Glycolysis and glucose oxidation during reperfusion of ischemic hearts from diabetic rats.
Stimulation of glucose oxidation by dichloroacetate (DCA) treatment is beneficial during recovery of ischemic hearts from non-diabetic rats. We therefore determined whether DCA treatment of diabetic rat hearts (in which glucose use is extremely low), increases recovery of function of hearts reperfused following ischemia. Isolated working hearts from 6 week streptozotocin-diabetic rats were perfused with 11 mM [2-3H/U-14C]glucose, 1.2 mM palmitate, 20 microU/ml insulin, and subjected to 30 min of no flow ischemia followed by 60 min reperfusion. Heart function (expressed as the product of heart rate and peak systolic pressure), prior to ischemia, was depressed in diabetic hearts compared to controls (HR x PSP x 10(-3) was 18.2 +/- 1 and 24.3 +/- 1 beats/mm Hg/min in diabetic and control hearts respectively) but recovered to pre-ischemic levels following ischemia, whereas recovery of control hearts was significantly decreased (17.8 +/- 1 and 11.9 +/- 3 beats/mm Hg/min in diabetic and control hearts respectively). This enhanced recovery of diabetic rat hearts occurred even though glucose oxidation during reperfusion was significantly reduced as compared to controls (39 +/- 6 and 208 +/- 42 nmol/min/g dry wt, in diabetic and control hearts respectively). Glycolytic rates (3H2O production) during reperfusion were similar in diabetic and control hearts (1623 +/- 359 and 2071 +/- 288 nmol/min/g dry wt, respectively). If DCA (1 mM) was added at reperfusion, hearts from control animals exhibited a significant improvement in function (HR x PSP x 10(-3) recovered to 20 +/- 4 beats/mm Hg/min) that was accompanied by a 4-fold increase in glucose oxidation (from 208 +/- 42 to 753 +/- 111 nmol/min/g dry wt). DCA was without effect on functional recovery of diabetic rat hearts during reperfusion but did significantly increase glucose oxidation from 39 +/- 6 to 179 +/- 44 nmol/min/g dry wt). These data suggest that, unlike control hearts, low glucose oxidation rates are not an important factor in reperfusion recovery of previously ischemic diabetic rat hearts.
Gamble
J
J
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Lopaschuk
G D
GD
D000818:Animals; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003999:Dichloroacetic Acid / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D006339:Heart Rate; D066298:In Vitro Techniques; D008297:Male; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D003999:Dichloroacetic Acid; D005947:Glucose