Potentiation of the depressant effects of lysophosphatidylcholine on contractile properties of cultured cardiac myocytes by acidosis and superoxide radical.
Lysophosphatidylcholine (LPC) accumulates in the heart during myocardial ischemia. This amphiphile accelerates Ca++ flux in cardiac myocytes and may mediate ischemic cell injury. In the present study, we evaluated the effects of LPC on the contractility of cultured neonatal rat heart cells. We also investigated the interactions between LPC and other prominent features of the ischemic milieu, acidosis, and superoxide radical. A photo-optical technique was used to measure the maximum velocities of shortening and relaxation (dS/dt and dR/dt) of cultured cells superfused with 0.1 to 100 mumol/L LPC. LPC, at all concentrations, initially increased dS/dt. After 1 minute, however, dS/dt decreased in a concentration-dependent manner in cells superfused with greater than 20 mumol/L LPC. The effect of LPC on relaxation was also dependent on LPC concentration. dR/dt increased at less than 40 mumol/L LPC but decreased at greater than or equal to 60 mumol/L LPC. Acidosis markedly potentiated LPC-mediated depression in dS/dt and dR/dt. In contrast, superoxide dismutase entirely prevented LPC-mediated depression of contractility. We conclude that whereas brief exposure to LPC stimulates contractility, prolonged exposure to greater than 40 mumol/L LPC depresses dS/dt and dR/dt in cultured myocytes. The depressant effects of LPC on contractility are potentiated by acidosis and superoxide radical. We postulate that LPC accumulation in the myocardium contributes to ischemia-mediated contractile dysfunction.
Sedlis
S P
SP
Cardiology Department, New York Veterans Administration Medical Center, NY 10010.
Sequeira
J M
JM
Altszuler
H M
HM
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003327:Coronary Disease / Q000503:physiopathology; D003864:Depression, Chemical; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*
D005609:Free Radicals; D008244:Lysophosphatidylcholines; D013481:Superoxides; D013482:Superoxide Dismutase