A 60-year-old man comes to the office for evaluation of a 6-month history of intermittent chest pain. He describes substernal tightness and pain that occur when he walks quickly or climbs stairs. The symptoms last about 10 minutes and slowly fade away with rest. These episodes do not happen at rest. The patient has a known history of coronary artery disease with coronary artery bypass grafting surgery 7 years ago. Other medical problems include hypertension and hyperlipidemia. Blood pressure is 140/78 mm Hg and pulse is 78/min and regular. There are no murmurs on cardiac auscultation. Lungs are clear bilaterally. Treadmill stress test is performed. Seven minutes into the test, the patient develops chest pain and the treadmill is stopped. Sublingual nitroglycerin is administered, which almost immediately relieves the patient's pain. What is the predominant mechanism responsible for the rapid pain relief in this patient?
This patient with coronary artery disease has a classic presentation of chronic stable angina (exertional chest pain relieved by rest), with rapid relief of his symptoms following the administration of sublingual nitroglycerin. Nitrates exert their effect by direct vascular smooth muscle relaxation causing systemic venodilation and an increase in peripheral venous capacitance. Their primary anti-ischemic effect is mediated by systemic vasodilation and decrease in cardiac preload resulting in a decrease in left ventricular end-diastolic and end-systolic volume. This, in turn, leads to a reduction in left ventricular systolic wall stress - which reflects afterload and is proportional to (pressure * radius / thickness) - and a decrease in myocardial oxygen demand, resulting in relief of anginal symptoms.
Although nitrates act as coronary vasodilators (via direct relaxation of coronary vascular smooth muscle cells), the beneficial effect of this mechanism is uncertain (Choice A). The coronary arterioles in the area of flow-limiting coronary stenosis are already dilated by innate mechanisms, allowing maintenance of resting blood flow across the stenotic lesion. Nitrate-induced coronary vasodilation paradoxically decreases coronary perfusion pressure across the stenotic lesion by diverting blood flow to arterioles supplying the normal myocardium.
(Choices B and E) Beta blockers and calcium channel blockers exert an antianginal effect partially via a decrease in the heart rate (negative chronotropic effect) or contractility (negative inotropic effect). Nitrates do not have a direct effect on cardiac chronotropy; they may cause decreased inotropy due to decreased preload, but their antianginal effect is thought to be due primarily to a reduction in wall stress.
(Choice D) At low doses (such as those used in sublingual nitroglycerin preparations), nitrates have only a modest effect on arterial and arteriolar dilation and cause minimal or no change in systemic vascular resistance. Higher doses can lead to a drop in systemic blood pressure.
Educational objective:
Sublingual nitroglycerin is used as a first-line agent for rapid relief of symptoms in patients with angina pectoris. The antiischemic effect of nitrates is mediated by systemic vasodilation with a decrease in left ventricular end-diastolic volume and wall stress resulting in decreased myocardial oxygen demand.