Physiological insulin concentrations protect against ischemia-induced loss of cardiac function in rats.
This study determined whether insulin at pre- (fasting) and post-prandial concentrations increases coronary blood flow and improves cardiac function after acute ischemia during a situation of myocardial stunning. The experiments were performed using an isolated, erythrocyte perfused, working rat heart model. To the perfusate we added erythrocytes and 1.5% bovine serum albumin to improve clinical relevance. The following protocol was used: 8 min baseline performance assessment, 10 min pre-ischemic treatment, 12 min global ischemia, 20 min post-ischemic treatment and 8 min recovery assessment. Vehicle, 10 mIU l(-1) and 100 mIU l(-1) human insulin were tested (all n=6). No significant vasodilator response to insulin was observed either pre- or post-ischemically. After the 12-min ischemic insult, cardiac function returned dose-dependently to pre-ischemic values (function loss with 100 mIU l(-1) insulin: -0.2+/-0.4% vs. vehicle: 10.7+/-0.8%). This study clearly shows that in our clinically relevant model of moderate ischemia (stunning), insulin is highly cardioprotective at physiological concentrations. This may be explained primarily by higher glucose uptake, improving the myocardial energetic state during ischemia. Therefore, insulin should be considered for use when the myocardium is at acute risk for ischemic incidents.
Legtenberg
Roger J
RJ
Department of Physiology, University Medical Center Nijmegen, NL-6500 HB Nijmegen, The Netherlands.
Houston
Ralph J F
RJ
Oeseburg
Berend
B
Smits
Paul
P
D000818:Animals; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000517:prevention & control*; D017682:Myocardial Stunning; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007328:Insulin