Lysophosphatidylcholine-induced myocardial damage is inhibited by pretreatment with poloxamer 188 in isolated rat heart

Mol Cell Biochem. 2003 Jun;248(1-2):209-15. doi: 10.1023/a:1024165125139.

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.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Heart / drug effects
  • Ischemic Preconditioning, Myocardial*
  • Lysophosphatidylcholines / pharmacology*
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Perfusion
  • Poloxamer / pharmacology*
  • Pressure
  • Rats
  • Rats, Sprague-Dawley
  • Surface-Active Agents / pharmacology*
  • Time Factors
  • Ventricular Pressure

Substances

  • Lysophosphatidylcholines
  • Surface-Active Agents
  • Poloxamer