Role of platelet-activating factor in polymorphonuclear neutrophil recruitment in reperfused ischemic rabbit heart.
This study investigated the role of platelet-activating factor in the recruitment of polymorphonuclear neutrophils (PMN) in a rabbit model of cardiac ischemia and reperfusion. The accumulation of PMN was evaluated 2 and 24 hours after removal of 40 minutes of coronary occlusion by morphometric analysis and 111In-labeled PMN infiltration. The administration of two structurally unrelated platelet-activating factor-receptor antagonists (SDZ 63-675, 5 mg/kg body weight, and WEB 2170, 5 mg/kg body weight) before reperfusion significantly reduced the accumulation of PMN, as well as the hemodynamic alterations and the size of necrotic area. Two hours after reperfusion, the percentage of increase of 111In-labeled PMN in transmural central ischemic zone was significantly reduced in rabbits pretreated with SDZ 63-675 (51.4 +/- 7.9) or WEB 2170 (32.4 +/- 8.8) with respect to untreated rabbits (107.6 +/- 13.5). The morphometric analysis of myocardial sections confirmed the reduction of PMN infiltration at 2 hours and demonstrated that at 24 hours the phenomenon was even more significant. In addition, SDZ 63-675 and WEB 2170 prevented early transient bradycardia and hypotension and reduced the infarct size, judged by staining with tetrazolium at 2 and 24 hours after reperfusion, and by histological examination at 24 hours. These results suggest that platelet-activating factor is involved in the accumulation of PMN in the reperfused ischemic myocardium and contributes to the evolution of myocardial injury.
Montrucchio
G
G
Dipartimento di Fisiopatologia Clinica, Ospedale Maggiore di S. Giovanni Battista e della Città di Torino, Italy.
Alloatti
G
G
Mariano
F
F
Comino
A
A
Cacace
G
G
Polloni
R
R
De Filippi
P G
PG
Emanuelli
G
G
Camussi
G
G
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002465:Cell Movement; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology; D011817:Rabbits; D012307:Risk Factors; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D011804:Quinolines; D014230:Triazoles; C053130:SRI 63-675; C063964:bepafant