and renal insufficiency. Although enalapril and captopril are most commonly used, there are other vasodilators available. Hydralazine directly dilates arterioles presumably by increasing vasodilatory prostaglandins (PGI2). It is specific for arteriolar vasodilation and has little effect on venous tone. Hydralazine decreases pulmonary capillary wedge pressure (similar to left atrial pressure) and increases cardiac index. Hypotension and tachycardia are common side effects, and it is recommended that animals be hospitalized and carefully monitored (blood pressure, electrocardiography) when instituting therapy. If hypotension occurs, hydralazine should be discontinued for 24 hr and then resumed at one-half the previous dosage. Persistent tachycardia should also prompt a reduction in the dosage; occasionally, digoxin or a β-adrenergic blocker are required to control heart rate. Nitroglycerin is a useful venodilator in cases of acute pulmonary edema. By increasing venous capacitance, preload is decreased and blood volume is essentially shifted from the thorax to the abdomen. One major advantage is that because nitroglycerin can be applied to the skin (it is transcutaneously absorbed), administration is not stressful to the animal. The dose of 2% nitroglycerin ointment is 0.3-0.6 cm/kg, applied every 4-6 hr. Gloves should be worn by the person applying the ointment, and care should be taken to avoid contact with the ointment once it has been applied. Side effects are infrequent, but excessive use may result in hypotension, lethargy, and vomiting. Sodium nitroprusside can also be used in acute congestive heart failure because it causes rapid vasodilation. Unlike nitroglycerin, sodium nitroprusside is a balanced vasodilator, causing dilatation of both arterioles and veins. The result is a decrease in both systemic vascular resistance and preload and an increase in cardiac output. Because the half-life is very short, sodium nitroprusside must be administered as a constant rate infusion. It is commonly administered in conjunction with an infusion of dobutamine, a positive inotropic agent (see below). Dobutamine further increases cardiac output and mitigates the hypotensive effects of sodium nitroprusside. Positive Inotropic Agents: These agents increase cardiac contractility and are indicated when myocardial function, specifically contractility, is impaired. Dilated cardiomyopathy and chronic, advanced degenerative valve disease are two common indications in small animals. The digitalis glycosides are the most often used positive inotropic agents. Digoxin and digitoxin increase the intracellular concentration of calcium causing a modest increase in cardiac contractility. Digoxin is the most commonly used digitalis glycoside. Digoxin is renally excreted and therefore should be used with caution in animals with renal insufficiency, if at all. In these animals, digitoxin is the preferred digitalis glycoside because it is metabolized by the liver. Side effects of digitalis are common because the therapeutic index is narrow. Common side effects include depression, anorexia, vomiting, diarrhea, and cardiac arrhythmias. Dobutamine is a synthetic catecholamine that primarily stimulates β1-adrenergic receptors. Through stimulation of these receptors, dobutamine mediates an increase in cardiac contractility. Its positive inotropic effects are much greater than those of the digitalis glycosides. The major indication in veterinary medicine is severe myocardial failure secondary to dilated cardiomyopathy, although it may be used in dogs with degenerative valve disease and concurrent myocardial failure. Dobutamine can cause cardiac arrhythmias—therefore, ECG monitoring is critical during the infusion. Dobutamine also increases conduction of the AV node; therefore, if atrial fibrillation is present, the ventricular response may increase excessively. Other Therapy: Deficiency of L-carnitine has been documented in a family of Boxers with dilated cardiomyopathy, and supplementation resulted in an improvement in cardiac contractility. L-carnitine plays a pivotal role in fatty acid metabolism and myocardial energy production. Compensatory Mechanisms in Congestive Heart Failure When decreased flow or pressure is sensed, there is an immediate withdrawal of parasympathetic tone and activation of the sympathetic nervous system. These changes result in an immediate increase in heart rate and cardiac contractility as well as constriction of arterioles and veins. Decreased blood pressure along with increased sympathetic tone activates the renin- angiotensin-aldosterone axis. Renin is released by the juxtaglomerular apparatus of the kidney and converts angiotensinogen to angiotensin I, an inactive decapeptide. The two terminal amino acids of this peptide are cleaved by angiotensin- converting enzyme (an enzyme found in high levels in pulmonary endothelial tissue) to form angiotensin II, a remarkably potent vasoconstrictor. Angiotensin II also increases thirst, promotes sodium retention by the kidneys, and stimulates secretion of aldosterone by the adrenal cortex, resulting in further sodium and water retention. In the short-term, these compensatory mechanisms are beneficial and help to restore fluid volume and blood pressure. They are life-saving in animals with transient circulatory collapse (eg, hemorrhage) but become maladaptive when stimulated by chronic conditions (eg, heart disease). Sustained activation of the sympathetic nervous system increases myocardial oxygen demand, predisposes the heart to arrhythmias, and may cause myocardial damage (necrosis of myocytes). Persistent sodium and water retention hastens the development of pulmonary edema. Chronic vasoconstriction Merck Veterinary Manual - Summary 16 strains the heart by either increasing afterload or impeding ventricular emptying. As these compensatory mechanisms become deleterious, cardiac output decreases, further stimulating these processes, ie, the “vicious cycle of heart failure.” Therapy of Congestive Heart Failure Medical management of CHF is aimed at reversing or controlling the deleterious effects of the underlying disease. These effects may include pulmonary congestion and edema, cardiac arrhythmias, reduced cardiac output, and excessive vasoconstriction. In severely affected animals, specific medications may be needed to control each of these complications. The Endocardium Infective Endocarditis: Infection of the endocardium typically involves one of the cardiac valves, although mural endocarditis may occur. It is thought that some sort of endothelial defect must be present for infective endocarditis to develop. When the endothelium is partially eroded and underlying collagen exposed, platelets adhere and produce a local thrombus. Blood-borne bacteria may become enmeshed in this thrombic lattice, resulting in a localized infection. This infection, through its own enzymes and host mediators, causes a progressive destruction of the valve, resulting in valvular insufficiency. In dogs, the aortic valve is most commonly affected, resulting in aortic insufficiency. The left ventricle cannot tolerate the constant back flow from the insufficient valve and soon fails. Infective endocarditis of the AV valves (tricuspid and mitral) also occurs but is better tolerated than aortic endocarditis. In horses, the mitral valve is most commonly affected, while the tricuspid valve is most frequently involved in cattle. In cats, infective endocarditis is rare, and there are no breed predilections. In dogs, German Shepherd Dogs and other large-breed dogs are typically affected; there is a significant predilection for males (72%), and the mean age is 5 yr. Bacteria released from the infected valve enter the circulation and colonize other organs; therefore, infective endocarditis can produce a wide spectrum of clinical signs that may be neurologic, GI, urologic, orthopedic, or cardiovascular in nature. A chronic, fluctuating fever is usually present. Shifting leg lameness may occur. Malaise and weight loss are present in almost all cases. If a right-sided valve is affected (tricuspid, pulmonic), ascites and jugular pulsations may be present. A murmur is present in most cases, the exact type depending on the valve involved. When there is aortic endocarditis, a soft diastolic murmur is present, heard best over the left heart base, and arterial pulses are bounding. Mitral endocarditis results in a murmur similar to that caused by degenerative valve disease, ie, a prominent systolic murmur heard best over the left cardiac apex. Bacteria most often isolated from affected small animals include Streptococcus , Staphylococcus , Escherichia coli , and Klebsiella. Streptococcus and Actinobacillus equuli are the most common isolates of horses. A complete blood count often shows a neutrophilic leukocytosis. Radiography demonstrates cardiac chamber enlargement, depending on the location of the involved valve. If the aortic or mitral valve is affected, there will be left atrial and left ventricular dilatation. Evidence of left-sided failure may be seen as an increase in the interstitial densities and an alveolar pattern in the lungs. If the tricuspid or pulmonic valve is affected, right-sided chamber enlargement is expected. Diskospondylitis is a common sequela of infective endocarditis in dogs and is characterized by irregular, lytic vertebral endplates. Echocardiography is the ideal test to definitively diagnose infective endocarditis. The affected valve is easily detected. The height of the R waves may be increased (suggestive of left ventricular enlargement) and the width of the P wave increased (suggestive of left atrial enlargement). Therapy must be directed at controlling the CHF, sterilizing the lesion, and stopping spread of infection. The prognosis is much more favorable when infection is limited to one of the atrioventricular valves. Controlling CHF requires the use of diuretics (eg, furosemide), vasodilators (eg, enalapril), and digoxin if there is a rapid rate, supraventricular arrhythmias, or decreased contractility. Initially, parenteral antibiotics are indicated for 1-2 wk, followed by oral antibiotics for 6-8 wk. Bactericidal antibiotics should be used initially and changed, if needed, based on results of sensitivity studies. The most common combinations are ampicillin and gentamicin or cephalothin and gentamicin (renal function should be monitored). Degenerative Valve Disease (Endocardiosis): This acquired disease is characterized by degeneration and fibrosis of the cardiac valves. As endocardiosis progresses, the affected valve becomes increasingly insufficient. Insufficiency of the mitral valve allows blood to jet back into the left atrium during ventricular contraction, which increases the pressure within the left atrium, which decreases venous flow from the lungs. This results in pulmonary venous congestion and ultimately pulmonary edema. In addition, as the left atrium dilates, the likelihood that atrial arrhythmias (atrial premature contractions, atrial fibrillation) will occur is high, further decreasing cardiac output. The constant jetting of blood from the high-pressure left ventricle physically damages the endocardium of the left atrium and, in chronic cases, may result in left atrial rupture. The decrease in the amount of blood ejected by the left ventricle (cardiac output) forces several compensatory mechanisms into action. The body responds to decreases in cardiac output by increasing sympathetic tone and activating angiotensin-converting enzyme (ACE). On a chronic basis, these compensatory mechanisms become deleterious rather beneficial. Chronic increased sympathetic tone causes sustained tachycardia, which increases the oxygen demand of the heart and predisposes to arrhythmias. ACE Merck Veterinary Manual - Summary 17 activation results in the formation of angiotensin II, which causes sustained arteriolar and venous constriction and release of aldosterone. Vasoconstriction increases the cardiac afterload, hampering ventricular ejection of blood. Aldosterone release results in sodium and water retention and predisposes to pulmonary edema. Endocardiosis is the most common cardiac disease in veterinary medicine. It most commonly affects the left AV (mitral) valve in horses, dogs, and cats, but the disease is uncommon in cats. In horses, degenerative valve disease often affects the aortic valve and consists of valvular nodules or fibrous bands at the free borders of the valve. In most cases in horses, unlike in dogs, clinical signs are uncommon because significant left ventricular volume overload and dilatation do not occur. Echocardiography is used to confirm the diagnosis and allows visualization of the valvular nodules, fibrous band lesions, and valvular prolapse. Treatment is seldom necessary due to the slow progression of the disease and the ability of the horse to tolerate aortic regurgitation. Endocardiosis occurs primarily in small-breed, older dogs, particularly Miniature Poodles, Shetland Sheepdogs, Lhasa Apsos, Dachshunds, and Cocker Spaniels. Radiographically, left atrial enlargement is the characteristic finding. Other changes include enlargement of the left ventricle and the pulmonary veins. The essentials of treatment are to slow the progression of clinical signs early with vasodilators, to control pulmonary edema when it occurs with vasodilators and diuretics, and to reduce the heart rate and increase contractility later in the course of the disease when vasodilators and diuretics begin to lose their effectiveness. Affected dogs can live for years with clinical signs of degenerative valve disease and proper treatment. Stage 1: A soft (grade 1-2) systolic murmur is present, but there are no clinical signs of heart failure and the left atrium is not enlarged radiographically. No cardiac medications are indicated. The owner should be instructed to avoid feeding any foods or snacks high in sodium. Stage 2: A systolic murmur (grade 2-3) is present, there are no clinical signs, yet the left atrium is enlarged radiographically. Vasodilator therapy (eg, enalapril at 0.4-0.5 mg/kg, s.i.d.) will likely be beneficial. Owners should avoid feeding excessive sodium—a diet specifically formulated for older animals is ideal. Stage 3: A systolic murmur (grade 3-4) is present, and there is cough at night and after activity. There is left atrial enlargement radiographically. Vasodilator therapy should be continued (eg, enalapril, dose increased to 0.4-0.5 mg/kg, b.i.d.). Furosemide should be started at 1 mg/kg, s.i.d. to b.i.d., and the lowest effective dose determined. The animal should be fed a diet specifically formulated for older animals. Stage 4: A loud (grade 4-6) systolic murmur is present. There are signs of heart disease, ie, exercise intolerance and cough, through the day. Radiographically, left atrial enlargement is moderate to marked. The heart rate is increased. Enalapril (0.5 mg/kg, b.i.d.), furosemide (1-2 mg/kg, s.i.d. to b.i.d.), and digoxin (0.22 mg/m2) are indicated. A diet moderately restricted in sodium should be part of the therapy. The Myocardium The myocardium is affected by a variety of disease processes, including primary muscle disorders (eg, dilated or hypertrophic cardiomyopathy), degenerative and inflammatory diseases, neoplasia, and infarction. The myocardium is also sensitive to various toxins, including adriamycin, oleander, and fluoroacetate (1080). Myocarditis occurs in all species and may be caused by viral, bacterial, parasitic, or protozoal infection. Canine parvovirus, encephalomyocarditis virus, and equine infectious anemia are viruses with a propensity to cause myocarditis. Myocardial degeneration occurs in lambs, calves, and foals with white muscle disease and in pigs with mulberry heart disease or hepatosis dietetica. Mineral deficiencies (eg, iron, selenium, and copper) can also result in myocardial degeneration. Dilated Cardiomyopathy: This acquired disease is characterized by the progressive loss of cardiac contractility of unknown cause. Several forms of secondary dilated cardiomyopathy exist (cause known); for example, it can be due to a taurine deficiency in cats or induced by adriamycin or parvovirus. As cardiac contractile function is progressively lost, cardiac output decreases. Increased blood volume and pressure within the chambers causes them to dilate, most dramatically evident in the left atrium and left ventricle. In response to the decreased contractility and cardiac output, the sympathetic nervous system and the renin-angiotensin-aldosterone axis are activated. As in degenerative valve disease, these compensatory mechanisms, although initially beneficial, become deleterious when chronically activated. Constant stimulation of the heart by the sympathetic nervous system causes ventricular arrhythmias and myocyte death, while constant activation of the renin- angiotensin-aldosterone axis causes excessive vasoconstriction and retention of sodium and water. In most cases, signs of left-sided congestive heart failure are seen, although signs of right-sided failure (ascites) can develop. Dilated cardiomyopathy is common in large-breed dogs and rare in small-breed dogs (English Cocker Spaniel is an exception). Doberman Pinschers, Great Danes, German Shepherd Dogs, and Labrador Retrievers are particularly at risk. Merck Veterinary Manual - Summary 18 The disease is typically seen in middle-aged dogs, with males affected more than females. The incidence in cats has dropped dramatically since the discovery in 1985 that taurine deficiency was responsible for most cases. Signs include exercise intolerance, inappetence, weight loss, cough, weakness, and syncope. Dogs with predominately right-sided failure usually have a more chronic course, with signs including weakness, exercise intolerance, and ascites. A soft systolic murmur, best heard at the left cardiac apex, is usually present. In addition, a third heart sound or gallop is also frequently present, especially in cats. Echocardiography is the ideal test to definitively diagnose dilated cardiomyopathy. There may be electrocardiographic evidence of left atrial enlargement (P mitrale or widened P waves) and left ventricular enlargement (tall and wide R waves). The occurrence of one or more ventricular premature contractions in a presumed healthy Doberman Pinscher is highly suggestive of dilated cardiomyopathy. The objectives of therapy are to control the congestive state (eg, with diuretics), to improve contractility (eg, with digoxin, dobutamine), and to reduce cardiac stress (eg, with vasodilators). Some animals benefit from supplementation with L-carnitine, taurine, or coenzyme Q10. When congestive heart failure is severe, diuretic therapy should be aggressive, eg, furosemide at 4-6 mg/kg, IV, with a repeat dose 4 hr later. Oxygen supplementation should also be provided, either through an oxygen cage or by nasal insufflation. Nitroglycerin ointment is also indicated. A combination dobutamine and sodium nitroprusside infusion is often beneficial. Vasodilator therapy is definitely indicated; enalapril is the preferred drug and should be administered at 0.5 mg/kg, b.i.d. Other ACE inhibitors, such as captopril and benazepril, can be used but are not approved for use in dogs. L-carnitine will help a few dogs, but a dog deficient in L-carnitine cannot be identified without an endomyocardial biopsy. The prognosis is guarded to poor for most dogs. The prognosis is better for dogs exhibiting predominately signs of right-sided failure, with some surviving for 1-2 yr. Hypertrophic Cardiomyopathy: This is the most common cardiomyopathy in cats. It is characterized by left ventricular hypertrophy in the absence of a precipitating cause (such as hypertension or aortic stenosis) and is typically seen in middle-aged cats. Although contractility is not significantly impaired, the hypertrophic ventricular walls lose compliance and resist filling during diastole (diastolic failure). This increases pressure within the left atrium, causing it to dilate; the pressure is then transmitted to the pulmonary veins, causing pulmonary edema. Stasis of blood often occurs in the markedly dilated left atria, predisposing affected cats to aortic thromboembolism. Middle-aged male cats are primarily affected and often develop acute dyspnea, collapse, or hindlimb paresis. Abnormal heart sounds are frequently present and include soft to prominent heart murmurs and gallop rhythms. Increased bronchovesicular sounds and rales are suggestive of pulmonary edema. Pulses may be weak, normal, or absent if thromboembolic disease is present. Radiographically, there is pronounced left atrial enlargement and variable left ventricular enlargement. Evidence of pulmonary edema is frequently present, and pleural effusion is occasionally seen. Echocardiography is the test of choice and allows confirmation of the disease as well as the need for additional therapy (eg, anticoagulant therapy is most beneficial in cats with severe left atrial enlargement). Contractility is usually within normal limits or excessive. A variety of electrocardiographic abnormalities may be present, including atrial premature complexes, ventricular premature complexes, and ventricular tachycardia. Treatment must control pulmonary edema, improve diastolic function, and reduce incidence of systemic thromboembolism. Furosemide and nitroglycerin are indicated when acute pulmonary edema is present. Diltiazem (7.5 mg, t.i.d.), a calcium-channel blocker, improves diastolic function. Vasodilators are occasionally used. Recently, enalapril has been demonstrated to reduce left ventricular hypertrophy and left atrial enlargement in affected cats. Either aspirin (10 mg/kg, every third day) or warfarin (0.2-0.5 mg, daily) is used to reduce the chance of thrombus formation. Myocardial diseases are infrequently reported in horses. Streptococcus is the most common bacterial cause of myocarditis. Salmonella , Clostridium , equine influenza, equine infectious anemia, Borrelia burgdorferi , and strongylosis have also been incriminated. Deficiencies of vitamin E or selenium are known to cause myocardial necrosis. Cardiac toxins include ionophore antibiotics such as monensin and salinomycin, cantharidin (blister beetle toxicosis), Cryptostegia grandiflora (rubber vine poisoning), and Eupatorium rugosum (white snake root poisoning). These diseases cause typical signs of congestive heart failure—exercise intolerance, tachycardia, and tachypnea. In horses, signs of right-sided heart failure are common and include ascites, venous congestion, and jugular pulsations. A neutrophilic leukocytosis and hyperfibrinogenemia are common. Cardiac isoenzymes (creatine kinase and lactate dehydrogenase) are often increased. Treatment should be aimed at improving cardiac contractility, relieving congestion, and reducing vasoconstriction. Digoxin and dobutamine are used most commonly to improve contractility. Furosemide is indicated to control signs of pulmonary edema. Corticosteroids are often used when cardiac isoenzymes are increased and a viral infection is deemed unlikely. Pericardial Effusion When fluid accumulates within the pericardial sac, the pressure within the sac increases and progressively compresses the chambers of the heart. Because the right-sided chambers have thinner walls than the left-sided chambers, they are compressed to a greater degree. Compression of the right-sided chambers has two major consequences: venous return is Merck Veterinary Manual - Summary 19 significantly decreased, causing jugular venous distension and ascites, and blood flow to the lungs is significantly decreased, causing hypoxia and tachypnea. Once the pericardial pressure equals or exceeds the cardiac chamber pressures, the condition is referred to as cardiac tamponade. If not treated, cardiac tamponade will result in cardiovascular collapse and death. Pericardial effusion (hydropericardium)is uncommon compared with other acquired cardiovascular diseases but is not rare. It occurs in both small and large animals. There are no breed predilections in cats. Labrador Retrievers and Golden Retrievers are the most commonly affected breeds of dogs. Overall, most cases involve large- and giant-breed dogs (90%), and there is a predilection for males (62%). The severity of clinical signs depends on the rate of pericardial fluid accumulation. Historical features include exercise intolerance, inappetence, listlessness, and abdominal swelling. In horses, there is often a history of respiratory tract infection, fever, anorexia, and depression. Physical examination findings include lethargy, jugular venous distention, muffled heart sounds, and occasionally pericardial friction rubs. Ascites is consistently present in affected dogs. The two most common causes are neoplastic (hemangiosarcoma, heart-based tumor) and idiopathic or benign. Less common causes are infectious (feline infectious peritonitis in cats), trauma, chamber rupture, and secondary to congestive heart failure. Cattle most often develop pericardial effusion secondary to traumatic reticuloperitonitis or lymphoma. In horses, septic and idiopathic are the most common types reported. Results of a complete blood count, serum chemistry profile, and urinalysis are usually within normal limits. A mild anemia, neutrophilic leukocytosis, hyperfibrinogenemia, and hyperproteinemia may occur in horses with septic pericarditis and effusion. Cytologic evaluation of the pericardial fluid can be misleading if the effusion is serosanguinous (95% of all canine effusions). In benign effusions, activated mesothelial cells resemble neoplastic cells, and a false positive may be reported. Radiographic findings include an increase in the size of the cardiac silhouette, which takes on a roundish shape (there is a loss of contour caused by the cardiac chambers). Echocardiography is the ideal test to definitively diagnose pericardial effusion. A tumor can be visualized in many cases of neoplastic effusion, but not all. When cardiac tamponade is present, the walls of the right atrium and right ventricle appear to collapse and flutter. The left-sided chambers are often decreased in size secondary to poor return from the lungs. The height of the R waves is often decreased (