BMS 200 - Shock and Ischemic Heart Disease Fall 2024 PDF

BMS 200 – Shock and Ischemic Heart Disease Objectives Categorize edema by pathophysiologic mechanism and common disorders that underly each mechanism Contrast the pathophysiologic mechanisms, situations, and clinical features of hyperemia and congestion Differentiate between hypotension, heart f...

BMS 200 – Shock and Ischemic Heart Disease Objectives Categorize edema by pathophysiologic mechanism and common disorders that underly each mechanism Contrast the pathophysiologic mechanisms, situations, and clinical features of hyperemia and congestion Differentiate between hypotension, heart failure, and shock Describe the pathophysiologic mechanisms and pathological entities that contribute to the four categories of shock Describe the major stages of shock Apply the pathophysiology of the stages and categories of shock to the selection of rational therapeutic interventions Distinguish between the following ischemic heart disease entities: Acute coronary syndromes, stable angina, unstable angina, NSTEMI, STEMI, sudden cardiac death, vasospastic (Prinzmetal) angina Objectives Describe the physiologic parameters that determine the metabolic demands of the heart and relate these to the pathophysiology of ischemic heart disease Describe, where clinically and pathophysiologically useful, the biomedical mechanism for the major risk factors for development of CAD as they relate to atherosclerosis Compare the pathophysiologic situations that cause subendocardial and transmural infarcts Describe the pathophysiologic events that occur during cardiac ischemia Describe the basic epidemiology, clinical features, useful diagnostic procedures, complications, and prognoses of the major forms of ischemic heart disease Briefly describe the pharmacologic mechanism of action and related adverse effects of common medications used to treat ischemic heart disease Hmmmm… A quick case: Your 62-year-old uncle had a stent placed in one of his coronary arteries a year ago, and he states that it has had an excellent impact on his energy and general feeling of well-being. At a family dinner he is sitting at rest, appearing uncomfortable. He takes out a spray canister, sprays it inside his mouth, and massages his chest. You ask him how he’s feeling, and he replies it’s the same old chest discomfort that he’s been dealing with over the past few days. It’s been a little more frequent and he attributes it to stress in the workplace as he transitions to retirement. He states that it’s nothing to worry about, it’s the same discomfort he gets if he works out too hard, and it usually goes away pretty quickly. After 5 minutes he uses the spray again. What are your thoughts about this situation? Edema = excess fluid in interstitial spaces Usual causes: ▪ blood hydrostatic pressure increase Arterial or venous ▪ drop in blood oncotic pressure ▪ increased vascular permeability ▪ blockage of lymphatic flow Many pathologies can cause edema via these basic mechanisms ▪ edema fluid that is low in protein and cells is known as a transudate - Low protein, low cellular content, caused by pressure imbalances. ▪ edema that is high in protein and cells is known as an exudate (typical of inflammation) - High protein, high cellular content, caused by inflammation and vessel damage.  Starling forces - Recall Describe the movement of fluid across capillary walls Explains how fluid moves between blood vessels and surrounding tissues. These forces are a balance between two pushing forces (hydrostatic pressures) and two pulling forces (oncotic pressures).  Starling forces - Recall Variables: 𝐋𝐩 = the “leakiness” of the capillary wall to water ▪ The “inverse” of resistance 𝐏 = hydrostatic pressure 𝛑 = osmotic pressure “cap” = the fluid within the capillary “ISF” = the fluid within the interstitial space 𝛔 = how much protein leaks through the capillary wall 𝐅𝐥𝐮𝐱 = 𝐋𝐩[ (𝐏𝐜𝐚𝐩 − 𝐏𝐈𝐒𝐅 ) − 𝛔(𝛑𝐜𝐚𝐩 − 𝛑𝐈𝐒𝐅)]  Edema and the microcirculation Oncotic pressure - the pull force that draws water into the blood vessels. Mainly created by large proteins. Hydrostatic pressure - the push force that moves water out of the blood vessels into the surrounding tissues. It is generated by the pressure of the blood against the walls of the vessels, especially in the arteries. See notes below for description of each type  How do Starling forces regulate fluid exchange between Movement blood vessels (arterioles and venules) and the surrounding tissue (interstitium).? of Fluid Across Arterial Side (Left) Capillaries Pc (Capillary hydrostatic pressure) is higher than πc (Capillary oncotic pressure). This means that the force pushing fluid out of the capillary (Pc) is stronger than the force pulling fluid back into the capillary (πc). As a result, fluid is driven into the interstitium (surrounding tissue), depicted by the red arrows moving outward. This fluid helps nourish tissues. Venous Side (Right): Pc is now lower than πc The capillary oncotic pressure (πc), driven by proteins like albumin, pulls fluid back into the capillary from the interstitial space (shown by the green arrows). Not all fluid reenters the capillary; some excess fluid is absorbed by the lymphatic system (dotted yellow arrow) to prevent tissue swelling (edema). Edema Causes 1. Increased hydrostatic pressure ▪ can be caused by a generalized global increase in arteriolar blood pressure One significant example is malignant hypertension, where extreme increases in blood pressure overwhelm the normal balance of fluid movement across the capillaries. Can you think of an endocrine cause? Think of an excess of hormones that regulate blood volume and vascular tone. ▪ Usually caused by the factors indicated on the chart on the previous slide Also Decreased venous drainage which can be regional (i.e. a single obstructed vein) or global (i.e. congestive heart failure) can increase hydrostatic pressure Edema 2. Increased sodium and water retention ▪ some people tend to retain more sodium after increases in their diets ▪ pathologies of the kidneys can impair sodium elimination as can decreased perfusion to the kidneys ▪ Endocrine causes: syndrome of inappropriate ADH secretion adrenal cortical pathologies – too much aldosterone  Edema reduced lymphatic drainage ▪ malignancies that infiltrate the lymph nodes ▪ surgeries that resect the lymph nodes ▪ Rarely infections that cause intense fibrosis of lymph nodes and their channels infestation by a parasitic organism – filiariasis ▪ AKA elephantiasis Edema 3. Decreased oncotic pressure ▪ What plasma protein is most responsible for blood oncotic pressure? ▪ Nephrotic syndrome – excess leakage of protein from the glomerulus (renal capillary complex) Protein filters from blood, through glomerular capillary ! protein enters the renal tubules and is excreted in the urine ! decreased oncotic pressure ▪ Hepatic failure ▪ Protein-losing enteropathies or malnutrition Edema 4. Damage to the endothelium or just excessive leakiness can obviously lead to edema ▪ Usually associated with inflammation In tissues that cannot “tolerate” excess interstitial fluid, can be disastrous ▪ i.e. pulmonary edema due to damage to alveolar epithelium and capillary endothelium  Edema General clinical features ▪ tends to be dependent edema – more noticeable in areas of the body that are most inferior to the heart ▪ Many renal diseases can cause a generalized edema that is apparent in areas that contain “looser” connective tissue known as anasarca if generalized different from the massive urticarial edema of anaphylaxis ▪ Pulmonary and brain edema are probably the most severe forms of edema the edema is not just a symptom, but a causative factor in the pathophysiology Unique features of the interaction of the microvasculature and air spaces (lungs) and the inflexible cranial cavity (brain) result in more severe consequences Which is anasarca? Which is angioedema? Hyperemia and congestion Both from locally increased blood volume hyperemia: arteriolar dilation (e.g., at sites of inflammation or in skeletal muscle during exercise) leads to increased blood flow ▪ affected tissues turn red (erythema) because of the engorgement of vessels with oxygenated blood ▪ Example is the return of blood flow to tissue that is warming after being out in the cold  Hyperemia and congestion Both from locally increased blood volume congestion: a passive process resulting from reduced outflow of blood from a tissue (sometimes called passive hyperemia) ▪ can be systemic (heart failure) or local (venous obstruction) ▪ Congested tissues take on a dusky reddish-blue color (cyanosis) due to red cell stasis and the accumulation of deoxygenated ▪ Eventually red blood cells can extravasate, causing hemosiderin deposition in tissues Hemosiderin = degradation product of hemoglobin found mostly within macrophages Congestion Long-standing congestion - chronic passive congestion ▪ Stasis of poorly oxygenated blood causes chronic hypoxia ▪ Result in degeneration or death of cells and tissue fibrosis ▪ Capillary rupture at sites of chronic congestion → small foci of hemorrhage ▪ phagocytosis and catabolism of erythrocyte debris → Accumulations of hemosiderin-laden macrophage  Congestion in individual tissues Pulmonary congestion ▪ Acute: Alveolar capillaries engorged with blood ▪ Chronic: Septa become thickened and fibrotic Alveolar spaces contain hemosiderin-laden macrophages ("heart failure cells") You’ll learn more about pulmonary histology later this semester Hepatic congestion ▪ Acute: Hepatocytes degenerate, sinusoids and venules are distended with blood Those near the hepatic artery circulation undergo less severe hypoxia and develop fatty change Pulmonary congestion Not much air in that lung…  Congestion in individual tissues Fig 7-5 Passive congestion of liver. A. photomicrograph of liver shows dilated centrilobular sinusoids. The intervening plates of hepatocytes exhibit pressure atrophy. B. A gross photograph of liver shows nutmeg appearance, reflecting congestive failure of the right ventricle. C. Late changes in chronic passive congestion characterized by dilated sinusoids (arrows) and fibrosis (note the blue staining of collagen in this trichrome stain). Venous Congestion Type Causes Appearance Clinical Features Pulmonary Left heart failure, Engorgement of Shortness of breath mitral stenosis or pulmonary capillaries (dyspnea), wheezing, regurgitation and venules, alveolar difficulty breathing edema, heart failure with lying flat cells, brown (orthopnea) induration Hepatic Right heart failure, Enlarged liver, Right upper constrictive centrilobular necrosis, abdominal pain, pericarditis nutmeg liver elevated liver enzymes, ascites, peripheral edema, jugular venous distension Deep Veins Blood clot formation Dilated and tortuous Swelling, pain, (DVT), incompetent veins, venous ulcers, tenderness, skin valves potential of thrombus changes formation White vs. Red Infarct White Red Location Organs with a single Organs with a dual blood supply, such as blood supply, such as the kidney or spleen. the lung, intestine, or testis. Main mechanism Arterial occlusion Venous occlusion (atherosclerosis, thrombosis, or embolism) Appearance Pale/ pale yellow Red/ reddish-blue Tissue Feel Dry, firm Wet, congested Damage Abrupt, severe Slow, gradual Tissue-specific infarcts Pulmonary infarcts – complication of a pulmonary embolus in the setting of CHF Difficulty providing oxygenated blood to the larger lung structures (bronchi, bronchioles) Necrosis & hemorrhage in the affected lung Already discussed intestinal infarcts in BMS 150 ▪ Consequence of blocking arterial flow or impaired venous flow (due to obstruction, strangulation volvulus) Splenic infarct ▪ Wedge-shaped, white infarcts located under the capsule Shock final common pathway for several potentially lethal clinical events ▪ severe hemorrhage or dehydration ▪ extensive trauma or burns ▪ myocardial infarction ▪ massive pulmonary embolism ▪ Sepsis and anaphylaxis Shock is a profound hemodynamic and metabolic disturbance in which the circulatory system fails to supply the microcirculation adequately, with consequent inadequate perfusion of vital organs  Categories of Shock Often anaphylactic and neurogenic shock are classified as distributive shock Septic shock is kind of its own entity Shock – a useful classification system Hypovolemic Obstructive ▪ Hemorrhage, ▪ Cardiac tamponade, dehydration, third-spacing pulmonary embolus, of fluid pneumothorax ▪ Too little fluid in vessels ▪ Heart is working, but Distributive blood can’t leave the ▪ Anaphylaxis, spinal shock heart ▪ Too many vessels Septic dilated, not enough ▪ Shock is due to poor blood to keep the blood distribution AND pressure up inflammatory damage Cardiogenic ▪ Heart attack, heart failure, dysrhythmias ▪ Heart isn’t working Shock – a useful classification system Septic shock a severe and potentially life-threatening condition that occurs as a result of sepsis, which is the body's extreme response to an infection. In septic shock, the body's response to infection leads to widespread inflammation, causing significant changes in blood circulation and resulting in a dangerously low blood pressure and inadequate blood flow to vital organs.  Shock - Fatal Shock is fatal primarily due to inadequate tissue perfusion leading to cellular death, multiple organ dysfunction, systemic inflammatory responses, and failure of compensatory mechanisms. The rapid progression and complexity of the condition necessitate early recognition and prompt intervention to improve survival outcomes. Septic shock – simplified pathophysiology There is no one diagnostic test for septic shock – instead a range of scoring systems are used to identify patients that are at higher risk of suffering serious outcomes In general, the following occur (more in Emerg Med): ▪ Dysregulated vascular reflexes ! inappropriate vasodilation and often edema, sometimes due to damage to the endothelium ▪ Higher levels of pro-inflammatory cytokines ! adverse impacts on tissues such as the heart and kidneys ▪ Movement of leukocytes into a wide range of organs ! dysfunction ▪ Inappropriate activation of the coagulation and complement cascades Stages of shock – applies to all causes Stage I – compensated ▪ Tachycardia, but blood pressure is normal Can you describe the physiology behind why tachycardia makes sense, and what physiologic events cause it? Stage II – decompensated ▪ Body is no longer effectively compensating for the reduced flow to tissues ▪ Tachycardia and hypotension ▪ Much more difficult to reverse at this stage Other stages? FYI Stage III – irreversible ▪ If the situation is not corrected very quickly, death will likely ensue – very difficult to treat patients in this stage ▪ High tachycardia or bradycardia, hypotension, evidence of decreased organ function (renal failure, impaired heart function, decreased level of consciousness) ▪ This stage is not always described in texts Multi-organ dysfunction: ▪ As the name suggests, multiple organs “fail” ! lose function and/or become ischemic ▪ Labile BP/hypotension, decreased LOC or coma, physiologic evidence of organ dysfunction Prognosis is poor Shock – (very) general clinical findings hypovolemic and cardiogenic shock: ▪ hypotension ▪ a weak, rapid pulse ▪ tachypnea ▪ cool, clammy, cyanotic skin septic shock: ▪ same as above, but skin may initially be warm and flushed because of peripheral vasodilation Other signs will appear that are more specific for the underlying condition Ischemic Heart Disease Definition: ▪ Supply of blood to the myocardium is inadequate for metabolic demands of the heart Blood supply is either completely blocked or reduced ▪ By far, most common cause is atherosclerosis of the coronary arteries Other causes – aneurysms, autoimmune attack or coronary vessels, strange episodes of vasospasm Epidemiology – 7 million deaths/year are due to ischemic heart disease worldwide – leading cause of death ▪ Every minute, someone in the US dies from myocardial infarction Pathogenesis - IHD Ischemic heart disease develops due to: ▪ Progressive narrowing of coronary arteries ! hypoperfusion of myocardium ! heart failure More on heart failure in e-learning ▪ Sudden occlusion of a major coronary artery resulting in an infarct An atherosclerotic plaque ruptures ! acute clot formation ! blocks the artery or gives rise to an embolus that blocks blood flow further downstream Exacerbated by any situation that increases metabolic activity of the heart ▪ Balance between nutrient/oxygen supply and cardiac metabolic demand  What are factors that acutely affect the heart’s metabolic demands? Heart rate – The faster the heart rate, the more energy used Wall tension – Determined by the volume and pressure within the heart chambers – A dilated, enlarged heart uses more energy than one that is normal size 𝑷 ∙𝒓 – Laplace’s law 𝝈= 𝒉 Contractility – How “hard” the heart contracts at any given time – What intracellular ion? - Intracellular Ca2+  Causes of IHD By far the most common primary cause is coronary atherosclerosis ▪ Many of the other factors exacerbate oxygen delivery or cardiac oxygen consumption Pathogenesis - Influence of atherosclerosis Atherosclerosis is the major cause of ischemic heart disease (90% of cases) – When the lumen of a large coronary artery is reduced by 50 - 75%, there are usually symptoms of IHD during increased activity (i.e. stable angina) – At 80 - 90% reduction, often there are symptoms at rest (i.e. unstable angina) Often, there is more than one cause for ischemic heart disease – i.e. hypertension and a hypertrophic heart in combination with atherosclerotic coronary arteries General Pathophysiologic Concepts A healthy person has substantial coronary flow reserve and myocardial perfusion can increase to five times resting levels with intense exercise ▪ myocardial circulation is mainly controlled by constriction and dilation of small, intramyocardial branches less than 400 μm in diameter ▪ In advanced atherosclerosis of the main epicardial coronary arteries, luminal stenosis decreases blood pressure distal to the narrowed zone Maximal blood flow to the myocardium is not impaired until about 75% of the cross-sectional area of an epicardial coronary artery is compromised by atherosclerosis ▪ Resting blood flow is not reduced until >90% of the lumen is occluded Pathophysiology - Types of IHD presentation Stable angina ▪ If there is a plaque or thrombosis causing occlusion, the obstruction is thought to be stable/unchanging Acute coronary syndromes (ACS) ▪ Unstable angina Could be a thrombus that forms and is broken down constantly over a plaque Could be a very significant (limits a lot of flow, lumen is only 10-20% of regular diameter) stable occlusion Other “rare” conditions, like vasospastic angina, could be the cause ▪ Non-ST elevation myocardial infarction ▪ ST-elevation myocardial infarction Pathophysiology – unstable angina Prinzmetal angina (vasospastic or variant angina) Technically a type of unstable angina, but has a much better prognosis ▪ Caused by coronary artery spasm ▪ Occurs early morning; unrelated to exertion ▪ Does not usually cause infarction ▪ Responds well to vasodilators Nitroglycerine, calcium channel blockers ▪ Typical patient population – younger ( < 60 years) women Adaptations to chronic ischemia in the heart Hypertrophy and changes to the molecular mechanisms of contraction in cardiac myocytes (more on this later) ▪ Ischemic cardiomyopathy Development of coronary collateral circulation ▪ Extensive collateral connections develop in hearts with severe coronary atherosclerosis ! provide enough arterial flow to prevent infarction completely or to limit infarct size if occlusion occurs Pathological pathways during an acute infarct In the heart, the sub-endocardial vessels are the most threatened ▪ The pressure during systole is the highest in the sub- endocardial (inner) small blood vessels, and the subendocardial muscle is the last to relax ▪ The heart ONLY receives oxygenated blood during diastole… especially closer to the interior of the chamber This microcirculatory reality explains the pathological pattern of different types of infarct ▪ Blockade of a major epicardial vessel ! infarcted (dead) tissue across the whole wall ▪ Unstable plaques, partial plaques, global hypoperfusion ! infarcted tissue just in the subendocardium This type of obstruction would likely result in stable angina, not an ACS Severely narrowed lumen could cause angina at rest (therefore These types of obstruction unstable) would likely result in unstable angina or an infarct (ACS) Pathophysiological development of MI The first few minutes: swelling of cells and mitochondria, loss of glycogen ▪ Reversibly injured myocytes show subtle changes of sarcoplasmic edema, mild mitochondrial swelling, and loss of glycogen ▪ “stunned myocardium” = cells that are not dead, but cannot contract After 30 to 60 minutes of ischemia myocyte injury has become irreversible ▪ mitochondria are greatly swollen and deformed ▪ Nuclei show clumping and margination of chromatin and the sarcolemma is focally disrupted ▪ Disruption of cell membranes ! release of intracellular substances into the circulation ▪ Findings of coagulative necrosis Necrosis – mechanisms of injury: ▪ Depletion of ATP ▪ Mitochondrial damage ▪ Calcium accumulation ▪ Oxidative stress / free radicals ▪ Membrane damage ▪ Denatured proteins ▪ DNA damage Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 2-16, p. 45 Mitochondrial damage Mitochondrial membranes can be damaged by free radical attack if levels of cytosolic calcium increase too high in the cell, the MPTP can open ▪ Loss of mitochondrial membrane potential ▪ Releases H+ ▪ Further increase in cytoplasmic calcium Mitochondrial calcium “dumped” into cytosol Increased ▪ Inability to generate cytosolic calcium ! ATP and ultimately MPTP opens necrosis ! leakage ▪ This channel is poorly of H+ and understood.. But calcium important Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 2-18, p. 46  Pathophysiological development of MI Days 2 – 3: ▪ Neutrophils enter necrotic tissue - only gain access at the edge of the infarct, where blood still flows ▪ Interstitial edema and microscopic areas of hemorrhage may also appear ▪ muscle cells are more clearly necrotic, nuclei disappear and striations become less prominent Days 5 – 7: ▪ neutrophils have been replaced by macrophages, myofibroblasts begin depositing collagen (scar tissue) ▪ Dangerous period – the wall is weak  Pathophysiological development of MI Week 1 and later: ▪ Collagen deposition with notable myofibroblasts and macrophages ! ▪ Week 3: mostly scar tissue, new vessels and macrophages have disappeared from the infarct ▪ Later: scar becomes more “solid” as it is remodelled Pathophysiological development of MI What happens if you quickly restore blood flow, before too many myocardial cells have died? Do you “save the day”? ▪ Sort of… Reperfusion injury = damage to cardiomyocytes that occur after blood flow is restored to ischemic tissue ▪ Many myocardial cells will undergo contraction band necrosis when blood flow is restored Contraction band = hypercontracted and disorganized sarcomeres with thickened Z disks. Happens when calcium floods in across disrupted sarcolemma and ROS are generated by damaged mitochondria that suddenly have access to oxygen Can lose some myocardial cells even after blockage is removed (but still advantageous to restore blood flow) Seems that inflammatory damage contributes to reperfusion injury as well Transmural vs. non-transmural infarcts Transmural infarcts ▪ Large, “permanent” occlusion of a coronary artery ▪ Thought to be same entity as an ST-elevation infarct (STEMI) Non-transmural ▪ Can have a variety of pathological patterns ▪ Global hypoxia, many small vessels occluded, transient occlusion ▪ Thought to be the same entity as a non-ST-elevation infarct (NSTEMI)  MI – Typical Vascular Patterns Which vessels are most often involved? – Anterior descending branch of left coronary artery (50%) – apical, anterior, and anteroseptal wall left ventricle infarcts – Right coronary artery (30-40%) – infarct of the posterior basal left ventricle and the posterior 1/3 to 1/2 of the interventricular septum (“inferior” infarct) – Left circumflex artery (15-20%) – lateral left ventricle wall. Vascular territories in IHD IHD – clinical manifestations Asymptomatic Pain – chest pain = angina pectoris – Different patterns of chest pain – referred to left arm/ shoulder, retrosternal, interscapular, can also appear similar to gastro-esophageal reflux – Pain is typically “crushing” or squeezing in character – rarely described as sharp Dyspnea, Fatigue Palpitations Diaphoresis Congestive heart failure symptoms (more later) IHD – Clinical Manifestations How does it usually present? ▪ Acutely: Stable angina Unstable angina Myocardial infarction (two types, ST elevation and non-ST elevation infarcts) Sudden cardiac death ▪ Chronically: Heart failure ▪ Particular type of heart failure sometimes referred to as ischemic cardiomyopathy Ischemic Heart Disease – clinical features Stable angina: ▪ Chest or arm pain (or discomfort) ▪ Reproducibly associated with physical exertion or stress Pattern is consistent with previous episodes ▪ Relieved in a short time period (3 – 20 min) by: Rest Nitroglycerine Ischemic Heart Disease – clinical features Unstable angina – any of: ▪ New onset chest pain/discomfort, or presents differently than before ▪ Occurs at rest or not relieved by nitroglycerine/rest ▪ Is severe, and/or pain is accelerating in intensity (crescendo pattern) Myocardial infarction: ▪ Ischemic heart disease resulting in the death of heart muscle ▪ Type of infarct is determined by ECG and/or pathologic criteria Unstable angina is much more likely to be associated with an infarct than stable angina Together, unstable angina and myocardial infarction are known as acute coronary syndromes (ACS) Ischemic Heart Disease – clinical features Sudden cardiac death ▪ Somewhat poorly named – people can be resuscitated from it and can survive “death” ▪ Criteria are not exact – however, it involves: No acute infarcts A dysrhythmia with sudden onset that is due to long-term coronary ischemia The dysrhythmia is fatal unless aggressive resuscitation measures are undertaken ▪ 90% of the time sudden cardiac death is a complication of long-term IHD Although it is due to long-term coronary vascular disease, it presents suddenly and catastrophically with patient collapse IHD – clinical features Often the pain of an MI is more severe than stable, unstable angina ▪ Many exceptions to this rule, though MIs can masquerade as heartburn Atypical presentations during an MI are not uncommon ▪ Interscapular pain ▪ Discomfort vs. pain ▪ Sometimes dyspnea, acute severe fatigue is the main complaint IHD - Diagnosis ECG – what patterns would you see? ▪ More discussion in dysrhythmias ▪ Can be used for general IHD and for MI Cardiac enzymes ▪ See next slide ▪ troponin (T and I), CK-MB most reliable, specific markers Angiogram Echocardiogram Nuclear medicine imaging ▪ Certain isotopes are taken up more avidly by damaged/ ischemic cardiac tissue IHD - general treatment Treat causes of imbalance between energy supply and demand to the myocardium ▪ ASA – antiplatelet agent, reduces the risk of a life-threatening thrombus developing Prevents existing thrombi from enlarging a number of other anti-platelet agents exist ▪ Antihypertensives (especially ACE inhibitors) ▪ Beta blockers ▪ Calcium channel blockers Reduces contractility, some vasodilate a little ▪ Nitroglycerine Decreases preload, coronary vasodilator, decreases afterload ▪ Good blood glucose and serum lipid control ▪ Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in certain cases Most with stable angina don’t benefit that much from stenting (no survival benefit, does not prevent future MI) so done on a case-by-case basis MI - treatment – NSTEMI – no “clot-busting” drugs like tissue plasminogen activator – STEMI – “clot-busting” drugs can be life-saving – Thrombolytic drugs end in –plase (reteplase, alteplase, used to use streptokinase) – More when we learn about the coagulation cascade – For both, revascularization (angioplasty or putting in a stent) is an effective treatment modality – However, revascularization requires access to a team experienced with the treatment Resuscitation must be immediate or death often occurs when dysrhythmias develop Chronic medications same as those for stable, unstable angina IHD - complications Myocardial infarction: ▪ Death occurs acutely in 25% - 35% of cases due to dysrhythmia (ventricular fibrillation), heart block, heart failure, asystole (cardiac arrest) ▪ Also a high mortality days – months post-infarct Life-threatening dysrhythmias Cardiac rupture – highest risk at 3 – 7 days post-MI due to coagulative ! liquiefactive necrosis in the wall of the myocardium or at the attachment point of a papillary muscle Poor wall motion ! clot development (more later) Pericarditis