Introduction. After a blood loss of approximately 30% of the total blood volume a widespread sympathoinhibition results in hypotension and bradycardia. We have previously shown that the unselective opioid receptor antagonist naloxone delays this so called decompensatory phase of hemorrhage in conscious sheep (Frithiof & Rundgren 2006). Here we investigate the contribution of the individual opioid receptor subtypes.

Methods. Adult conscious ewes were continuously bled from a jugular vein until mean arterial blood pressure reached 50 mmHg. Starting 30 min before hemorrhage ICI 174.864 (delta-rec antagonist, 0.8 mg/h), nor-BNI (kappa-rec antagonist, 0.24 mg/h) or CTOP (mu-rec antagonist, 0.12 mg/h)were infused intracerebroventricularly (ICV). Control experiments using artificial cerebrospinal fluid (aCSF) were performed on each animal.

Results. Compared to aCSF nor-BNI and ICI 174.864 significantly increased the blood loss necessary to initiate the decompensatory phase (18.9 ± 2.3 vs 14.2 ± 1.5 ml/kg, n = 6 and 18.4 ± 3.4 vs 15.3 ± 2.1 ml/kg, n = 6, respectively). CTOP did not significantly alter hemorrhage volumes compared to aCSF (12.3 ± 4.2 vs 14.7 ± 2.1 ml/kg, n = 6).

Conclusion. Blockade of cerebral kappa and delta opioid receptors delays but does not prevent the onset of hypotension and bradycardia during a continuous hemorrhage. This suggest that both kappa and delta opioid receptors at sites accessible from the cerebral ventricles are important in initiating the decompensatory phase but other mediators than opioids are probably involved as well.

REFERENCE

Frithiof, R. & Rundgren, M. 2006. Am J Physiol Regul Integr Comp Physiol [Epub ahead of print]