Rate of glycolysis during ischemia determines extent of ischemic injury and functional recovery after reperfusion.
The efficacy of increasing glycolysis during ischemia for enhancing the salutary effects of reperfusion was evaluated in isolated perfused rabbit hearts subjected to low-flow ischemia followed by reperfusion. Control hearts were perfused with buffer containing 0.4 mM palmitate, 5 mM glucose, and 70 mU/l insulin. Additional groups of hearts were perfused with double glucose/insulin and 1 mM dichloroacetate or were subjected to substrate priming to increase preischemic glycogen content. Ischemic contracture was completely prevented in hearts perfused with high glucose/insulin and was delayed markedly by either dichloroacetate or enhanced preischemic glycogen [45 +/- 14 and 31 +/- 20 min, respectively; P < 0.01 each vs. control (11 +/- 10 min)] and inversely related to the rate of lactate production. With reperfusion, recovery of developed pressure was 56 +/- 23% of baseline in control hearts, 90 +/- 8% in hearts receiving high glucose/insulin, 92 +/- 5% in hearts receiving dichloroacetate, and 79 +/- 19% in hearts with increased glycogen (P < 0.05 each vs. control hearts). Creatine kinase release was reduced by > 55% in treated hearts. Thus enhancement of glycolysis by diverse mechanisms during ischemia decreased ischemic damage and improved the recovery of contractile function with reperfusion.
Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri 63110.
J L
JL
Vanoverschelde
M F
MF
Janier
J E
JE
Bakke
D R
DR
Marshall
S R
SR
Bergmann
D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure; D001834:Body Water / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D006339:Heart Rate; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D011817:Rabbits; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D016277:Ventricular Function, Left
D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D014280:Triglycerides; D006003:Glycogen; D003999:Dichloroacetic Acid; D005947:Glucose