Changes in contractile function and endogenous fuel supply in rat heart upon perfusion with substrate-free medium.
Isolated rat hearts were perfused with aerobic substrate-free medium for different intervals during which changes in functional and metabolic events were examined. The contractile force was maintained for 30 min but thereafter declined toward zero over a period of 90 min. Before the onset of contractile failure, glycogen decreased by 60% of the control value, various intermediates of glycolytic flux, hexosephosphates, and triosephosphates, except dihydroxyacetone phosphate, reached their lowest level, and hydration of the myocardium became maximal. Furthermore, the phosphate potential, creatine phosphate (CrP), ATP, and oxygen consumption decreased by 60%, 45%, 10%, and 18%, respectively, before the onset of contractile failure. A progressive decrease in citrate, isocitrate, alpha-ketoglutarate, and malate was observed during a 2-hr perfusion period, but a slight increase in the levels of oxaloacetate and acetyl-CoA was apparent at 30 and 60 min, respectively. The early phase of contractile failure (30-60 min) was associated with an increase in the free fatty acid (FFA) and AMP levels, whereas the late phase (90-120 min) was characterized by an increase in resting tension and a decrease in oxygen consumption. The complete failure of the heart to generate contractile force at 120 min of perfusion occurred when about 40% of the glycogen and ATP contents and about 25% of the creatine phosphate and triglyceride contents were still present. Therefore, contractile failure of the hearts perfused with substrate-free medium may be caused by an insufficiency of the mechanisms responsible for the mobilization of endogenous glycogen and triglycerides as well as for the generation and utilization of ATP.
D000105:Acetyl Coenzyme A / Q000032:analysis; D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D006003:Glycogen / Q000032:analysis / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000032:analysis; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats
D005230:Fatty Acids, Nonesterified; D009943:Organophosphorus Compounds; D000105:Acetyl Coenzyme A; D006003:Glycogen