Evidence for a role of platelet activating factor in hypovolemic shock in the rat

An extremely severe circulatory shock was produced in two different manners in urethane-anaesthetized rats in order to evaluate the key role of platelet-activating factor (PAF) and myocardial depressant factor (MDF) in low flow states. Haemorrhagic shock was induced by intermittently withdrawing about 50% of the estimated blood volume until mean arterial blood pressure (MAP) stabilized in the range of 20-25 mmHg. Vehicle-treated shocked rats died within 20-30 min after the last bleeding and exhibited elevated plasma activity of MDF (159.6 +/- 7.4 U/ml). Treatment with a specific PAF receptor antagonist, L-659,989, at doses of 500 or 1000 nmol/kg i.v., significantly increased survival rate, blunted the rise in plasma MDF activity and maintained MAP at higher values compared to vehicle shocked rats. Similarly, in another group of rats PAF (15 nmol/kg, i.v.) produced a shock-like state characterized by a serious hypotension in the range of 20-30 mmHg, elevated plasma MDF activity (79.7 +/- 7,7 U/ml) and death within 20-25 min after administration. L-659,989, given 5 min after the PAF-induced sharp decrease of MAP, improved survival rate, ameliorated MAP and reduced plasma levels of MDF. The results of this study, therefore, confirm that PAF plays a role in cardiovascular changes of hypovolemic circulatory shock both directly and by inducing the release of other factors such as MDF.