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Cardiac ultrastructural effects of the platelet-activating factor and its antagonist BN 52021
1Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
Insights
Platelet-activating factor causes ultrastructural damage in guinea pig hearts, leading to myocardial ischemia. BN 52021 pretreatment prevented these harmful effects, suggesting a therapeutic target.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Pathophysiology
Background:
- Platelet-activating factor (PAF) is implicated in various cardiovascular conditions.
- Understanding PAF's direct effects on myocardial ultrastructure is crucial for elucidating ischemia mechanisms.
Purpose of the Study:
- To investigate the ultrastructural changes in myocardium induced by PAF.
- To assess the protective effects of BN 52021 against PAF-induced cardiac damage.
Main Methods:
- Isolated perfused guinea pig heart model.
- Electron microscopy to observe cellular and subcellular changes.
- Lanthanum tracer studies to assess vascular permeability.
- Enzyme activity assays for mitochondrial function.
Main Results:
- PAF induced capillary dilation with platelet aggregation and pericapillary edema.
- Myocardial cells showed intracellular edema, myofibrillar alterations, and mitochondrial damage.
- Increased intracellular and mitochondrial calcium deposits were observed.
- Decreased mitochondrial enzyme activities (cytochrome oxidase, succinic dehydrogenase) and altered permeability were noted.
- BN 52021 completely abolished PAF-induced morphological alterations.
Conclusions:
- PAF triggers vascular and ischemic-like cellular damage in the myocardium.
- These PAF-induced changes are significant in the pathophysiology of myocardial ischemia.
- BN 52021 demonstrates potential as a protective agent against PAF-mediated cardiac injury.
Abstract:
Platelet-activating factor-induced ultrastructural changes of myocardium were examined in isolated perfused guinea pig heart. The platelet-activating factor (10(-9)-10(7) M) caused the following electron microscopic changes: a) dilated capillaries filled with platelets and aggregated platelets. The endothelial cells adjoining the platelets remained uninjured but pericapillary oedema was observed. b) in the myocardium intracellular oedema, myofibrillar alterations, decrease of matrix density and rupture of crest in mitochondria can be seen. c) Ca2+ deposits in the cytoplasm increased and appeared in mitochondria, too. d) the intramitochondrially localised cytochromoxydase and succinic dehydrogenase activities were decreased. e) using lanthanum tracer permeability alterations were observed. Pretreatment with BN 52021 (10(6) M) completely prevented the morphological effects of the platelet-activating factor. From these results we conclude that the platelet-activating factor-induced vascular and ischemic like cellular damage appear to play an important role in the pathophysiology of myocardial ischemia.