A pharmacological study of the cardiovascular effects of TRH-T in haemorrhagic shock in rats.

An extremely severe hypovolemic shock was produced in urethane-anesthetized rats by massive bleeding. In such preterminal conditions (mean arterial pressure = 19-25 mmHg; pulse pressure = 10-18 mmHg; death of all saline-treated animals in 26.16 +/- 3.18 min) the i.v. injection of protirelin tartrate (TRH-T) within 5 min after shock induction promptly and dose-dependently improved arterial pressure, pulse pressure and respiration, the dose of 4 mg/kg ensuring survival for 402.01 +/- 39.45 min without the need for the restoration of blood volume. The injection of TRH-T 20 min after shock induction, on the other hand, was ineffective. The concurrent administration of morphine (2.5 mg/kg i.v.) partially antagonized the effect of TRH-T; however, if the dose of the peptide was increased, its effect was restored. The effect of TRH-T in haemorrhagic shock was associated with a significant increase in the volume of residual circulating blood. The present data (i) confirm that TRH-T improves cardiovascular function and greatly prolongs survival in an otherwise irreversible model of haemorrhagic shock; (ii) show that this effect is associated with mobilization of residual blood and that respiratory function is greatly improved as well; (iii) indicate that the anti-shock effect of TRH-T is partially antagonized by morphine in a surmountable way. Finally, on the basis of our results, it appears that TRH-T has to be given rapidly after shock induction to be effective.