Lysophosphatidylcholine-induced myocardial damage is inhibited by pretreatment with poloxamer 188 in isolated rat heart.
Lysophosphatidylcholine (LPC) accumulates in myocardial tissues and coronary sinus during ischemia, and plays important role in the development of ischemia-reperfusion injury and ischemic ventricular arrhythmia. The aim of this study was to examine whether pretreatment of poloxamer 188 (P-188), a nonionic and non-toxic surfactant, can prevent the cardiac dysfunction induced by exogenous LPC perfusion in Langendorff perfused rat heart model. LPC (6 microM) significantly (p < 0.05) decreased heart rate (HR) and left ventricular developed pressure (LVDP) from 274.3 +/- 23.2 to 175.0 +/- 42.9/min and from 115.9 +/- 11.3 to 26.7 +/- 7.1 mmHg, respectively. The LPC-induced reduction of HR and LVDP did not recover by washout of LPC. Pretreatment with P-188 (1 mM for 30 min) inhibited completely the LPC-induced decreases of HR and LVDP. The pretreatment with P-188 also prevented the LPC-induced increases of left ventricular end-diastolic pressure (LVEDP) and GOT release, significantly (p < 0.05). The coronary perfusion pressure (CPP) rose (p < 0.01) by the LPC perfusion from 71.9 +/- 5.3 to 121.9 +/- 13.0 mmHg, significantly, but pretreatment of P-188 did not affect the LPC-induced vasoconstriction. Our results suggest that exogenous LPC causes irreversible cardiac injury by the sarcolemmal membrane disruption followed by Ca overload, and this LPC-induced cardiac injury, probably, can be prevented by the pretreatment with poloxamer 188.
Watanabe
Makino
M
Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan. makinow@med.juntendo.ac.jp
Okada
Takao
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010477:Perfusion; D020442:Poloxamer / Q000494:pharmacology*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors; D017725:Ventricular Pressure
D008244:Lysophosphatidylcholines; D013501:Surface-Active Agents; D020442:Poloxamer