Different effects of thiopental in severe hypoxia, total ischemia, and low-flow ischemia in rat heart muscle.
The effect of thiopental (100 mg X 1(-1] during total ischemia, low-flow ischemia, and severe hypoxia with maintained flow was investigated in the isolated perfused rat heart. During total ischemia the rate of decline of tissue creatine phosphate and adenosine triphosphate was no different in thiopental-treated and untreated hearts. The development of ultrastructural damage during total ischemia, the release of creatine kinase on reperfusion, and the exacerbation of ultrastructural damage after reperfusion were unaffected by thiopental. When thiopental was added to the perfusate during hypoxia and during low-flow ischemia at a normal pH(7.4), creatine kinase release during reoxygenation and during reperfusion was significantly less (P less than 0.005 and P less than 0.05, respectively) than in the untreated groups. After low-flow ischemia at a low pH (6.5), creatine kinase release was no different in thiopental-treated and untreated hearts. Thus, thiopental afforded protection of the myocardium in hypoxia and low-flow ischemia at pH 7.4 but not in total ischemia and low-flow ischemia at pH 6.5. The data are consistent with the hypothesis that during total ischemia and low-flow ischemia at pH 6.5, acidosis favors the entry of thiopental into the cell, causing inhibition of mitochondrial function and reduction of ATP production. During hypoxic perfusion and low-flow ischemia at pH 7.4, when the decrease in pH is less, the cardiodepressant effect of thiopental may offset any deleterious effect of the drug on intracellular organelles such as mitochondria.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism* / Q000473:pathology; D003402:Creatine Kinase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013874:Thiopental / Q000494:pharmacology*
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D013874:Thiopental