title: Lysophosphatidylcholine-induced myocardial damage is inhibited by pretreatment with poloxamer 188 in isolated rat heart.
abstract: 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.
authors.affiliation: Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan. makinow@med.juntendo.ac.jp
authors.forename: Makino
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takao
authors.initials: T
authors.lastname: Okada
mesh_terms: 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
chemical_list: D008244:Lysophosphatidylcholines; D013501:Surface-Active Agents; D020442:Poloxamer