The effects of aspirin and methysergide, singly and in combination, on systemic haemodynamic responses to pulmonary...

Pretreatment of anaesthetized rabbits with aspirin (A), 250 mg.kg-1, methysergide (M) 3 mg.kg-1 or a combination of both (A + M) was done before pulmonary embolism with a 1.0 ml autologous blood clot and compared with no pretreatment (C). Experiments were done until 10 survivors were present in each group. Mortality rate in controls (C) was 55 per cent (death in less than 30 minutes) compared to zero in (A) and (A + M) and nine per cent in (M). Arterial blood pressure fell to 60 per cent of pre-embolism values two minutes after embolism in (C) but had returned to 85 per cent of pre-embolism values after 60 minutes. This compares with a drop to 82 per cent at two minutes and 83 per cent at 60 minutes in (A), a drop to 70 per cent at two minutes and 90 per cent at 60 minutes in (M) and a very small drop to 92 per cent at two minutes which was unchanged at 60 minutes in (A + M). Right ventricular pressure increased by 75 per cent after two minutes compared to pre-embolism values in (C) and was still elevated by 37 per cent after 60 minutes. This compares with increases at two minutes and 60 minutes respectively of 58 and 23 per cent in (A), 65 and 35 per cent in (M) and 55 and 18 per cent in (A + M). Heart rate did not show any significant changes in any of the groups after embolism. These results show a dramatic reduction in mortality from pulmonary embolism with aspirin or methysergide pretreatment, which is associated with significant attenuation of the hypotensive response seen in controls. These agents may act by inhibiting the actions of a release of prostaglandins and serotonin. The additive effects of the combination used suggests that both mediators may play a role in the haemodynamic responses to pulmonary embolism.