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.
|Number of pages||6|
|Journal||Journal of Cardiovascular Pharmacology|
|Publication status||Published - 1994|
- Myocardial ischemia/reperfusion
- Platelet-activating factor receptor antagonist
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine