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Pyruvate attenuation of hypoxia damage in isolated working guinea-pig heart.

Abstract：

:Function and various parameters of myocardial substrate and energy metabolism were measured in preload-controlled isolated working guinea-pig hearts perfused with normoxic (95% O2) and hypoxic (30 to 45% O2) Krebs-Henseleit buffers ([Ca2+] = 1.25 mM). Energy-yielding substrates were glucose, pyruvate, lactate, and fatty acids (acetate, octanoate). Hypoxia typically produced an increase in coronary flow but a fall in cardiac oxygen uptake (MVO2); left ventricular pressure and work parameters as well as myocardial high energy phosphate levels were decreased while the releases of adenosine plus inosine (V (Ado + Ino)) and lactate were increased. Extra pyruvate (1 to 5 mM) as compared to physiologic concentrations of pyruvate (0.2 mM) produced a relative stabilization of left ventricular pressure and work parameters combined with an attenuation of V (Ado + Ino) provided 5 to 10 mM glucose was the cosubstrate. Coinfusion of 2-deoxyglucose, a nondegradable hexose, in presence of excess pyruvate as sole substrate was without effects on residual ventricular pump function. When 1 mM lactate plus 5 mM glucose were the substrates, hypoxic heart function was also depressed, V (Ado + Ino) was relatively increased, and post-hypoxic recovery of pressure parameters was impaired. Similarly, the fatty acid substrates tested seemed to adversely affect cardiac performance during hypoxia. Extra pyruvate in presence of glucose induced a fall in hypoxic myocardial lactate and alpha-glycerophosphate contents while cellular citrate reached millimolar levels. Obviously, utilizable amounts of glucose were required for pyruvate stabilization of the high flow hypoxic heart. The beneficial effects of pyruvate appeared to depend on a functioning glycolysis; other effects seemed to include redox-related changes in energy state and/or purine nucleoside metabolism as well as a possible citrate buffering of intracellular Ca2+ load.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Bünger R,Swindall B,Brodie D,Zdunek D,Stiegler H,Walter G

doi

10.1016/s0022-2828(86)80905-1

subject

Has Abstract

pub_date

1986-04-01 00:00:00

pages

423-38

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(86)80905-1

journal_volume

pub_type

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Pyruvate attenuation of hypoxia damage in isolated working guinea-pig heart.