Protection of the reperfused ischemic isolated rat heart by phosphatidylcholine.
We examined phosphatidylcholine (PC) effects on the isolated rat heart subjected to low- or zero-flow ischemia followed by reperfusion. Untreated hearts subjected to 30 min of low-flow ischemia recovered 15% contractility following reperfusion compared to time-control hearts. Phosphatidylcholine (0.005%) addition either 10 or 20 min before ischemia significantly enhanced recovery to approximately 61% and reduced the incidence of arrhythmias during ischemia and reperfusion. Contracture during ischemia and reperfusion was significantly reduced when PC was added 20 min before ischemia. Phosphatidylcholine was ineffective when administered at the time of reperfusion except for a moderate reduction in arrhythmia development. Phosphatidylcholine also produced a salutary effect when added 20 min prior to zero-flow ischemia. Subsarcolemmal mitochondria (SLM) and, to a much lesser degree, interfibrillar mitochondria (IFM) of untreated hearts subjected to low-flow ischemia and reperfusion exhibited depressed oxidative phosphorylation which was prevented by PC. Both mitochondrial populations exhibited a marked depression in ADP/ATP translocase activity; however, this was generally unaffected by PC. Subsarcolemmal mitochondria but not IFM of zero-flow ischemic reperfused hearts also exhibited significantly depressed oxidative phosphorylation, which was unaffected by PC. Zero-flow ischemia produced a rapid and total cessation of contractility. Both populations exhibited a substantial PC-insensitive reduction in translocase activity. Our results demonstrate, for the first time, a protection by PC on the reperfused ischemic heart. The PC-induced protection following low-flow but not zero-flow ischemia is associated with improved SLM oxidative phosphorylation suggesting dissimilar contribution of mitochondria to reperfusion-associated myocardial injury.
Duan
J M
JM
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Karmazyn
M
M
D000818:Animals; D005971:Glutamates / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008293:Malates / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005971:Glutamates; D008293:Malates; D010713:Phosphatidylcholines; D000226:Mitochondrial ADP, ATP Translocases