Substrate competition in postischemic myocardium. Effect of substrate availability during reperfusion on metabolic and contractile recovery in isolated rat hearts.
Normal myocardium can derive energy for contraction and relaxation from oxidative metabolism of a variety of substrates. This investigation examined the influence of substrate availability early during reperfusion on the substrate pattern of oxidative metabolism and recovery of contractile function. For this purpose, isovolumically beating isolated rat hearts, perfused retrogradely with erythrocyte-supplemented buffer containing 0.4 mmol/L palmitate and 11 mmol/L glucose, were subjected to 40 minutes of no-flow ischemia. Hearts were reperfused with medium containing selected concentrations of palmitate and glucose. The substrate pattern for oxidative metabolism was determined on the basis of myocardial release of 14CO2 after equilibration of the hearts during the initial 15 minutes of reperfusion with either [1-14C]palmitate or [U-14C]glucose. In continuously perfused control hearts, glucose oxidation was largely inhibited by palmitate. During postischemic reperfusion, oxidation of glucose was increased by 59% (P < .05) and 467% (P <.01) in hearts reperfused after the ischemic period with 11 mmol/L glucose plus 0.4 or 1.2 mmol/L palmitate, respectively. Oxidation of palmitate was concomitantly reduced during reperfusion at low (0.4 mmol/L) but not at high (1.2 mmol/L) palmitate concentration. Compared with hearts reperfused with medium containing 0.4 mmol/L palmitate as sole substrate, hearts reperfused with medium containing 11 mmol/L glucose with 0.4 mmol/L palmitate exhibited lower left ventricular diastolic pressure (69 +/- 5 versus 90 +/- 3 mm Hg [mean +/- SEM], P < .05), less release of creatine kinase (31 +/- 5 versus 59 +/- 7 U/g wet wt, P < .05), and better recovery of left ventricular pressure development (26 +/- 9 versus 6 +/- 4 mm Hg, P < .05). Omission of palmitate or increasing the palmitate concentration to 1.2 mmol/L did not significantly alter postischemic myocardial contracture and enzyme release. The findings support the view that glucose oxidation early during reperfusion may be crucial for functional recovery. The results further indicate that interaction of substrates of oxidative metabolism is altered in severely injured postischemic myocardium. Inhibition of glucose oxidation by fatty acids was partially reversed during reperfusion.
Tamm
C
C
Cardiology Center, University Hospital, Geneva, Switzerland.
Benzi
R
R
Papageorgiou
I
I
Tardy
I
I
Lerch
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats
D005227:Fatty Acids; D007773:Lactates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D005947:Glucose; D010100:Oxygen