Effects of acylcarnitine-transferase inhibitors on adenine nucleotide metabolism and ischemic tissue injury in isolated perfused rat heart.
The ability of irreversible acylcarnitine-transferase inhibitors, sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) and 2-tetradecyl-glycidic acid (TDGA), to reduce myocardial ischemic injury was studied in Langendorff-perfused hearts exposed to ischemia (zero mmHg) followed by aerobic reperfusion (60 mmHg). Rat hearts were pretreated with either POCA (15 mg/kg) or TDGA (5 mg/kg) s.c. 120 min before the perfusion. Treated hearts showed a decreased release of creatine kinase and lactate on reperfusion after 30 min ischemia. POCA-treated hearts showed significantly higher ATP concentrations than control hearts on reperfusion. POCA also improved the maximum recovery of the pressure-rate product but with a significant delay. During the ischemic period, though, POCA decreased the ATP concentration at a rate three times that of controls during the first 10 min. No further reductions were observed for up to 30 min of ischemia. TDGA also showed a reduction of ATP. Thus, the observation that POCA stimulated ATP synthesis and reduced creatine kinase release on reperfusion after ischemia suggests that this agent provides some protection to the ischemic myocardium. However, during ischemia, it is likely that the depletion of ATP concentration induced by POCA resulted in delayed recovery of mechanical function on reperfusion.
Shikama
H
H
Department of Biochemistry, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Noshiro
O
O
Ohta
A
A
Ohata
I
I
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D003327:Coronary Disease / Q000473:pathology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion; D013997:Time Factors
D000227:Adenine Nucleotides; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005227:Fatty Acids; D010168:Palmitates; C033891:ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate; D000217:Acyltransferases; C021756:2-tetradecylglycidic acid