Changes in substrate metabolism in isolated mouse hearts following ischemia-reperfusion.
Several genetic and transgenic mouse models are currently being used for studying the regulation of myocardial contractility under normal conditions and in disease states. Little information has been provided, however, about myocardial energy metabolism in mouse hearts. We measured glycolysis, glucose oxidation and palmitate oxidation (using 3H-glucose, 14C-glucose and 3H-palmitate) in isolated working mouse hearts during normoxic conditions (control group) and following a 15 min global no-flow ischemic period (reperfusion group). Fifty min following reperfusion (10 min Langendorff perfusion + 40 min working heart perfusion) aortic flow, coronary flow, cardiac output, peak systolic pressure and heart rate were 44 +/- 4, 88 +/- 4, 57 +/- 4, 94 +/- 2 and 81 +/- 4% of pre-ischemic values). Rates of glycolysis and glucose oxidation in the reperfusion group (13.6 +/- 0.8 and 2.8 +/- 0.2 micromol/min/g dry wt) were not different from the control group (12.3 +/- 0.6 and 2.5 +/- 0.2 micromol/min/g dry wt). Palmitate oxidation, however, was markedly elevated in the reperfusion group as compared to the control group (576 +/- 37 vs. 357 +/- 21 nmol/min/g dry wt, p < 0.05). This change in myocardial substrate utilization was accompanied by a marked fall in cardiac efficiency measured as cardiac output/oxidative ATP production (136 +/- 10 vs. 54 +/- 5 ml/micromol ATP, p < 0.05, control and reperfusion group, respectively). We conclude that ischemia-reperfusion in isolated working mouse hearts is associated with a shift in myocardial substrate utilization in favour of fatty acids, in line with previous observations in rat.
Aasum
Ellen
E
Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø, Norway. ellenaa@fagmed.uit.no
Hafstad
Anne D
AD
Larsen
Terje S
TS
D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D051379:Mice; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism
D005227:Fatty Acids; D010168:Palmitates; D005947:Glucose