title: Protective effects of L-659,989, a platelet-activating factor receptor antagonist, in myocardial ischemia and reperfusion in rats.
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.
authors.affiliation: Institute of Pharmacology, School of Medicine, University of Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ioculano
authors.forename: F
authors.initials: F
authors.lastname: Squadrito
authors.forename: D
authors.initials: D
authors.lastname: Altavilla
authors.forename: P
authors.initials: P
authors.lastname: Canale
authors.forename: G M
authors.initials: GM
authors.lastname: Campo
authors.forename: F
authors.initials: F
authors.lastname: Bussolino
authors.forename: A
authors.initials: A
authors.lastname: Sardella
authors.forename: G
authors.initials: G
authors.lastname: Urna
authors.forename: A P
authors.initials: AP
authors.lastname: Caputi
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D005663:Furans / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015996:Survival Rate
chemical_list: D005663:Furans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C054893:L 659989; D009195:Peroxidase; D003402:Creatine Kinase