Protective effects of l-659,989, a platelet-activating factor receptor antagonist, in myocardial ischemia and reperfusion in rats

Mariapatrizia Ioculano, Francesco Squadrito, Domenica Altavilla, Patrizia Canale, Giuseppe M. Campo, Federico Bussolino, Aurora Sardella, Giuseppe Urna, Achille P. Caputi

Research output: Contribution to journalArticle

Abstract

The cardioprotective effects of L-659,989, a specific platelet-activating factor (PAF) receptor antagonist, were investigated in an ischemia/reperfusion model in rats. Pentobarbital-anesthetized rats were subjected to left main coronary artery occlusion (1 h) followed by reperfusion (1 h) (MI/R); Sham-operated rats were used as controls (Sham MI/R). Rats receiving vehicle showed reduced survival rate (60%), marked myocardial injury (necrotic area/total area = 54.5 ± 6%; necrotic area/area at risk 76.6 ± 6.7%), high serum creatine phosphokinase (CPK) activity (150 ± 10 U/ml), and increased myocardial myeloperoxidase (MPO) activity in the area at risk (AR, 6.2 ± 0.5 U x 10-3/g protein) and in the necrotic area (6.6 ± 0.7 U x 10-3/g protein). PAF plasma levels increased significantly during reperfusion and peaked at 15 min of reperfusion. Administration of L-659,989 enhanced survival rate (80%), reduced myocardial damage (necrotic area/total area 25.6 ± 3.5%; necrotic area/AR 34.6 ± 5.4%), attenuated the increase in serum CPK (50 ± 6 U/ml) and decreased MPO activity both in the AR (2.8 ± 0.3 U x 10-3/g tissue) and in the necrotic area (2.3 ± 0.5 U x 10-3/g tissue). Our results suggest that PAF-inducing adhesion and activation of polymorphonuclear leukocytes (PMN) plays a significant role in the injury associated with ischemia/reperfusion.

Original languageEnglish
Pages (from-to)7-12
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume23
Issue number1
Publication statusPublished - 1994

Keywords

  • L-659,989
  • Myocardial ischemia/reperfusion
  • Platelet-activating factor receptor antagonist

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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    Ioculano, M., Squadrito, F., Altavilla, D., Canale, P., Campo, G. M., Bussolino, F., Sardella, A., Urna, G., & Caputi, A. P. (1994). Protective effects of l-659,989, a platelet-activating factor receptor antagonist, in myocardial ischemia and reperfusion in rats. Journal of Cardiovascular Pharmacology, 23(1), 7-12.