Effects of endogenous and exogenous lysophosphatidylcholine in isolated perfused rat hearts.
In isolated Langendorff perfused rat hearts, treatment with exogenous palmitoyl-lysophosphatidylcholine (P-LPC; 3-50 microM) under normoxic conditions, resulted in reduced heart rate (HR), coronary flow (CF) and contractile function. After 30 min Krebs perfusion, following P-LPC infusion, HR and CF remained reduced and contractile function continued to deteriorate. End diastolic pressure (EDP) and lactate dehydrogenase (LDH) release in LPC treated hearts were significantly increased from controls. Myocardial lysophosphatidylcholine (LPC) levels after 25 min global ischemia were significantly higher than controls (463 +/- 10 for control vs 550 +/- 15 nmol/g dry wt for ischemia). Following 30 min reperfusion an increase from control was still observed (475 +/- 11 for control vs. 594 +/- 17 for ischemia+reperfusion). Analysis of molecular species of LPC demonstrated that palmitoyl, oleoyl and stearoyl were increased after 25 min ischemia. After 30 min of reperfusion only palmitoyl and stearoyl were significantly increased. After 25 min treatment with 3 microM P-LPC and 30 min normoxic perfusion, myocardial LPC was three-fold higher than after 25 min ischemia. Treatment with 0.2 microM exogenous P-LPC resulted in myocardial tissue LPC levels (562 +/- 23) equivalent to those seen after 25 min ischemia (550 +/- 15). Compared to time matched controls hearts perfused with 0.2 microM P-LPC displayed no significant reductions in contractile function nor increase in LDH release. Thus, in isolated rat hearts, the increase in LPC seen after 25 min of global ischemia may not solely mediate the contractile dysfunction and LDH release observed.
Sargent
C A
CA
Bristol-Myers Squibb, Pharmaceutical Research Institute, Department of Pharmacology, Princeton, New Jersey 08543.
Vesterqvist
O
O
Ogletree
M L
ML
Grover
G J
GJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D008244:Lysophosphatidylcholines; C006065:We 201; D007770:L-Lactate Dehydrogenase