Effects of nitroglycerin on regional myocardial ischemia induced by atrial pacing in dogs.

Abstract

SUMMARYThe exact mechanism or mechanisms by which nitroglycerin exerts its beneficial effect on pacing-induced regional myocardial ischemia has not been ellucidated previously. In an open-chest, anesthetized canine preparation a fixed, flow limiting stenosis was applied to the left anterior descending (LAD) coronary artery and heart rate was increased by atrial pacing. Mass spectrometry was used to measure myocardial oxygen (Pmo 2 ) and carbon dioxide (Pmco 2 ) tensions. Myocardial blood flow was measured by the radioactive microsphere technique. Application of the stenosis resulted in regional decreases in Pmo 2 and increases in Pmcoj of greater magnitude in the subendocardial than in the subepicardial layer. Atrial pacing resulted in a further decrease in Pmo 2 and increase in Pmco 2 as well as a reduction in subendocardial blood flow. Nitroglycerin (TNG) infusion reduced mean arterial pressure 20 mm Hg, resulting in a 14 mm Hg reduction in Pmco 2 in the more ischemic subendocardial layer (P < 0.05). Myocardial blood flow decreased in all regions; however, the magnitude of this decrease was less in the ischemic region. Addition of aortic constriction abolished both the afterload and preload lowering effects of nitroglycerin but improved ischemic zone blood flow. These data demonstrate that nitroglycerin reduces the severity of pacing-induced regional myocardial ischemia primarily by reducing the determinants of myocardial oxygen demand. We found that when these effects are counteracted, improvement in myocardial oxygen supply becomes the dominant mechanism. Circ Res 48: 569-576, 1981 SUBLINGUAL nitroglycerin has been the timehonored therapy for treatment of angina pectoris (Murrell, 1879). Several recent clinical studies have demonstrated that nitroglycerin can be administered safely to patients with acute myocardial infarction by intravenous infusion with consistently beneficial effects on indices of myocardial ischemia (Borer et al., 1975, Come et al., 1975, Flaherty et al., 1976. The ability of nitroglycerin to relieve ischemia in either clinical situation may result from dilating effects on either peripheral arteries or veins, or both, which might decrease determinants of myocardial oxygen demand, or from direct effects on the coronary circulation which might increase myocardial oxygen suppiy-The present study employs a previously wellcharacterized, anesthetized, open-chest canine model to study the mechanism of nitroglycerin's beneficial effect on regional myocardial ischemia, induced distal to a fixed, flow-limiting coronary stenosis by atrial pacing (O'Riordan et al., 1977). This preparation is designed to model a milder degree of reversible ischemia, such as would be present during angina. Previous studies from this laboratory have demonstrated that mass spectrometry can provide a quantitative index of the severity of regional ischemia (Khuri et al., 1975). It was the purpose of the present study to test the hypothesis that nitroglycerin relieves pacing-induced regional myocardial ischemia by a comb...

Haemodynamic factors influencing myocardial ischaemia in a canine model of coronary artery stenosis: the effects of nitroglycerine

“…In our present studies nitroglycerine reduced STsegment elevation in the endocardium more than it did in the epicardium. This accords with the finding that nitroglycerine increases oxygen tension in the endocardium without affecting that in the epicardium (Winbury, 1971) and with the observation of Gerry et al, (1981) that nitroglycerine reduces the elevated subendocardial Pco2 tension in the ischaemic area. This speaks in favour either of a selective arteriolar dilatation by nitroglycerine in the subendocardium or of a preferential effect on the transmural arteries (Winbury, 1971;Weiss, Howe & Winbury, 1973).…”

Postoperative monitoring of myocardial oxygen tension: Experience in 51 coronary artery bypass patients

“…When increased blood flow is adequate to meet the increased oxygen demands, myocardial oxygen tension will be maintained. If the increase in blood flow is sufficient, myocardial oxygen tension will decrease (Gerry et al, 1981). In this clinical study, myocardial oxygen tension decreased in the revascularized regions in the early postoperative days.…”

“…At a constant Po2 level, over a pH range of 7.2-7.9, differences in oxygen current in the various solutions were within 0.2%. This observation is in agreement with the findings of others (Gerry et af., 1981;Horvat et af., 1972;Hultgren et af., 1971).…”

Accurate detection of coronary heart disease by new exercise test.

“…It has been shown that there is a linear correlation between the magnitude of ST segment displacement obtained from epicardial maps and increases in heart rate in anaesthetised dogs with an occluded coronary artery.32 In dogs in whom coronary arteries have been constricted slowly over a period of time it has been shown that the normal increases in myocardial blood flow are drastically reduced in the subendocardial region supplied by the occluded arteries and that this reduction is dependent not only on the coronary perfusion pressure but also on the increases in heart rate and in local extravascular coronary resistance in association with augmented left ventricular enddiastolic pressure. [33][34][35][36] Several studies have shown that the degree of ST segment displacement correlates with the severity of reduction in myocardial blood flow3740 and with the degree of reduction in myocardial oxygen tension.41-43 Thus, from this evidence there should be some relation between ST segment depression, representing the degree of ischaemia (or lowered blood flow and oxygen tension) and heart rate; and the relation should be roughly linear. In the event, the ST/HR slope was surprisingly linear, that is the confidence limits around the regression lines were very small (see Ranges ofmaximal ST/HR slope One remarkable finding in the present investigation is that adjacent ranges of the maximal ST/HR slopes, each range correlating with insignificant, single, double, or triple vessel disease, have shown no overlap; the limits of adjacent ranges are quite separate.…”