The present study was designed to evaluate the effects of
POCA, a
carnitine palmitoyltransferase I (
CPT I) inhibitor, and
pyruvate, a substrate inhibiting
fatty acid (FA) oxidation, on post-ischemic cardiac FA accumulation on the one hand, and hemodynamic recovery and loss of cellular integrity on the other. To this end isolated, working rat hearts, receiving
glucose (11 mM) as substrate, were subjected to 45 min of no-flow
ischemia and 30 min of reperfusion. Hearts were perfused with or without
POCA (10 microM) and/or
pyruvate (5 mM). In the control group the FA content increased significantly during
ischemia and remained elevated during reperfusion. Administration of
POCA did not affect functional recovery and LDH release significantly, but resulted in about two-fold increased FA levels upon reperfusion as compared to
glucose-perfused hearts.
Pyruvate markedly improved functional recovery. Addition of this substrate did not affect
lactate dehydrogenase (LDH) release, but enhanced FA accumulation during reperfusion. The combined administration of
pyruvate and
POCA nullified the positive effect of
pyruvate on hemodynamic recovery, aggravated LDH release, and further enhanced the accumulation of FAs. The
adenine nucleotide content of reperfused hearts was comparable for all groups investigated. In conclusion, during transient
ischemia POCA and
pyruvate markedly increased cardiac FA accumulation through inhibition of the oxidation of FAs released from endogenous
lipid pools. No clear relation was found between the FA content of reperfused hearts and post-ischemic functional recovery.