Ischemic Heart Disease

• British physician William Heberden first described ischemic heart disease symptoms in 1772.
• This condition arises from an imbalance between myocardial oxygen supply and demand, usually due to coronary artery atherosclerosis.
• Angina pectoris is the most common presentation, referring specifically to chest discomfort from this imbalance.
• Ischemic heart disease affects millions in America, considered the leading cause of death in industrialized nations.
• Ischemic heart disease exhibits variable clinical presentations, spanning exertional symptoms to silent ischemia (no clinical manifestations).
• Silent ischemia is when it occurs with no clinical manifestations

Clinical Definitions

• Ischemic heart disease is a condition where myocardial oxygen supply and demand imbalance leads to myocardial hypoxia and waste accumulation.
• Angina pectoris marks uncomfortable sensations in the chest and neighboring structures from myocardial ischemia.
• Stable angina presents a chronic pattern of transient angina pectoris, triggered by physical activity or emotional stress, and diminishes with rest; temporary ST segment depression may appear, without lasting myocardial damage.
• Variant angina manifests as typical anginal discomfort usually at rest because of coronary artery spasm instead of oxygen demand increase; transient ST segment shifts, mainly ST elevation, are often seen (also known as Prinzmetal angina).
• Unstable angina is a pattern of increasing angina episode frequency and duration, produced during less exertion or while resting; high likelihood of advancing to myocardial infarction without treatment.
• Silent ischemia is characterized by asymptomatic episodes of myocardial ischemia, detectable through electrocardiogram and other laboratory techniques.
• Myocardial infarction is regional myocardial necrosis often caused by sustained blood supply cessation; mainly caused by acute thrombus formation within a coronary atherosclerotic stenosis; may be the initial sign of ischemic heart disease, or follow a history of angina pectoris.

Determinants of Myocardial Oxygen Supply and Demand

• Balance is maintained.
• Myocardial oxygen supply depends on oxygen content and coronary blood flow.

Myocardial Oxygen Supply

• Hemoglobin levels and systemic oxygenation determine oxygen content.
• Coronary blood flow is dynamic, supplying metabolic needs.
• Coronary artery flow (Q) directly corresponds to perfusion pressure (P) and inversely to vascular resistance (R).
• Unlike other arterial systems the blood flow takes place during diastole.
• The systolic flow gets impaired by the compression of the small coronary.
• The relaxed myocardium does not compress the coronary vasculature, and diastolic coronary flow goes unimpeded.
• Aortic diastolic pressure (approximated by difference between aortic and left ventricular diastolic pressures) represents perfusion pressure in the coronaries. Reduced aortic diastolic pressure diminishes myocardial oxygen.
• Coronary vascular resistance is either external compression or modulated by intrinsic coronary tone.
• External compression relates to intramyocardial pressure and is greatest during systole, particularly in the subendocardium, making it vulnerable to ischemic damage.

Intrinsic Regulation

• The heart cannot increase oxygen extraction, so blood flow must increase.
• Autoregulation, influenced by local metabolites, endothelium-derived substances, and neural innervation mediates increased blood flow.

Metabolic Factors

• Local metabolite accumulation affects vascular tone.
• During hypoxia, aerobic metabolism and ATP production are impaired, leading to the accumulation of ADP and AMP, which degrade to adenosine.
• Adenosine acts as a vasodilator by binding to receptors on vascular smooth muscle, decreasing calcium entry, and increasing blood flow. Lactate, acetate, hydrogen ions, and carbon dioxide also have a similar function.

Endothelial Factors

• Endothelial cells produce vasoactive substances that regulate vascular tone including vasodilators such as nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF). Endothelin 1acts as the vasoconstrictor.
• NO regulates vascular tone by diffusing into arterial smooth muscle, which relaxes neighing arterial cells by a cGMP-dependent mechanism.
• The production of NO is stimulated by substances like acetylcholine (ACh), thrombin, products of aggregating platelets eg serotonin or even blood flow shear stress. The prostacyclin causes relaxation of the walls by a cyclic AMP-dependent mechanism.
• Like NO, EDHF hyperpolarizes and relaxes vascular smooth muscle.
• Stimulation results in coronary vasoconstriction. However, catecholamine stimulation also increases oxygen consumption via heart rate and contractility (β₁-adrenergic effect) resulting in increased production of local metabolites.
• Catecholamine stimulation leads to net coronary vasodilatation.

Myocardial Oxygen Demand

• The demands are (1) ventricular wall stress, (2) heart rate, and (3) contractility.
• Small oxygen amounts generate basal energy for cardiac electrical and metabolic depolarization.
• Wall stress relates to intraventricular pressure (P), ventricular radius (r), and wall thickness (h), which augment myocardial oxygen consumption.
• Wall stress reduces myocardial oxygen consumption, resulting in a lower stress, and thinner walls.
• Heart rate increases the oxygen requirement.

Pathophysiology

• Atherosclerotic plaques narrows vessel lumen, limiting blood flow.
• Reduction in blood flow results from both fixed vessel narrowing and abnormal vascular tone.
• The hemodynamic significance relates to fluid mechanics and vascular anatomy.
• Vascular resistance relates to vessel geometric measurements known as poiseuille law,

Fixed Vessel Narrowing

• Vascular resistance depends on length/radius.
• Stenotic lesion depends on length and reduction degrees.
• Coronary arteries have proximal segments and distal vessels. proximal segments that are overt atherosclerotic results in stenotic plaques. The distal vessels adjust vasomotor tone in response to metabolic needs.
• Resistance vessels increase to meet increasing oxygen demand, then dilate sufficiently. They function as reserve vessels or have proximal stenosis.
• Stenosis depends on epicardial narrowing level and distal vessel vasodilatation degree.
• Stenosis <60% the potential blood flow remains unaltered. Resistance vessels are able to dilate in response to exertion. Stenosis reduces ~70% blood flow.
• Resting flow is normal.
• Maximal blood flow decreases with full resistance vessel dilation.
• In physical exertion, the myocardial ischemia results if the stenosis compromises lumen vessel by ~90%.
• Even maximal vasodilation occurs in the resistance vessels. Then the blood flow doesn't meet basal requirements and ischemia may develop from rest.

Endothelial Cell Dysfunction

• It reduces oxygen supply in chronic CAD.
• Endothelial cell contributes to two ways; improper arterial constriction and loss of normal properties.
• The factors, physical activity, and stress, all produce arteries vasodilation. In normal coronary arteries, the relaxation of NO outweighs catecholamines because they have vasoconstrictors action on the arteriel muscle that makes vasodilation. Vasoconstriction happens.
• Attenuated endothelium couples vascular tone to metabolic
• Endothelium-dependent in noted even before lesions are developed.
• Vascular constrictions appears to be coronaries. Plaque disrupts platelets, thrombus are fromed. The actions of the products will vasodilator NO but constricting actions takes place when endothelium dysfunction occurs.

Other Causes of Myocardial Ischemia

• There could an reduction of oxgen supply, or decreased content in blood. Such as low oxyen levels (Hypoxia). Or bleeding causes less hemobolin which leads to less of Oxygen supply. A prfound increases of myocardia oxygen and imbalance results in ischmemia this can occue with rapid tachacardiac, acute hypertension or serve actic stenosis.

Consequence of Ischemia

• Myocytes switch to anaerobic metabolism, impairing contractile protein interaction and causing both systolic contraction and diastolic relaxation.
• The elevation of LV (via the left atrium and pulmonary veins) to precipitate pulmonary hypertension increases myocardial oxygen.
• Local metabolites, such as lactate accumulate.
• The myocardium fate is affected. Myocardial episodes can result in reversible myocyte function.
• Stunned myocardium refers to the tissue not yet recovered. calcium overload and accumulation.
• Hibernation: The special imaging can find out the myocardial the that be under take can restore some fluncation with the blood and infarct ones will never.

Ischemic Syndromes

• The following depends on physioldic.
• Pathophysiologic Findings present In Stable Agina Lumen was narrowed by plaque, this inappropriate constrictuion. unstable shows plaque rupture Plaque aggregation formation all reduce coronary supplies. Vanit agina hows no ouver plaque inten vasospasm this cuases increase oxygen.

Stable Angina

• Chronic manifests a chest discomfort emotions . Is cause by obstrutive plaque in he one or two.
• The patients have low demands. Exercise is like sympthatic system the rate of blood pressure is hihg.
• Pantients lack the supply so iscmeia results. Then symptoms presist unil the increased demand allivated.

Unstable Agina

• If it happnes it know as unsable Angia which a pre cer to MI such sympoms are.
• These are aruptured plaue lets thromosilsis these are describe chater seven.

Varient Angina

• This synonm is also knows as prinze. Is a small group of focal artery Spasms. This all cause reduction supplie and result in angina to supply and rest.

Silent Ischemia

• Cardiac happens that not feel can be silet ischemais is pree. A range may be 20 to 50 % in these type. The oyl mansfer. The eepsiode may only be the one may happen of CAD
• the unmanefactrue of ilicent may become more concern. It may be common among eldery, diabetes, and in wmen.

Microvascular Angina

• refer to the clinical syndrome of angina pectoris in the absence of significant atherosclerotic coronary stenoses on coronary angiography,. In the case some show lab sign of schemima
• is not clear they may be small may or may not dialte. has a better rate than evert diease but a poorer genral.