Correlation between [5-3H]glucose and [U-14C]deoxyglucose as markers of glycolysis in reperfused myocardium.
Studies were conducted in extracorporeally perfused, intact, working pig hearts to determine whether, in heart muscle, trace-labeled deoxyglucose serves as an accurate marker of glycolytic flux in reperfusion after exposures to mild to moderate regional ischemia. In the main study, two groups of hearts were compared, as distinguished by levels of glucose in the whole-blood perfusate (euglycemic hearts [group I], blood glucose of 7.4 +/- 0.2 mumol/ml, n = 7; hyperglycemic hearts [group II], blood glucose of 12.9 +/- 0.5 mumol/ml, n = 8). Both groups were subjected to a 60% reduction in anterior descending coronary flow for 30 minutes followed by reperfusion for 40 minutes. Modest and comparable regional mechanical stunning during reflow was noted in both groups. Glucose utilization, as estimated from the release of 3H2O from the steady-state infusion of [5-3H]glucose during aerobic perfusion, was modest but during reperfusion was noted to increase significantly above aerobic values in each of the two groups, with a doubling of rates in group II hearts compared with group I hearts (p less than 0.041 or p less than 0.090). Net lactate extraction was comparable in reflow in both groups, suggesting in this specific instance a preferential enhancement of glucose oxidation in hyperglycemic group II hearts. Shifts in accumulation of tissue radioactivity of [U-14C]2-deoxyglucose in reperfused myocardium were not able to track these trends. The variability of 14C-labeled radioactivity among animals was marked and essentially masked any ability to discern trends in glycolysis as described by tritiated glucose between the aerobic and reperfusion intervals. When the data were arrayed by linear regression analysis, the slopes derived from 14C-labeled deoxyglucose were either discordant or insensitive to those described by 3H-labeled glucose. Tissue glycogen levels were slow to recover in early reflow and at end reperfusion were still significantly depressed from aerobic levels. The present data indicate that coronary reperfusion and hyperglycemia have influence in determining glycolytic flux in myocardium. Labeled deoxyglucose, considered solely as a marker of exogenous glucose utilization, appears to be an insensitive agent in describing these events at conditions of relatively low glucose flux.
Liedtke
A J
AJ
Cardiology Section, University of Wisconsin Hospital and Clinics, Madison 53792.
Renstrom
B
B
Nellis
S H
SH
D000818:Animals; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000032:analysis; D006019:Glycolysis; D006943:Hyperglycemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D014316:Tritium
D002250:Carbon Radioisotopes; D014316:Tritium; D006003:Glycogen; D003847:Deoxyglucose; D005947:Glucose