Pathophysiology of Ischemic Heart Disease

Comprehensive vocabulary flashcards covering the pathophysiology, clinical presentations, hemodynamics, endothelial signaling, and pharmacology of ischemic heart disease and acute coronary syndromes.

Cardiovascular Disease (CVD)

A broad group of medical conditions affecting the heart and blood vessels, driven by physiological and behavioral risk factors that lead to endothelial dysfunction and atherosclerosis.

Myocardial Ischemia

An inadequate supply of blood and oxygen ($O_2$) to a portion of the myocardium, resulting from an imbalance between myocardial oxygen supply and myocardial oxygen demand ($MVO_2$).

Infarct

A small, localized area of dead tissue (necrosis) resulting from the failure or obstruction of blood supply.

$$MVO_2$$

Myocardial oxygen consumption, the major determinants of which are heart rate, myocardial contractility, and myocardial wall tension.

Epicardial Coronary Arteries ($R1$)

Large conduit arteries situated on the surface of the heart that offer trivial resistance to coronary blood flow under normal conditions, but serve as the principal site where atherosclerotic plaques develop.

Prearteriolar Vessels ($R2$)

Intermediate coronary blood vessels that contribute to baseline coronary vascular resistance and dilate alongside $R3$ to compensate when upstream epicardial arteries ($R1$) become narrowed.

Arteriolar and Intramyocardial Capillary Vessels ($R3$)

Microvascular coronary resistance vessels located inside the myocardium that possess a high capacity for vasodilation, reducing resistance to regulate blood flow in response to myocardial metabolic needs.

Critical Coronary Stenosis Threshold

Coronary artery narrowing exceeding $70\%$, at which point microvascular autoregulatory dilation is exhausted, resulting in myocardial ischemia and symptoms even at rest.

Endothelial Nitric Oxide (NO)

An endothelium-derived gas synthesized from L-arginine by eNOS that induces vasodilation and exerts atheroprotective effects by suppressing platelet aggregation, monocyte adhesion, smooth muscle proliferation, superoxide production, and LDL oxidation.

Atheroprotective Flow

Pulsatile, laminar endothelial shear stress that activates transcription factors KLF2, KLF4, and Nrf2, maintaining a quiescent, non-inflammatory endothelial phenotype.

Atheroprone Flow

Disturbed or oscillatory blood flow typically found at vascular branch points that upregulates NF-$\kappa$B, causing endothelial activation and accelerating atherosclerotic plaque formation.

Chronic Stable Angina Pectoris

Chest discomfort triggered by physical exertion or emotional stress due to an accumulation of metabolites from demand ischemia, most commonly caused by fixed atherosclerotic coronary artery disease.

Prinzmetal's (Variant) Angina

A rare type of angina caused by transient vasospasm of large epicardial coronary arteries, occurring almost exclusively at rest and typically associated with underlying atheromas.

Unstable Angina

An acute coronary syndrome involving rest pain or rapidly escalating angina caused by non-occlusive thrombi over a ruptured or fissured plaque, presenting without myocardial infarction or troponin elevation.

NSTEMI

Non-ST-segment elevation myocardial infarction; an acute coronary syndrome where partial coronary artery occlusion causes subendocardial infarction, resulting in elevated cardiac troponins alongside normal ECG, inverted T waves, or ST depression.

STEMI

ST-segment elevation myocardial infarction; an acute coronary syndrome caused by abrupt, complete thrombotic occlusion of an epicardial coronary artery, producing transmural infarction, ST elevation or hyperacute T waves on ECG, and elevated troponins.

Mitochondrial Aldehyde Dehydrogenase 2 (mtALDH2)

The intracellular enzyme responsible for the bioactivation and denitration of nitroglycerin within vascular smooth muscle cells to generate free nitric oxide.

Soluble Guanylyl Cyclase (sGC)

An intracellular enzyme activated by nitric oxide that catalyzes the conversion of GTP to cyclic GMP ($cGMP$), leading to smooth muscle relaxation and vasodilation.

Preload Reduction by Nitrates

The primary beneficial mechanism of nitrovasodilators in angina, wherein venous capacitance vessel dilation decreases blood return to the heart, lowering ventricular preload and myocardial workload ($MVO_2$).

Nitrate Tolerance (Tachyphylaxis)

The loss of hemodynamic and antianginal responsiveness that develops with continuous, uninterrupted exposure to nitrates, likely mediated by reduced bioactivation and diminished nitric oxide release.

Thromboxane $A_2$ ($TxA_2$)

A potent vasoconstrictor and platelet activator released by stimulated platelets during thrombus formation that further enhances platelet activation and promotes potential resistance to fibrinolysis.

Glycoprotein IIb/IIIa (GP IIb/IIIa) Receptor

A platelet surface receptor that undergoes conformational activation to bind multivalent fibrinogen with high affinity, leading to platelet cross-linking and aggregation.

Tissue Factor (TF)

A procoagulant protein exposed upon endothelial disruption and plaque rupture that complexes with factor VIIa to initiate the coagulation cascade, ultimately converting prothrombin to thrombin and fibrinogen to fibrin.