Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits

Purpose: To elucidate mechanisms by which remifentanil, an ultra-short-acti ng mu-opioid receptor agonist, causes hypotension and bradycardia. Methods: Mean arterial pressure (MAP), heart rate (HR) and renal sympatheti c nerve activity (RSNA) were measured and recorded after bolus injections o f 1, 2 or 5 mu g.k(-1) of remifentanil in neuraxis intact (n=6 for each dos e) and baro-denervated rabbits (n=6 for each dose). Arterial baroreflex sen sitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 mu g.k(-1) after pretreatment with naloxo ne, 40 mu g.kg(-1). Results: All values were expressed in % change from baseline. In the neurax is intact animals, MAP and HR were decreased briefly immediately after remi fentanil 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 mu g.kg(-1) remifentanil, respectively. RSNA was increased even after MAP a nd HR had returned to baseline values. The depressor tests revealed that re mifentanil did not attenuate arterial baroreflex sensitivity. In the baro-d enervated animals, MAP and HR decreased gradually to 77 +/- 3% (P < 0.05) a nd 94 +/- 1% (P < 0.05), respectively 300 sec after 5 mu g.kg(-1) remifenta nil. At that time, increased RSNA (159 +/- 9%, P < 0.05) had returned to ba seline. Pre-treatment with naloxone in the baro-denervated animals abolishe d these changes. Conclusion: Remifentanil decreases HR and MAP by its central vagotonic effe ct and by stimulating peripheral mu-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by ma intaining arterial baroreflex integrity.