Hemodynamic effects of di-sec-butyl phenol, an anesthetic substituted phenol.

Dose- and age-related hemodynamic effects were determined for an anesthetic substituted phenol, 2,6-di-sec-butyl phenol (DSB). DSB, 7.5 mg/kg, induced hypnosis in young rabbits and increased mean blood pressure to 170 +/- 14% and heart rate to 150 +/- 21% of control values. In elderly rabbits, 7.5 mg/kg DSB induced hypnosis, had no effect on blood pressure, but increased the heart rate to 130 +/- 2% of control. After ganglionic blockade with hexamethonium, 7.5 mg/kg DSB caused a decline in mean blood pressure (71 +/- 5% of control) without change in heart rate. DSB increased norepinephrine release from SH-SY5Y cells, a human neuroblastoma cell line (5.4 +/- 1.7% vs. 3.5 +/- 0.3%). DSB produced age-dependent elevation of mean blood pressure in rabbits, probably by causing release of catecholamines from the sympathetic nervous system.

Anesthetic-induced alteration in expression of myocardial calcium cycling proteins.

OBJECTIVE: The purpose of this study was to test the hypothesis that anesthesia alone or in combination with high F(I)(O)2 alters expression of the myocardial calcium cycling proteins, sarcoplasmic endoreticular calcium adenosine triphosphatase subtype 2a (SERCA2a), and the sarcolemmal sodium-calcium exchanger (NCX). DESIGN: Multigroup comparison of protein expression using analysis of variance. SETTING: University research laboratory. SUBJECTS: Twenty-seven New Zealand white rabbits. INTERVENTIONS: After sedation and the induction of anesthesia, animals underwent either tracheal intubation and ventilation for 5 hours with 1.0% end-tidal halothane in oxygen (HAL-O(2) , n = 5) or air (HAL-air, n = 5) or time-control recovery while spontaneously breathing oxygen (TC-O(2) , n = 5) or air (TC-air, n = 5) for 5 hours. Halothane dose was based on pilot data from 2 rabbits. Animals were then sacrificed, and the hearts were removed for Western blot analysis. Data were normalized to those from a group of rabbits immediately sacrificed (n = 5) without any prior treatment. MEASUREMENTS AND MAIN RESULTS: In comparison to their respective time controls, SERCA2a was decreased 23 % in both HAL-air and HAL-O(2) groups, whereas NCX was increased 34% and 122%, respectively. Expression was distinctly different between HAL-air and HAL-O(2) for both SERCA2a (p = 0.009) and NCX (p < 0.001), indicating an influence of high F(I)O(2). Similarly, SERCA2a in the TC-O(2) group was reduced 25% relative to the TC-air group. CONCLUSION: Halothane alters the expression of myocardial calcium cycling proteins, and this effect is potentiated by high F(I)O(2) . These data offer the broad conclusion that perioperative interventions may influence the study of myocardial molecular remodeling and suggest the possibility of anesthetic-induced myocardial molecular remodeling.

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.