Clinical meaning
Ischemic heart disease (IHD) results from an imbalance between myocardial oxygen supply and demand. The NP must understand the determinants of each side of this equation to guide pharmacotherapy. OXYGEN DEMAND is determined by four factors: heart rate (most modifiable and most important determinant), myocardial wall stress (determined by preload, afterload, and ventricular radius via the Law of LaPlace: wall stress = pressure x radius / 2 x wall thickness), contractility (inotropic state), and to a lesser extent, basal metabolic requirements. Tachycardia is particularly detrimental because it both increases demand (more contractions per minute) AND decreases supply (shortened diastole reduces coronary filling time). OXYGEN SUPPLY depends on coronary blood flow (determined by coronary perfusion pressure, which equals aortic diastolic pressure minus left ventricular end-diastolic pressure, and coronary vascular resistance) and oxygen-carrying capacity (hemoglobin concentration, oxygen saturation). Unlike other organs, the myocardium extracts approximately 70-80% of delivered oxygen at rest (the highest extraction ratio of any organ), meaning it cannot compensate for increased demand by extracting more oxygen -- the ONLY way to increase myocardial oxygen delivery is to increase coronary blood flow. Atherosclerotic plaque formation narrows the coronary lumen, limiting the ability to augment flow during increased demand. A 70% stenosis is the threshold where flow becomes inadequate during exertion, producing demand ischemia (stable angina). Plaque rupture with superimposed thrombosis causes acute flow reduction, producing supply ischemia (acute coronary syndrome). The ischemic cascade describes the temporal sequence after flow reduction: diastolic dysfunction occurs first (within seconds), followed by systolic wall motion abnormalities, then ECG changes (ST-segment depression in subendocardial ischemia, ST elevation in transmural ischemia), and finally chest pain -- meaning ECG changes precede symptom onset and patients may have 'silent ischemia.' Anti-ischemic pharmacotherapy targets these determinants: beta-blockers reduce heart rate and contractility (decreasing demand); nitrates reduce preload via venodilation and increase coronary flow via coronary vasodilation (improving supply); calcium channel blockers reduce afterload and, for non-dihydropyridines, heart rate; and ranolazine inhibits the late sodium current to improve diastolic relaxation without affecting hemodynamics.