Biochemical and functional effects of nucleoside transport inhibition in the isolated cat heart.
With increasing periods of normothermic ischemia, increasing amounts of mainly inosine and hypoxanthine are released in reperfusates of isolated working cat hearts. Nucleoside transport inhibition (soluflazine; 1 x 10(-7) M) markedly reduces the total release, but increases the release of adenosine. Tissue levels of adenine nucleotides are reduced by 50% after 32 min of ischemia with an almost equivalent, parallel, rise in inosine and hypoxanthine. Subsequent reperfusion leads to a complete removal of the catabolites and a restoration of the energy charge, but not to any recovery of the sum of nucleotides. Nucleoside transport inhibition has no effect on the changes in the nucleotides, but induces a marked accumulation of adenosine during ischemia and prevents the rapid escape of the nucleosides--not of hypoxanthine--upon reperfusion. Cardiac function markedly deteriorates after 20 and 32 min of ischemia. Transport inhibition completely prevents the decrease in cardiac output and pressure-rate product without any effect on normoxic performance. It is suggested that the prolonged presence of adenosine and of inosine may exert a protective effect.
Department of Biochemistry, Janssen Research Foundation, Beerse, Belgium.
H
H
Van Belle
F
F
Goossens
J
J
Wynants
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002302:Cardiac Output; D002415:Cats; D003326:Coronary Circulation; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009705:Nucleosides / Q000378:metabolism*; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*
D000227:Adenine Nucleotides; D007042:Hypoxanthines; D009705:Nucleosides; D010710:Phosphates; D010879:Piperazines; D010725:Phosphocreatine; C054695:soluflazine; D019271:Hypoxanthine; D007288:Inosine; D000241:Adenosine