Although some investigators have shown a comparison of the neuroprotective effects of thiopental sodium and propofol, those comparisons were not quantitative. Therefore, in the present study, the neuroprotective effects of thiopental sodium, propofol, and halothane (for a control) were quantitatively evaluated. With use of a logistic regression curve, P50, which is the ischemic time and the duration of ischemic depolarization necessary for causing 50% neuronal damage in CA1 neurons, was estimated.
Methods
Sixty-three male gerbils were used. In the thiopental group (n=21), thiopental sodium was continuously infused intravenously at a rate of 2.0 mg kg-1 min-1, which produced a burst suppression pattern of electroencephalography in 25.3±3.4 mins. The infusion was stopped when reperfusion was initiated. In the propofol group (n=21), propofol was continuously infused intravenously at a rate of 2.0 mg kg-1 min-1, which produced a similar pattern of burst suppression in 29.7±11.5 mins. The infusion was continued until 30 mins after the reperfusion because of the shorter half-life of propofol than that of thiopental sodium. In the halothane group (n=21), halothane anesthesia was maintained at 1%. After confirmation of a burst suppression pattern, brain ischemia was initiated by occlusion of bilateral common carotid arteries for a pre-determined duration (3, 5 or 10 minutes, in 7 animals for each duration). During the experimental period, direct current (DC)-potentials were measured in bilateral CA1 regions, in which histological evaluation was performed 5 days later. Brain-surface and rectal temperature were monitored and maintained at 37.0±0.5 C.
Results
Percentages of neuronal damage following 5 minutes of ischemia in the thiopental, propofol and halothane groups were 3.3±4.7%, 22.7±25.2% and 62.7±25.1%, respectively. The logistic regression curves showed close relationships between percentage of neuronal damage and ischemic time (halothane, r2=.71, p<.0001; propofol, r2=.86, p<.0001; thiopental, r2=.88, p<.0001). With use of these curves, P50 of ischemic time in the halothane, propofol and thiopental groups were estimated to be 5.1 minutes, 6.5 minutes and 8.4 minutes, respectively. Onset time of ischemic depolarization was significantly prolonged in both the thiopental group (2.3±0.3 minutes, p<.0001) and propofol group (2.4±0.4 minutes, p<.0001) groups compared with that in the halothane group (1.8±0.3 minutes). The logistic regression curves also showed close relationships between percentage of neuronal damage and duration of ischemic depolarization (halothane, r2=.77, p<.0001; propofol, r2=.85, p<.0001; thiopental, r2=.86, p<.0001). With use of these curves, P50 of ischemic depolarization in the halothane, propofol and thiopental groups were estimated to be 6.4 minutes, 7.7 minutes and 9.6 minutes, respectively.
Conclusions
We quantitatively evaluated the neuroprotective effects of thiopental sodium, propofol, and halothane on brain ischemia. P50 of ischemic time was prolonged by 3.3 minutes and 1.4 minutes in the thiopental and propofol groups, respectively, compared with that in the halothane group. Onset time was prolonged by 0.5 minutes and 0.6 minutes in the thiopental and propofol groups, respectively, compared with that in the halothane group. P50 of ischemic depolarization was prolonged by 3.2 minutes and 1.3 minutes in the thiopental and propofol groups, respectively, compared with that in the halothane group.