MECHANISMS WHEREBY PROPOFOL MEDIATES PERIPHERAL VASODILATION IN HUMANS - SYMPATHOINHIBITION OR DIRECT VASCULAR RELAXATION

Background: Anesthetic induction and maintenance with propofol are ass ociated with decreased blood pressure that is, in part, due to decreas ed peripheral resistance. Several possible mechanisms whereby propofol could reduce peripheral resistance include a direct action of propofo l on vascular smooth muscle, an inhibition of sympathetic activity to the vasculature, or both, This study examined these two possibilities in humans by measuring the forearm vascular responses to infusions of propofol into the brachial artery (study 1) and by determining the for earm arterial and venous responses to systemic (intravenous) infusions of propofol after sympathetic denervation of the forearm by stellate blockade (study 2). Methods: Bilateral forearm venous occlusion plethy smography was used to examine forearm vascular resistance (FVR) and fo rearm vein compliance (EVC), Study 1 used infusion of intralipid (time control) and propofol at rates between 83 and 664 mu g/min into the b rachial artery of 11 conscious persons and compared responses to arter ial infusions of sodium nitroprusside (SNP) at 0.3, 3.0, and 10 mu g/m in. Venous blood from the infusion arm was assayed for plasma propofol concentrations, In study 2, after left stellate block (12 ml 0.25% bu pivacaine + 1% lidocaine), six participants were anesthetized and main tained with propofol infusions of 125 and 200 mu g . kg(-1). min(-1). Simultaneous right forearm (unblocked) blood flow dynamics served as t he time control, In three additional conscious participants, intrabrac hial artery infusions of SNP and nitroglycerin, both at 10 mu g/min, w ere performed before and after stellate blockade of the left forearm t o determine whether the sympathetically denervated forearm vessels cou ld dilate beyond the level produced by denervation alone. Results: In study 1, infusion of intralipid or propofol into the brachial artery d id not change EVR or FVC, Sodium nitroprusside significantly decreased FVR in a dose-dependent manner by 22 +/- 5%, 65 +/- 3%, and 78 +/- 2% (mean +/- SEM) but did not change FVC, During the incremental propofo l infusions, plasma propofol concentrations increased from 0.2 to 10.1 mu g/ml and averaged 7.4 +/- 1.1 mu g/ml during the highest infusion rate, In study 2, stellate ganglion blockade decreased FVR by 50 +/- 6 % and increased FVC by 58 +/- 10%, Propofol anesthesia at 125 and 200 mu g . kg(-1). min(-1) progressively reduced mean arterial pressure. I n the arm with sympathetic denervation, FVR and FVC showed no further changes during propofol anesthesia, whereas in the control arm FVR sig nificantly decreased by 41 +/- 9% and 42 +/- 7%, and FVC increased sig nificantly by 89 +/- 27% and 85 +/- 32% during 125 and 200 mu g . kg(- 1). min(-1) infusions of propofol, respectively, In the three addition al conscious participants, intraarterial infusion of SNP and nitroglyc erin (TNG) after the stellate blockade resulted in a further decrease of FVR and a further increase of FVC, Conclusions: In contrast to SNP infusions, propofol infusions into the brachial artery of conscious pe rsons caused no significant vascular responses, despite the presence o f therapeutic plasma concentrations of propofol within the forearm, Th e effects of propofol anesthesia on EVR and FVC are similar to the eff ects of sympathetic denervation by stellate ganglion blockade, Thus th e peripheral vascular actions of propofol appear to be due primarily t o an inhibition of sympathetic vasoconstrictor nerve activity.