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Effect of methysergide pretreatment on thrombin-induced pulmonary oedema in the rat
Abstract:
Microembolic pulmonary oedema was induced by injection of thrombin (500 NIH units/kg body weight) i.v. in rats in which fibrinolysis had been inhibited by pretreatment with trans-4-aminomethyl-cyclohexanoid-carboxylic acid (AMCA). To evaluate the role of serotonin in this condition the effect of pretreatment with the antiserotonin compound methysergide (2.5 mg/kg body weight) on the amount of pulmonary oedema was studied. Pretreatment with methysergide resulted in a 20% decrease in lung weight in thrombin-treated rats. It caused a significant reduction of dilated lymph vessels, and of interstitial and alveolar oedema, as evaluated morphometrically. Methysergide pretreatment did not significantly alter the number of degranulated mast cells. Antiserotonin is thought to exert its effect by lowering the filtration pressure in the pulmonary microcirculation.
Insights
This study investigated serotonin's role in microembolic pulmonary edema. Antiserotonin methysergide reduced lung weight and edema, suggesting serotonin contributes to this condition.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Pathophysiology
Background:
- Microembolic pulmonary edema is a serious condition.
- Serotonin's involvement in pulmonary edema is not fully understood.
- Fibrinolysis inhibition can exacerbate pulmonary edema.
Purpose of the Study:
- To investigate the role of serotonin in microembolic pulmonary edema.
- To evaluate the efficacy of the antiserotonin methysergide in reducing pulmonary edema.
- To assess the impact of methysergide on pulmonary microcirculation and edema markers.
Main Methods:
- Induction of microembolic pulmonary edema in rats using thrombin.
- Inhibition of fibrinolysis using trans-4-aminomethyl-cyclohexanoid-carboxylic acid (AMCA).
- Administration of methysergide (antiserotonin) prior to thrombin injection.
- Morphometric evaluation of lung weight, lymph vessels, and interstitial/alveolar edema.
Main Results:
- Methysergide pretreatment decreased lung weight by 20% in thrombin-treated rats.
- Significant reduction in dilated lymph vessels, interstitial, and alveolar edema observed.
- Methysergide did not significantly alter degranulated mast cell counts.
- Antiserotonin action is hypothesized to reduce pulmonary microcirculation filtration pressure.
Conclusions:
- Serotonin plays a significant role in the development of microembolic pulmonary edema.
- Methysergide demonstrates a protective effect against thrombin-induced pulmonary edema.
- Targeting serotonin pathways may be a therapeutic strategy for pulmonary edema.