Transient ventilatory responses to endotoxin infusion in the cat are mediated by thromboxane A2

We tested the hypothesis that ventilatory responses to endotoxin infusion in the anesthetized cat are mediated by thromboxane A2 (TxA2). Intravenous infusion of endotoxin (1.6 mg/kg of E. coli, strain 05:B55, delivered over 1 min) in six cats elicited increases in right ventricular blood pressure (Prv) and a transient systemic hypotension. These hemodynamic changes were accompanied by an abrupt apnea, followed by a transient period of rapid, shallow breathing, Cardiorespiratory changes coincided with large increases (> 10-fold) in the plasma concentration of TxB2, the stable metabolite of TxA2. These effects and the release of TxA2 did not occur if endotoxin was infused a second time into the same animal. In addition, animals that were pretreated with either indomethacin (n = 3; 3.0 mg/kg) or the TxA2 receptor antagonist, daltroban, (n = 4; 7.5 mg/kg) exhibited no change in Prv, arterial blood pressure, or respiration when given equivalent doses of endotoxin. We conclude that the release of TxA2 is responsible for the early pulmonary hypertension and rapid, shallow breathing observed during endotoxin infusion in the anesthetized cat. These TxA2-mediated responses are severe but transient in nature.