The effect of cyclo-oxygenase and thromboxane synthetase inhibitors on shock induced by injection of heterologous blood in cats

The injection of rabbit blood into cats causes hypotension, thrombocytopaenia, leukopaenia, a rise in central venous pressure and right ventricular and pulmonary artery pressures and a fall in circulating levels of fibrinogen. Death occurred rapidly after injection of the rabbit blood in 50% of control animals and was associated with respiratory distress. Measurement of plasma thromboxane B 2 and 6-oxo PGF 1α levels in surviving controls demonstrated a marked elevation in the former with no significant change in the latter. Pretreatment with either the thromboxane synthetase inhibitor, 1-(cyclo octyl methyl) imidazole or aspirin prevented respiratory distress and death and reduced or prevented the elevations in cardiovascular pressures observed in control animals. Neither compound prevented thrombocytopaenia or leukopaenia but did attenuate the rise of thromboxane B 2 following injection of rabbit blood. In addition, pretreatment with 1-(cyclo octyl methyl) imidazole resulted in an approximately five-fold increase in circulatory levels of 6-oxo PGF 1α five minutes after inducing the shock. We conclude that thromboxane A 2 plays an important role in pulmonary (and other organs) dysfunction during the shock induced by injection of heterologous blood. In addition we have shown that inhibition of thromboxane synthetase in vivo under conditions where thromboxane A 2 is produced leads to an increase in the synthesis of prostacyclin.