Open AccessS1P1-Selective Agonist SEW2871 Exacerbates Reperfusion Arrhythmias
Author(s) -
Yayoi Tsukada,
Marta Sanna,
Hugh Rosen,
Roberta A. Gottlieb
Publication year - 2007
Publication title -
journal of cardiovascular pharmacology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/fjc.0b013e318157a5fe
Subject(s) - agonist , cardiology , ventricular fibrillation , medicine , ischemia , ventricular tachycardia , reperfusion injury , sphingosine 1 phosphate receptor , fibrillation , anesthesia , receptor , sphingosine 1 phosphate , sphingosine , atrial fibrillation
Sphingosine-1-phosphate (S1P) has been considered to play an important role in ischemia/reperfusion (I/R) injury. We used SEW2871 (SEW), a novel receptor-selective agonist for S1P1, to elucidate the role of S1P1 in myocardial I/R. Isolated perfused rat hearts exposed to S1P (1 and 10 mM) or SEW (1 and 0.1 mM) were subjected to 30 minutes of global no-flow ischemia and 2 hours of reperfusion. S1P at 1 and 10 mM significantly reduced infarct size and CK release compared with vehicle-control. The effect of 0.1 microM SEW on infarct size was modest. After I/R, S1P at both doses and SEW at 0.1 microM improved developed pressure (LVDP). SEW at 1 mM significantly prolonged the duration of ventricular tachycardia and ventricular fibrillation, leading to irreversible reperfusion tachyarrhythmias in 60% of the hearts. This is the first demonstration of the critical role of the S1P1 receptor in I/R injury.