Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits

Abstract

Purpose: To elucidate mechanisms by which remifentanil, an ultra-short-acting μ-opioid receptor agonist, causes hypotension and bradycardia. Methods: Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were measured and recorded after bolus injections of 1, 2 or 5 μg · kg-1 of remifentanil in neuraxis intact (n=6 for each dose) and baro-denervated rabbits (n=6 for each dose). Arterial baroreflex sensitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 μg · kg-1 after pretreatment with naloxone, 40 μg · kg-1. Results: All values were expressed in % change from baseline. In the neuraxis intact animals, MAP and HR were decreased briefly immediately after remifentanil injection. RSNA was increased dose-dependently: 137 ± 8% (mean ± SE), 170 ± 14% (P < 0.05) and 225 ± 29% (P < 0.05) after 1, 2 and 5 μg · kg-1 remifentanil, respectively. RSNA was increased even after MAP and HR had returned to baseline values. The depressor tests revealed that remifentanil did not attenuate arterial baroreflex sensitivity. In the baro-denervated animals, MAP and HR decreased gradually to 77 ± 3% (P < 0.05) and 94 ± 1% (P < 0.05), respectively 300 sec after 5 μg · kg-1 remifentanil. At that time, increased RSNA (159 ± 9%, P < 0.05) had returned to baseline. Pretreatment with naloxone in the baro-denervated animals abolished these changes. Conclusion: Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral μopioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.