The mechanisms of nitroglycerin action: stenosis vasodilatation as a major component of the drug response.

Abstract

SUMMARY The effect of sublingual or intracoronary nitroglycerin (NTG) on luminal caliber in normal and diseased portions of epicardial coronary arteries was determined in 85 lesions from 57 typical patients with ischemic heart disease. Measurements were made from coronary angiograms, using a computer-assisted method and a carefully blinded protocol for analysis of the pre-and post-NTG angiograms. Luminal area in the "normal" portion of the diseased segment and at its maximum constriction and an estimate of flow resistance in the stenosis were computed. Luminal area increased 1.27 mm2 (p < 0.001) in the "normal" regions, an average increase of 18% over the control area. Dilation with NTG depended strongly on vessel size; area increased 35% in normal vessels of 1.6-2.3 mm luminal diameter and only 9% in vessels 4.0-5.0 mm in diameter. Lesions were grouped into four levels of severity by percent stenosis. Minimum luminal area increased 0.35 mm2 (p < 0.01) at the narrowest point in moderate lesions, a 22% area increase, and 0.14 mm2 (p < 0.001) in severe lesions, a 36% area increase. Stenosis dilation resulted in an average 25% reduction (p < 0.01) in estimated stenosis flow resistance in moderate lesions and a 38% reduction (p < 0.001) in severe lesions. A statistically significant resistance reduction of greater than 20% occurred in 15 of 20 severe stenoses; only two of 20 showed no measurable dilation. We reviewed recent literature on hemodynamic responses to NTG and determined that changes of this magnitude are among the largest reported. We conclude that vasodilation of epicardial coronary stenoses is usually a major component of the beneficial response to NTG.We support that conclusion by demonstrating a striking improvement in ischemic left ventricular compliance abnormalities after low-dose intracoronary NTG. NITROGLYCERIN (NTG) affords dramatic relief of angina pectoris in patients with coronary artery disease; yet its mechanisms of action are complex and, in certain respects, controversial. NTG is said to reduce the myocardial oxygen requirement by diminishing systolic wall tension through reduced systemic pressure (afterload) and reduced left ventricular (LV) diastolic pressure and cavity size (preload

Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions.

“…In contrast to traditional dogma regarding fixed stenoses, Brown et al 18 have shown that some coronary stenoses are responsive to vasoactive stimuli. This seems to be particularly true of eccentric lesions in which some portion of the circumference of the stenotic segment is not diseased.…”

Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise.

“…9 In normal subjects it is associated with 15% Control HGP A and intracoronary nitroglycerin despite increases in systemic pressure, heart rate, and double product that were virtually identical to those during the first handgrip test. This nitroglycerin dose has been previously shown to have no effect on systemic hemodynamics, including central venous pressure.20 21 Thus, constriction of severe coronary stenoses, and not increased double product, appears to be the principal mechanism for ischemic left ventricular dysfunction during isometric exercise.…”

“…The infusion was started at the onset of handgrip and continued at a uniform rate until the fourth minute; all measurements were repeated at between 4 and 4.5 min. This dose and rate of administration were selected because they approximated the concentration of nitroglycerin in coronary arterial blood (approximately 120 ng/ml after sublingual administration of 0.6 mg in a patient with 5 liters/min venous return), but was small enough in total dose that it would not effect systemic hemodynamics.20 21 After recovery from the second handgrip test, sublingual nitroglycerin (0.4 mg) was given in the absence of handgrip. Aortic, pulmo-*Stoelting, Inc., Chicago, IL.…”

Differences of intravenous nitroglycerin responses in left ventricular systolic and end‐diastolic pressures and coronary artery diameters during long‐term treatment with cutaneous nitroglycerin patches

“…Nitrates produce an increase in coronary blood flow that is directly related to epicardial coronary artery dilation. [4][5][6] Transdermal nitroglycerin is widely used in the treatment of CAD. However, there is increasing evidence that sustained administration of nitrates can produce Although circulatory tolerance and cross tolerance in terms of blood pressure and heart rate have been demonstrated, limited data are available on nitrate cross tolerance in venous capacitance vessels, which are believed to be the site of predominant nitrate action?.…”