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Effects of POCA on metabolism and function in the ischemic rat heart |
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| Authors: | D. J. Paulson J. J. Noonan K. M. Ward H. Stanley A. Sherratt Dr. A. L. Shug |
| Affiliation: | (1) Present address: Metabolic Research Laboratory, William S. Middleton Memorial Veterans Administration Hospital, 2500 Overlook Terrace, 53705 Madison, WI, (USA);(2) Department of Neurology, University of Wisconsin-Madison, 53706 Madison, WI, (USA);(3) Department of Physiology, Chicago College of Osteopathic Medicine, 60615 Chicago, IL;(4) Department of Pharmacological Sciences, University of Newcastle upon Tyne, NE1 7RU Newcastle upon Tyne, UK |
| Abstract: | Summary Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) inhibits carnitine palmityltransferase I and fatty acid oxidation. The effects of POCA on cardiac function and on tissue levels of carnitine and coenzyme A esters were studied in the isolated rat heart subjected to 90 minutes of ischemia with and without 15 minutes of reperfusion. The perfusion medium contained 1.2 mM palmitate and 5.5 mM glucose plus or minus 0.5 mM POCA. This compound prevented accumulation of long-chain acylcarnitine and coenzyme A esters during ischemia and significantly improved the recovery of cardiac output after ischemia and reperfusion. Short-chain acylcarnitine levels were increased during ischemia by POCA. No effects were noted on tissue ATP and lactate levels. POCA may protect the ischemic heart by preventing accumulation of these toxic metabolites and by stimulating glucose utilization during ischemia.Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylateThis work was supported by the Veterans Administration and NIH HL 17736 |
| Keywords: | POCA fatty acid oxidation carnitine coenzyme A ischemia |
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