Stimulation of carbohydrate metabolism reduces hypothermia-induced calcium load in fatty acid-perfused rat hearts.
In the present study we examined the impact of glycolysis and glucose oxidation on myocardial calcium control and mechanical function of fatty acid-perfused rat hearts subjected to hypothermia rewarming. One group (control) was given glucose (11.1 mM) and palmitate (1.2 mM) as energy substrates. In a second group glycolysis was inhibited by iodoacetate (IAA, 100 microM) and replacement of glucose with pyruvate (5 mM), whereas in the third group glucose oxidation was stimulated by administration of dichloroacetate (DCA, 1 mM) and insulin (500 microU/ml). All groups showed a rise in myocardial calcium ([Ca]total in response to hypothermia (10 degrees C). However, [Ca]total was significantly lower both in IAA- and DCA-treated hearts, as compared to controls (2.20 +/- 0.22 and 2.94 +/- 0.20 v 3.83 +/- 0.29 nmol/mg dry wt., P < 0.025). The reduced calcium load in the treated hearts was correlated with higher levels of high energy phosphates. Following rewarming control and DCA-treated hearts still showed elevated [Ca]total, whereas IAA-treated hearts [Ca]total was not different from the pre-hypothermic value. All groups showed a reduction in cardiac output following rewarming. Furthermore, the control group, in contrast to both IAA- and DCA-treated hearts, showed a significant reduction in systolic pressure. These results show that hypothermia-induced calcium uptake in glucose and fatty acid-perfused rat hearts was reduced by two different metabolic approaches: (1) inhibition of glycolysis by IAA while simultaneously by-passing the glycolytic pathway by exogenous pyruvate: and (2) stimulation of glucose oxidation by DCA. Thus, glycolytic ATP is not an essential regulator of sarcolemmal calcium transport under the present experimental conditions. Instead, we suggest that a change in oxidative substrate utilization in favour of carbohydrates may improve myocardial calcium homeostasis during hypothermia and rewarming.
Aasum
E
E
Department of Medical Physiology, Institute of Medical Biology, University of Tromso, Norway.
Steigen
T K
TK
Larsen
T S
TS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D050260:Carbohydrate Metabolism; D002302:Cardiac Output; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007035:Hypothermia / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010477:Perfusion / Q000379:methods; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose; D002118:Calcium