TRANSIENT VENTILATORY RESPONSES TO ENDOTOXIN INFUSION IN THE CAT ARE MEDIATED BY THROMBOXANE-A(2)

We tested the hypothesis that ventilatory responses to endotoxin infus ion in the anesthetized cat are mediated by thromboxane A2 (TxA2). Int ravenous infusion of endotoxin (1.6 mg/kg of E. coli, strain 05:B55, d elivered over 1 min) in six cats elicited increases in right ventricul ar blood pressure (Prv) and a transient systemic hypotension. These he modynamic changes were accompanied by an abrupt apnea. followed by a t ransient period of rapid, shallow breathing. Cardiorespiratory changes coincided with large increases (> 10-fold) in the plasma concentratio n of TxB2, the stable metabolite of TxA2. These effects and the releas e of TxA2 did not occur if endotoxin was infused a second time into th e same animal. In addition, animals that were pretreated with either i ndomethacin (n = 3; 3.0 mg/kg) or the TxA2 receptor antagonist, daltro ban, (n = 4; 7.5 mg/kg) exhibited no change in Prv, arterial blood pre ssure, or respiration when given equivalent doses of endotoxin. We con clude that the release of TxA2 is responsible for the early pulmonary hypertension and rapid, shallow breathing observed during endotoxin in fusion in the anesthetized cat. These TxA2-mediated responses are seve re but transient in nature.