Nitroglycerin and Heterogeneity of Myocardial Blood Flow REDUCED SUBENDOCARDIAL BLOOD FLOW AND VENTRICULAR CONTRACTILE FORCE

Forman, Robert; Kirk, Edward S.; Downey, James M.; Sonnenblick, Edmund H.

doi:10.1172/jci107255

Cited by 86 publications

(12 citation statements)

References 15 publications

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“…Both studies supported the concept that the subendocardium is more vulnerable to hypoxia than is the subepicardium because of a transmural gradient in myocardial tissue pressure (5, 6) which imposes a nonuniform type of extravascular resistance on the coronary circulation. Additional studies from this (1, 3,4,8) and other laboratories (7,(20)(21)(22)(23)(24)(25) have added considerable support to the hypothesis that the greater vulnerability of the subendocardium to hypoxic injury is due to a nonuniform distribution of myocardial blood flow in the underperfused ventricle.…”

Section: Discussionmentioning

confidence: 81%

Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog.

Dunn¹,

Griggs²

1975

Circulation Research

120

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To determine whether transmural metabolite gradients develop in the contracting, ischemic left ventricle due to factors other than a nonuniform distribution of myocardial blood flow, right and left coronary artery inflow was completely stopped with vessel occluders in open-chest dogs for 15 or 30 seconds before a transmural myocardial tissue sample was obtained for regional analysis of creatine phosphate, adenosine triphosphate (ATP), and lactate. Heart rate was controlled, and the decline in left ventricular systolic pressure during the period in which coronary blood flow was stopped was attenuated by aortic constriction. Studies were also performed in dogs that were (1) pretreated with propranolol, (2) subjected to ventricular fibrillation, and (3) volume loaded. Control studies revealed no transmural metabolite gradients in the normally perfused ventricle, but creatine phosphate was slightly lower in the inner region than it was in the outer and middle ventricular wall regions. With coronary blood flow stopped for 30 seconds, a significant lactate gradient, increasing from the outer to the inner region, was present. Propranolol-treated dogs with their coronary blood flow stopped for 30 seconds also exhibited a lactate gradient, but dogs with ventricular fibrillation and their coronary blood flow stopped for 30 seconds did not. Volume-loaded dogs with their coronary blood flow stopped for only 15 seconds had a significant lactate gradient. Reciprocal gradients occurred in creatine phosphate but not in ATP. The findings suggest that the contracting ventricle uses energy unevenly and that in myocardial ischemia one of the factors causing greater subendocardial vulnerability is a greater energy need in this region.• Previous studies from this laboratory have shown that metabolic changes occurring in the left ventricle because of inadequate coronary blood flow are greater in the subendocardium than they are in the subepicardium (1-4). This difference has been attributed primarily to nonuniform systolic compression of the coronary vessels (5, 6) which results in a greater impairment of subendocardial blood flow than it does of subepicardial blood flow (7,8). However, the possibility also exists that other factors, such as a higher subendocardial energy requirement (9-12), a greater capacity of subendocardial tissue cells for glycolysis (13,14), or greater subendocardial beta-adrenergic stimulation, contribute to the uneven metabolic response. The primary purpose of the present study was to investigate these possibilities in open-chest dogs by examining regional metabolite levels in the left ventricle after blood flow had been completely stopped in both the left and right coronary arteries for a brief but metabolically significant interval of time. Heart rate was controlled, and the decline in This work was supported by U. S. Public Health Service Grant HL 11876 from the National Heart and Lung Institute and by the Missouri Heart Association.Received April 7, 1975. Accepted for publication June 30, 1975. ...

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Section: Discussionmentioning

confidence: 81%

Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog.

Dunn¹,

Griggs²

1975

Circulation Research

120

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“…Initially, mean EST increased slightly from 35 with a reduction in collateral resistance below base line in all eight animals (Fig. 1).…”

Section: Resultsmentioning

confidence: 90%

“…during partial coronary occlusion (3,19,32,33) and also before a short period of complete occlusion (34), caused a redistribution of flow toward the endocardium. Intracoronary injection of nitroglycerin caused a shift in the opposite direction (35). In the nonischemic heart, nitroglycerin resulted in no change in transmural flow (36).…”

Section: Discussionmentioning

confidence: 98%

Effect of nitroglycerin and dipyridamole on regional left ventricular blood flow during coronary artery occlusion.

Becker

1976

J. Clin. Invest.

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A B S T R A C T Coronary vasodilators have been vari-ously reported to increase, decrease, or have no effect upon blood flow to ischemic myocardium. Consequently, the effects of two different types of dilators, nitroglycerin (TNG) and dipyridamole, were studied with radioactive microspheres in open-chested dogs after coronary artery ligation. Given as a bolus i.v. injection, 0.4 mg TNG resulted in an increase in blood flow to nonischemic areas of myocardium and a preservation of flow to ischemic regions, despite a fall in blood pressure. 5 min later blood pressure and nonischemic flow were back to base line, and a small selective increase in flow to ischemic myocardium was found (0.15-0.18 ml/min per g, P < 0.05). During an 0.2 mg/min infusion of TNG, and also after 1 mg/kg i.v. dipyridamole, ischemic flow was maintained in the face of a 20-30%o reduction in blood pressure. In this setting, nonischemic flow was unchanged during TNG and doubled after dipyridamole. With the addition of methoxamine in both dilator groups, blood pressure retumed to base line while flow to ischemic areas increased above base-line values (TNG, 0.16-0.20 ml/min per g, P < 0.01; dipyridamole, 0.18-0.31 ml/min per g, P < 0.05). Epicardial ST segment elevations increased during TNG infusion and were unchanged after dipyridamole, but with addition of methoxamine, ST segments became less elevated in both drug groups, concomitant with the observed increase in collateral blood flow. These data indicate thaA both types of coronary vasodilators, when used in conjunction with methoxamine to support blood pressure, reduce collateral resistance, increase collateral flow, and reduce epicardial ST-segment elevations.

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“…8 (14,21,(23)(24)(25)(26), radioisotopic determination of collateral flow (15,23,24,(27)(28)(29)(30), and microsphere determination of flow distribution (31 (5), and therefore the special conditions of our protocol must not be overlooked. Collateral vessels in the dog heart are often epicardial, whereas these vessels tend to be intramural in man (38 (18). Therefore coronary vasodilatation alone could be deleterious by initiating a steal.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Nitroglycerin on Coronary Collaterals and Myocardial Contractility

Cohen¹,

Downey²,

Sonnenblick³

et al. 1973

J. Clin. Invest.

Self Cite

132

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A B S T R A C T Nitroglycerin (TNG) causes a prolonged dilatation of coronary collaterals. To demonstrate a functional significance of this dilatation we measured the effect of TNG on myocardial contractile force in dogs 2j-4 wk after the left anterior descending coronary artery (LAD) had been embolized in closed-chest animals. Development of collaterals was documented by angiography. Via a left thoracotomy the main left coronary artery (LCA) and LAD distal to the embolized plug were cannulated. Coronary flow and perfusion pressure were recorded. Contractile force was measured with gauges sutured to epicardial areas supplied by the left circumflex coronary artery (LCf) and occluded LAD. Coronary perfusion pressure in the LCA was gradually decreased until the contractile force recorded by the LAD gauge diminished while the LCf gauge was unaffected. Under these conditions, with coronary perfusion pressure held constant with the aid of a Starling resistance, TNG (18 ,g) injected into the LCA increased peripheral LAD pressure by 3-12 mm Hg and contractile force in the LAD region by 36% (range 20-90%), returning it to near-normal levels, while having minimal effect in the LCf area. These changes persisted for 5 min. When LCf and LAD areas were both ischemic, intracoronary TNG had minimal effect on peripheral LAD pressure and contractile force. Thus, TNG causes prolonged dilatation of coronary collaterals and presumed increased collateral flow with subsequent enhancement of myocardial contractile force in ischemic areas. This effect is seen only when ischemia is limited to an area supplied by the collaterals. When the whole heart is This study was presented in part at the 22nd Annual

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Nitroglycerin and Heterogeneity of Myocardial Blood Flow REDUCED SUBENDOCARDIAL BLOOD FLOW AND VENTRICULAR CONTRACTILE FORCE

Cited by 86 publications

References 15 publications

Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog.

Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog.

Effect of nitroglycerin and dipyridamole on regional left ventricular blood flow during coronary artery occlusion.

The Effects of Nitroglycerin on Coronary Collaterals and Myocardial Contractility

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