Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits.
OBJECTIVE
To elucidate mechanisms by which remifentanil, an ultra-short-acting mu-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 microg x 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 microg x kg(-1) after pretreatment with naloxone, 40 microg x 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 microg x 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 microg x 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.


CONCLUSIONS
Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral mu-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.
Shinohara
K
K
Department of Anesthesiology, University of Kansas Medical Center, Kansas City 66160-7415, USA.
Aono
H
H
Unruh
G K
GK
Kindscher
J D
JD
Goto
H
H
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000627:therapeutic use*; D011311:Pressoreceptors / Q000502:physiology*; D011817:Rabbits; D000077208:Remifentanil; D013564:Sympathetic Nervous System / Q000187:drug effects
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010880:Piperidines; D009270:Naloxone; D000077208:Remifentanil