Effect of Coronary Blood Flow on Glycolytic Flux and Intracellular pH in Isolated Rat Hearts

The rate of coronary blood flow was varied in isolated working rat heart preparations to determine its influence on the rate of glucose utilization, tissue high-energy phosphates, and intracellular pH. A 60% reduction in coronary blood flow resulted in a 30% reduction in oxygen consumption, an accelerated rate of glucose utilization, lower tissue levels of high-energy phosphates, and higher tissue levels of lactate and H+. Ventricular performance deteriorated as reflected by a decrease in heart rate and peak systolic pressure. Further reductions in coronary blood flow resulted in inhibition of glycolysis, a greater decrease in tissue levels of high-energy phosphates, and higher tissue levels of both lactate and H+. These changes in glycolytic flux, tissue metabolites, and ventricular performance were proportional to the degree of restriction in coronary blood flow. The importance of coronary blood flow and washout of the interstitial space in the maintenance of accelerated glycolytic flux in oxygen-deficient hearts is emphasized. It is concluded that acceleration of ATP production from glycolysis can occur only in the marginally ischemic tissue in the peripheral area of tissue supplied by an occluded artery. The central area of tissue which receives a low rate of coronary blood flow will have a reduced rate of ATP production due to both a lack of oxygen and an inhibition of glycolysis.

[1]  L. Opie.  Metabolic Response during Impending Myocardial Infarction: I. Relevance of Studies of Glucose and Fatty Acid Metabolism in Animals , 1972, Circulation.

[2]  M. Oliver.  Metabolic Response during Impending Myocardial Infarction: II. Clinical Implications , 1972, Circulation.

[3]  Edwards Ws,et al.  TISSUE NECROSIS AFTER TEMPORARY CORONARY ARTERY OCCLUSION. , 1963 .

[4]  L. Opie.  Substrate utilization and glycolysis in the heart. , 1971, Cardiology.

[5]  T. W. Moir,et al.  Effect of Left Ventricular Hypertension, Ischemia and Vasoactive Drugs on the Myocardial Distribution of Coronary Flow , 1967, Circulation research.

[6]  L. Becker,et al.  Effect of Ischemia and Antianginal Drugs on the Distribution of Radioactive Microspheres in the Canine Left Ventricle , 1971, Circulation research.

[7]  L. Opie.  Metabolism of the heart in health and disease. I. , 1968, American heart journal.

[8]  R. Jennings.  Early phase of myocardial ischemic injury and infarction. , 1969, The American journal of cardiology.

[9]  M. N. Levy,et al.  Collateral Blood Flow to the Myocardium as Determined by the Clearance of Rubidium86 Chloride , 1961, Circulation research.

[10]  L. Opie.  Metabolism of the heart in health and disease. Part I , 1968 .

[11]  A. Liedtke,et al.  Metabolic responses to varying restrictions of coronary blood flow in swine. , 1975, The American journal of physiology.

[12]  P. J. Randle,et al.  Regulation of glycogenolysis in muscle. Effects of glucagon and anoxia on lactate production, glycogen content, and phosphorylase activity in the perfused isolated rat heart. , 1963, The Journal of biological chemistry.

[13]  J R Neely,et al.  The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart. , 1972, The Biochemical journal.

[14]  Hans Ulrich Bergmeyer,et al.  Methods of Enzymatic Analysis , 2019 .

[15]  J. Scheuer,et al.  Metabolism of glucose by the ischemic dog heart. , 1967, The American journal of physiology.

[16]  J. Scheuer.  The effect of hypoxia on glycolytic ATP production. , 1972, Journal of molecular and cellular cardiology.

[17]  J. H. Fisher,et al.  Recovery of the dog's heart after varying periods of acute ischemia. , 1953, Surgical forum.

[18]  W. Edwards,et al.  TISSUE NECROSIS AFTER TEMPORARY CORONARY ARTERY OCCLUSION. , 1963, The American surgeon.

[19]  矢吹 清一.  Time studies of acute,reversible,coronary occlusions in dogs. , 1961 .

[20]  C. Park,et al.  Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated, perfused heart of normal rats. , 1961, The Journal of biological chemistry.

[21]  W. J. Waddell,et al.  Calculation of intracellular pH from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO); application to skeletal muscle of the dog. , 1959, The Journal of clinical investigation.

[22]  J. Imbriglia,et al.  Time studies of acute, reversible, coronary occlusions in dogs. , 1959, The Journal of thoracic and cardiovascular surgery.

[23]  P. J. Randle,et al.  Regulation of glucose uptake by muscle. 3. The effects of insulin, anoxia, salicylate and 2:4-dinitrophenol on membrane transport and intracellular phosphorylation of glucose in the isolated rat heart. , 1959, The Biochemical journal.

[24]  L. Becker,et al.  Mapping of left ventricular blood flow with radioactive microspheres in experimental coronary artery occlusion. , 1973, Cardiovascular research.

[25]  C. Wiggers,et al.  THE EFFECT OF CORONARY OCCLUSION ON MYOCARDIAL CONTRACTION , 1935 .

[26]  D. Griggs,et al.  Effect of coronary constriction on myocardial distribution of iodoantipyrine-131-I. , 1968, The American journal of physiology.

[27]  M. Losada,et al.  Pentaerythritoltetranitrate and dipyridamole on cardiac nutritive flow and blood content. , 1971, The American journal of physiology.

[28]  R. Jennings,et al.  Structural Changes in Myocardium During Acute Ischemia , 1974, Circulation research.

[29]  M. Strohm,et al.  Extracellular acid-base changes in the dog myocardium during hypoxia and local ischemia, measured by means of glass micro-electrodes. , 1971, Cardiology.

[30]  H. Conn,et al.  Rate of Change in Myocardial Glycogen and Lactic Acid Following Arrest of Coronary Circulation , 1959, Circulation research.

[31]  M. Rovetto,et al.  Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat Hearts , 1973, Circulation research.

[32]  M. Rovetto,et al.  Effects of ischemia on function and metabolism of the isolated working rat heart. , 1973, The American journal of physiology.

[33]  J. Dobson,et al.  Mechanisms of Activation of Cardiac Glycogen Phosphorylase in Ischemia and Anoxia , 1973, Circulation research.

[34]  E. Sonnenblick,et al.  Effects of Hypoxia and Ischemia on Myocardial Contraction , 1971 .

[35]  R. H. Bowman,et al.  Effects of ventricular pressure development and palmitate on glucose transport. , 1969, The American journal of physiology.

[36]  E. J. Battersby,et al.  Effect of pressure development on oxygen consumption by isolated rat heart. , 1967, The American journal of physiology.

[37]  E. Krause,et al.  Endogenous Catecholamine Mobilization and the Shift to Anaerobic Energy Production in the Acutely Ischemic Myocardium , 1967 .

[38]  E. Linder.  Measurements of normal and collateral coronary blood flow by close-arterial and intramyocardial injection of krypton 85 and xenon 133. , 1966, Acta physiologica Scandinavica. Supplementum.