Autonomic mechanisms in the age-related hypotensive effect of propofol.
We hypothesized that age-related differences in cardiovascular regulatory processes play a role in the augmented vasodepressor response to anesthetic induction with propofol in older subjects. To test this hypothesis, differences in baroreceptor responsiveness (BR) were first demonstrated in young adult (6-12 mo, n=12) and aged (>42 mo, n=12) New Zealand rabbits, and then the vasodepressor effect of propofol was compared in both the absence and presence of ganglionic blockade. For each age group, half of the animals were pretreated with 20 mg/kg IV hexamethonium (HEX) with the remaining half designated as controls. BR was first assessed by plotting cardiac cycle length as a function of the decline in mean arterial blood pressure (MAP) produced by multiple IV boluses of tri-nitroglycerine. Propofol was then given as an IV bolus of 4.5, 6.4, or 8.4 mg/kg over 3 s. Each animal was studied three times, receiving a single dose in variable order with at least 7 days between injections. In control animals, marked age-related differences in BR were evident and propofol produced larger peak decreases in MAP in older rabbits at all doses. HEX pretreatment abolished BR for both young and aged rabbits. However, after HEX administration the vasodepressor response to propofol in young animals was enhanced by 150% at 4.5, 125% at 6.4, and 61% at 8.4 mg/kg, respectively, whereas the impact in aged animals was only 25%, 30%, and -10%, respectively. These data support the hypothesis that age-related enhancement of propofol-induced hypotension is largely a reflection of diminished BR.
Memtsoudis
Stavros G
SG
Departments of *Anesthesiology and †Pharmacology, Weill Medical College of Cornell University, New York, NY.
The
Andrew H S
AHS
Heerdt
Paul M
PM
D000375:Aging / Q000502:physiology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D011817:Rabbits
D018686:Anesthetics, Intravenous; D005730:Ganglionic Blockers; D018738:Hexamethonium; D015742:Propofol