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Role of platelet-activating factor in polymorphonuclear neutrophil recruitment in reperfused ischemic rabbit heart
G Montrucchio1, G Alloatti, F Mariano
1Dipartimento di Fisiopatologia Clinica, Ospedale Maggiore di S. Giovanni Battista e della Città di Torino, Italy.
Abstract:
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.
Insights
Platelet-activating factor (PAF) antagonists reduced polymorphonuclear neutrophil (PMN) infiltration in rabbit hearts after ischemia and reperfusion. This intervention also lessened cardiac injury, suggesting PAF’s role in myocardial damage.
Area of Science:
- Cardiovascular Research
- Inflammation and Immunology
- Pharmacology
Background:
- Cardiac ischemia and reperfusion injury involves inflammatory responses.
- Polymorphonuclear neutrophils (PMN) play a key role in myocardial damage following reperfusion.
- Platelet-activating factor (PAF) is implicated in inflammatory cell recruitment.
Purpose of the Study:
- To investigate the role of PAF in PMN recruitment during cardiac ischemia-reperfusion.
- To evaluate the therapeutic potential of PAF receptor antagonists in mitigating myocardial injury.
Main Methods:
- A rabbit model of 40-minute coronary occlusion followed by reperfusion was utilized.
- PMN accumulation was assessed using morphometric analysis and 111In-labeled PMN infiltration.
- The effects of two PAF receptor antagonists (SDZ 63-675 and WEB 2170) were evaluated.
Main Results:
- Pretreatment with PAF antagonists significantly reduced PMN infiltration at 2 and 24 hours post-reperfusion.
- Antagonists also attenuated hemodynamic alterations, including bradycardia and hypotension.
- Myocardial infarct size was significantly reduced in rabbits treated with PAF antagonists.
Conclusions:
- Platelet-activating factor is critically involved in PMN accumulation in the reperfused ischemic myocardium.
- Blocking the PAF receptor offers a promising therapeutic strategy to reduce myocardial injury and inflammation.
- These findings highlight PAF as a key mediator in the pathophysiology of cardiac ischemia-reperfusion damage.