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Platelet-activating factor (PAF) induces platelet/neutrophil co-operation during myocardial reperfusion
G Alloatti1, G Montrucchio, G Emanuelli
1Dipartimento di Biologia Animale, Ospedale S. Luigi Gonzaga, Torino, Italy.
Abstract:
The purpose of this study was to evaluate the role of platelet-activating factor (PAF) in cardiac dysfunctions occurring in ischemic isolated rabbit heart reperfused in the presence of polymorphonuclear neutrophils (PMN) and platelets (PLT). In a first set of experiments two different PAF-receptor antagonists were used to investigate the role of endogenous PAF released in the coronary vessels of post-ischemic heart. Mechanical and electrical dysfunctions occurring during reperfusion of ischemic heart were worsened in the presence of both PMN and PLT. Co-operation between PMN and PLT was suggested by the absence of effect when reperfusion was done with PMN alone, and by the significant enhancement of the effect of PLT after addition of PMN. The activation of PMN and PLT was mediated by PAF, since it was prevented by receptor antagonists SDZ 63-675 (3 x 10(-6)M) and WEB 2170 (3 x 10(-6)M). In a second set of experiments, the infusion of PAF in non-ischemic rabbit heart perfused with PMN and PLT was used to evaluate whether PAF can induce PMN-PLT interaction and reproduce the effects of ischemia. In this condition, the infusion of synthetic PAF (1 x 10(-7)M) induced mechanical and electrical dysfunctions similar to that occurring during reperfusion. The protective effect of both PAF receptor antagonists (SDZ 63-675 and WEB 2170) and of a leukotrienes receptor antagonist (FPL 55712, 1 x 10(-6)M) suggested that PAF is the mediator that triggers the co-operation between PMN and PLT, while leukotrienes produced by these cells are the final effector of cardiac dysfunction. In conclusion, these results suggested that PAF released during reperfusion of ischemic rabbit heart may amplify mechanical and electrical dysfunctions by triggering PMN-PLT co-operation.
Insights
Platelet-activating factor (PAF) amplifies cardiac dysfunction during heart reperfusion by triggering interactions between neutrophils (PMN) and platelets (PLT). Blocking PAF prevents these harmful effects, highlighting its role in post-ischemic heart damage.
Area of Science:
- Cardiovascular Research
- Inflammation and Immunology
- Pharmacology
Background:
- Ischemia-reperfusion injury can lead to significant cardiac dysfunction.
- Polymorphonuclear neutrophils (PMN) and platelets (PLT) are implicated in exacerbating cardiac damage during reperfusion.
- The precise role of platelet-activating factor (PAF) in mediating PMN-PLT interactions and subsequent cardiac dysfunction requires further elucidation.
Purpose of the Study:
- To evaluate the role of platelet-activating factor (PAF) in cardiac dysfunctions during the reperfusion of ischemic isolated rabbit hearts.
- To investigate the mechanism by which PAF influences the interaction between PMN and PLT in the context of cardiac ischemia-reperfusion.
- To determine if PAF can induce cardiac mechanical and electrical dysfunctions independently and if its effects can be mitigated by receptor antagonists.
Main Methods:
- Utilized isolated rabbit heart models subjected to ischemia and reperfusion.
- Administered PAF-receptor antagonists (SDZ 63-675, WEB 2170) to assess the role of endogenous PAF.
- Infused synthetic PAF into non-ischemic hearts perfused with PMN and PLT to mimic ischemia-reperfusion effects and tested leukotriene receptor antagonists (FPL 55712).
Main Results:
- Mechanical and electrical cardiac dysfunctions were worsened by the presence of both PMN and PLT during reperfusion.
- PAF was identified as the mediator triggering PMN-PLT co-operation, as PAF-receptor antagonists prevented the exacerbation of cardiac dysfunction.
- Synthetic PAF infusion induced cardiac dysfunctions similar to ischemia-reperfusion, and leukotriene receptor antagonists suggested leukotrienes as final effectors.
Conclusions:
- PAF released during ischemic rabbit heart reperfusion amplifies cardiac mechanical and electrical dysfunctions.
- PAF triggers a co-operative interaction between PMN and PLT, contributing significantly to post-ischemic cardiac damage.
- Targeting PAF and downstream mediators like leukotrienes may offer therapeutic strategies for mitigating ischemia-reperfusion injury.