Published on 07/02/2015 by admin
Filed under Anesthesiology
Last modified 07/02/2015
This article have been viewed 2439 times
Suneerat Kongsayreepong, MD
Nitroglycerin (glycerol trinitrate) is metabolized to NO in the vascular smooth-muscle wall and acts to stimulate cyclic guanosine monophosphate (cGMP) production. Increased cGMP leads to the reduction of cytosolic Ca2+, dephosphorylation of the myosin light chain, and smooth muscle relaxation and vasodilation. Because sulfhydryl groups are needed to produce the NO, vascular tolerance can occur when an excessive number of sulfhydryl groups are metabolized by prolonged exposure to nitroglycerin. Nitroglycerin is reported to have greater effects as a venodilator because of greater uptake in veins, as compared with arteries.
Metabolism of nitroglycerin occurs in the liver by hepatic glutathione organic nitrate reductase; inactivated metabolites are excreted by the kidney. Nitroglycerin, with a half-life of 1.9 to 2.6 min, also appears to be taken up by and metabolized in the endothelium of vessel walls.
Because of the aforementioned greater uptake of nitroglycerin by the venous endothelium, nitroglycerin acts primarily on venous capacitance vessels, causing peripheral and splanchnic pooling of blood, decreased preload, decreased cardiac ventricular wall tension, and decreased heart size. With increased concentrations of nitroglycerin, relaxation of arterial vessels occurs, first affecting conductance vessels and then the smaller resistance vessels.
The effect of nitroglycerin on cardiac performance depends on the patient’s underlying cardiac status. In patients with a normal or low ventricular filling pressure, cardiac output may decrease because of inadequate preload. In those with congestive heart failure (CHF), cardiac output increases as a result of decreased preload, reduced systolic wall tension, and, at higher doses of nitroglycerin, a decrease in afterload. For similar reasons, nitroglycerin, at high doses, also improves cardiac output in patients with mitral regurgitation. In patients with coronary artery disease, nitroglycerin causes decreased wall tension and decreased myocardial O2 demand, which, in turn, results in increased myocardial contractility and cardiac output.
Myocardial blood flow is affected indirectly via hemodynamic changes and directly by coronary arterial dilation. Coronary perfusion increases more from the lowering of left ventricular end-diastolic pressure than from improved flow during diastole. A decrease in left ventricular end-diastolic pressure also reduces extrinsic tissue compression of coronary vessels in the subendocardium. Nitroglycerin is a potent epicardial coronary vasodilator in both normal and diseased vessels. Therapeutic doses of nitroglycerin dilate large coronary arteries but not coronary arterioles, improving collateral and subendocardial blood flow to ischemic areas. Nitroglycerin produces less coronary steal than do agents that produce intense vasodilation of the small coronary resistance vessels. High doses of nitroglycerin (9-32 μg·kg−1·min−1) cause direct coronary arteriolar vasodilation, overriding any coronary autoregulation. Part of the action of nitroglycerin on coronary vasodilation may involve its effects on stimulating the production and release of prostacyclin.
Nitroglycerin causes vasodilation of pulmonary arteries and veins, resulting in a decrease in right atrial, pulmonary artery, and pulmonary artery occlusion pressure. Nitroglycerin may reduce the pulmonary artery hypertension associated with various disease states and congenital heart disease. Nitroglycerin also dilates renal arteries, cerebral arteries, and cutaneous vessels. Blood flow to the kidney and brain may decrease if adequate systemic blood pressure is not maintained.
The cause of the antianginal effects of nitroglycerin is multifactorial. The use of nitroglycerin reduces the preload and systolic wall tension, resulting in decreased myocardial O2
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