[Attenuation of irreversible rat heart injury by reperfusion with metabolic protectors].
The aim of this study was to evaluate the effects of intravenous infusion of potassium-magnesium aspartate (K-Mg-Asp), a glucose-insulin-potassium cocktail (GIK), a combination of glucose, insulin and potassium aspartate (GIKAsp), and insulin (I) alone during reperfusion after myocardial regional ischemia on metabolism of the risk area (AR) and cardiomyocyte membrane damage in rats in vivo. Acute myocardial infarction (MI) was induced by 40-min occlusion of the anterior descending coronary artery followed by 60-min reperfusion. At the onset of reperfusion, K-Mg-Asp, GIK, GIKAsp, I or the physiological solution (control) was infused into the jugular vein at a rate of 1 ml/kg/h. After reperfusion, MI size was estimated by myocardial staining with 2,3,5-triphenyltetrazolium chloride. In separate series transmural biopsies from the AR were taken for metabolite analysis. MI size in all experimental groups was less than that in the control and reduced in the following rank: K-Mg-Asp > GIKAsp > I > GIK. By the end of reperfusion with metabolic protectors, ATP and phosphocreatine levels in the AR were 2-2,5 times higher that in the control (56.3 +/- 3.4 and 81.8 +/- 7.9% of the initial values, respectively). The losses of aspartate and glutamate pool and lactate and glucose accumulation in the AR were significantly lower in the experimental groups than in control. At the end of the reperfusion, the total creatine content in the AR decreased to 32.3 +/- 2.3% of the initial value in control, but restored to 78.0 +/- 5.7; 76.7 +/- 5.5 and 62.4 +/- 5.6% under effects of GIK, I and K-Mg-Asp, respectively. The recovery of the majority indices of aerobic metabolism and cell membrane integrity was maximal in the GIK and I groups and insignificantly lower after reperfusion with K-Mg-Asp. Therefore the metabolic efficacy of the protectors on reperfusion corresponded to MI size limitation. The results suggest that myocardial reperfusion with GIK, I and K-Mg-Asp is a promising adjunctive therapy in patients with acute MI.
Pisarenko
O I
OI
Serebriakova
L I
LI
Tsikitishvili
O V
OV
Studneva
I M
IM
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D005947:Glucose / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D011188:Potassium / Q000627:therapeutic use; D011195:Potassium Magnesium Aspartate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D004338:Drug Combinations; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; C024653:Asparkam; D011195:Potassium Magnesium Aspartate; D005947:Glucose; D011188:Potassium