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

Abstract

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. ...

Temporal fluctuations in regional myocardial flows

“…The variations that occur in the myocardium in metabolic rate (Griggs et al 1972, Dunn andGriggs 1975), oxygenation (Gamble et al 1974;Schubert et al 1978;Weiss and Sinha 1978), and myocardial fiber shortening (LeWinter et al 1975) have become generally recognized. Similarly, the spatial heterogeneity of regional myocardial blood flow has been clearly demonstrated with indicator dilution methods (Bassingthwaighte et al 1972;Rose and Goresky 1976;Roselli and Harris 1979) and with the microsphere technique (Yipintsoi et al 1973;Falsetti et al 1975;Marcus et al 1977;Sestier et al 1978).…”

Rate of rise of myocardial PCO2 during early myocardial ischemia in the dog.

“…Following coronary artery occlusion, myocardial lactate becomes elevated within 15 seconds, and creatine phosphate is decreased by this time; ATP begins to fall within 30 seconds (Dunn and Griggs, 1975). A rise in extracellular potassium has been reported to occur within 30 seconds (Hill and Gettes, 1977), and the earliest pH decrease was found at 15 seconds (Benzing et al, 1971/72).…”

Myocardial blood supply by left ventricle-to-coronary artery channel: An old idea revisited

“…Under these anaerobic circumstances, h-oxidation, citric acid cycle and electron transport chain cannot take place (Fig 4). Several studies have shown that during ischemia differences exist in metabolism between the subepicardium and subendocardium, resulting in a more rapid depletion of energy stores in the subendocardium compared to the subepicardium, in analogue to the perfusion differences found with microspheres [20][21][22]. These differences in metabolism can be explained by several reasons.…”