Jae Young Kwon

Effects of temperature on cerebral tissue oxygen tension, carbon dioxide tension, and pH during transient global ischemia in rabbits

Background A decrease in brain temperature (Tbrain) causes a decrease in the cerebral metabolic rate for oxygen (CMRO2) and provides potent neuroprotection against ischemic damage. In the present study, the effects of mild to moderate hypothermia on cerebral tissue oxygen tension (PO2 brain), carbon dioxide tension (PCO2 brain), and pH (pHbrain) were monitored during short episodes of global cerebral ischemia. Methods After approval by the Animal Care and Use Committee, 10 New Zealand white rabbits were anesthetized (1% halothane in air) and mechanical ventilation was adjusted to maintain the arterial carbon dioxide tension at 35 mmHg (alpha‐stat). A sensor to measure PO2 brain, PCO2 brain, pHbrain, and Tbrain was inserted into the brain through a burr hole in the skull. Tbrain was adjusted to 38 [degree sign] Celsius, 34.4 [degree sign] Celsius, and 29.4 [degree sign] Celsius in a random sequence in each animal. PO2 brain, PCO sub 2 brain, and pHbrain (all variables are reported at the actual Tbrain) were recorded every 10 s during a 5‐min baseline, 3 min of cerebral ischemia induced by inflation of a neck tourniquet, and 10 min of reperfusion at each level of Tbrain. Analysis of variance and Dunnetts test were used for statistical analysis. Data are presented as means +/‐ SD. Results During ischemia, PO2 brain decreased from 56 +/‐ 3 to 33 +/‐ 2 mmHg at 38 [degree sign] Celsius, from 58 +/‐ 3 to 32 +/‐ 3 mmHg at 34.4 [degree sign] Celsius, and from 51 +/‐ 2 to 32 +/‐ 2 mmHg at 29.4 [degree sign] C (p = NS). PCO2 brain increased by 6.7 +/‐ 2 mmHg at 38 [degree sign] Celsius, by 5.1 +/‐ 1.4 mmHg at 34.4 [degree sign] Celsius, and by 2.3 +/‐ 0.8 mmHg at 29.4 [degree sign] Celsius. pH sub brain inversely followed the trend of PCO2 brain. Conclusions The attenuated increase in PCO2 brain during hypothermic ischemia results from the reduced CMRO2. The similar decrease in PO2 brain at all temperature levels indicates that despite the reduction in CMRO2, PO2 brain is no better preserved during brief episodes of hypothermic ischemia than during normothermic ischemia.

Riluzole does not attenuate increases in hippocampal glutamate concentrations in a rabbit model of repeated transient global cerebral ischemia.

The aim of the present study was to examine the ability of riluzole to inhibit glutamate release during episodes of transient global cerebral ischemia.New Zealand White rabbits (n = 36) were anesthetized with halothane and mechanically ventilated to maintain normocarbia. Microdialysis catheters were inserted bilaterally into the dorsal hippocampus and perfused with artificial cerebrospinal fluid at 2 micro L/min. Animals were randomly assigned to control, hypothermia (30[degree sign]C), or riluzole (2 or 8 mg/kg; R2 and R8) groups. Two episodes of transient global cerebral ischemia (each lasting 10 min) were produced by inflating the pneumatic tourniquet combined with induced hypotension. Dialysate was collected throughout the periischemic period, and glutamate concentrations were determined by using high-performance liquid chromatography. Peak levels were compared by using the Kruskal-Wallis test. Glutamate concentrations significantly increased by twofold to fourfold during the second ischemic period for the control, R2, and R8 groups. Glutamate concentrations in the hypothermic group were significantly lower than those in the other three groups and remained at baseline levels during the entire experiment. This study demonstrates that the sodium channel blocker riluzole does not inhibit ischemia-induced glutamate accumulation. The previously reported neuroprotective ability of riluzole may be caused by mechanisms other than the presynaptic inhibition of glutamate release during ischemia. Implications: Glutamate, an excitatory neurotransmitter, is released in excessive amounts during brain ischemia and may result in neuronal injury and death. Riluzole, a neuronal sodium channel blocker, has neuroprotective properties in some animal models of brain ischemia, possibly because of its ability to inhibit the release of glutamate from synaptic vesicles. However, this microdialysis study failed to demonstrate any attenuation of glutamate release during transient global ischemia after the administration of either 2 mg/kg or 8 mg/kg of riluzole.

Effects of pentobarbital and isoflurane on conditioned learning after transient global cerebral ischemia in rabbits.

BACKGROUND The acquisition of a conditioned eyeblink response has been used extensively to study the neurologic substrates of learning and memory. We examined the effects of the anesthetics isoflurane and pentobarbital, or hypothermia (30 degrees C), on the ability of rabbits to acquire an eyeblink conditioned response after 6.5 min of cerebral ischemia. METHODS New Zealand white rabbits (n = 48) were randomly assigned to sham, normothermic, hypothermic, isoflurane, or pentobarbital groups. In the normothermic, hypothermic, isoflurane, and pentobarbital groups, 6.5 min of global cerebral ischemia was produced. In animals randomized to the isoflurane and pentobarbital groups, a pattern of burst suppression was achieved on the electroencephalogram before the start of the ischemic episode. Animals in the hypothermia group were cooled to 30 degrees C before ischemia. Seven days after ischemia, eyeblink training was started using an audible tone presented for 100 ms as the conditioned stimulus. The unconditioned stimulus was an air puff directed at the cornea. The delay between the end of conditioned stimulus and the start of the unconditioned stimulus (the trace interval) was 300 ms in duration. A conditioned response was defined as an eyeblink that was initiated during the trace interval. Eighty trials per day and 15 days of training were delivered. RESULTS Neurologic deficits were greatest in the normothermia group, and these animals also had fewer conditioned responses than those in the sham, hypothermia, or pentobarbital groups. Animals in the isoflurane group had an intermediate number of conditioned responses that was not significantly different from the normothermia group. CONCLUSIONS This study demonstrates that a brief episode of cerebral ischemia results in the impairment of associative learning. Hypothermia and burst-suppressive doses of pentobarbital were able to improve neurobehavioral outcome as measured by ability to acquire a trace conditioned response.

Effects of hypothermia and lamotrigine on trace-conditioned learning after global cerebral ischemia in rabbits

Acquisition of the trace-conditioned eye blink response (CR) is mediated by a variety of brain structures, including the cerebellum, the hippocampus, and brain stem nuclei. We examined the effects of a neuronal sodium channel antagonist (lamotrigine) on the ability of rabbits to acquire an eye blink CR after 6.5 min of cerebral ischemia. New Zealand white rabbits (n = 31) were randomly assigned to sham (S), normothermic ischemia (N), hypothermic (30 degrees C) ischemia-(H), or lamotrigine (50 mg/kg) treated (L) groups. In the N, H, and L groups, 6.5 min of global cerebral ischemia was produced using an inflatable neck tourniquet. Trace conditioning was started on the 7th postischemic day. The conditioned stimulus consisted of a tone (85 dB, 6 kHz) presented for 100 ms. The unconditioned stimulus was an air puff (150 ms duration) directed at the cornea. The interval between the end of the conditioned stimulus and the start of the unconditioned stimulus (the trace interval, TI) was 300 ms in duration. A trace-conditioned response was defined as an eye blink that was initiated during the TI. Eighty trials were delivered daily for 15 days. Neurologic deficits were greatest in the N group, and these animals had fewer CRs (149 +/- 157) than animals in the S (509 +/- 214) or H (461 +/- 149) groups (P < 0.05 by analysis of variance). Animals in the L group had a total number of CRs (380 +/- 253) that was intermediate between the S and N groups. Histologic evidence of neural injury was greatest in the N group. This study demonstrates that a brief episode of cerebral ischemia results in the impairment of this test of neurobehavioral function. Both hypothermia and lamotrigine were able to attenuate the impairment of eye blink trace-conditioned responses produced by cerebral ischemia.

The effects of sevoflurane and propofol anesthesia on cerebral oxygenation in gynecological laparoscopic surgery

Background Both the Trendelenburg position and pneumoperitoneum with carbon dioxide have been reported to increase intracranial pressure (ICP) and to alter cerebral blood flow or cerebral blood volume. Also anesthetic agents have variable effects on cerebral hemodynamics and ICP. The present study was conducted to determine whether regional cerebral oxygen saturation (rSO2) values differ between propofol and sevoflurane anesthesia during laparoscopic surgery in the Trendelenburg position. Methods Thirty-two adult women undergoing gynecological laparoscopic surgery were divided into sevoflurane and propofol groups. rSO2 values were recorded at 10 min after induction in the neutral position (Tpre), 10 min after the pneumoperitoneum in the Trendelenburg position (Tpt) and 10 min after desufflation in the neutral position (Tpost). For analysis of rSO2, we did ANOVA and univariate two-way ANCOVA with covariates being mean arterial pressure and end tidal carbon dioxide tension. Results Between sevoflurane and propofol groups, the change in rSO2 was significantly different even after ANCOVA. rSO2 at Tpt (76.3 ± 5.9% in sevoflurane vs 69.4 ± 5.8% in propofol) and Tpost (69.5 ± 7.1% in sevoflurane vs 63.8 ± 6.6% in propofol) were significantly higher in the sevoflurane group compared with the propofol group. In the propofol group, rSO2 at Tpost was significantly lower than at Tpre (71.1 ± 4.8%) and cerebral oxygen desaturation occurred in two patients (14.3%). Conclusions Significantly lower rSO2 values were observed in the propofol group during gynecological laparoscopic surgery. The possibility of cerebral oxygen desaturation should not be overlooked during propofol anesthesia even after desufflation of the abdomen in the neutral position.

Comparison of patient-controlled epidural analgesia with patient-controlled intravenous analgesia for laparoscopic radical prostatectomy

Background Patient-controlled epidural analgesia (PCEA) is known to provide good postoperative analgesia in many types of surgery including laparoscopic surgery. However, no study has compared PCEA with patient-controlled intravascular analgesia (PCIA) in laparoscopic radical prostatectomy (LARP). In this study, the efficacy and side effects of PCEA and PCIA after LARP were compared. Methods Forty patients undergoing LARP were randomly divided into two groups: 1) a PCEA group, treated with 0.2% ropivacaine 3 ml and 0.1 mg morphine in the bolus; and 2) a PCIA group, treated with oxycodone 1 mg and nefopam 1 mg in the bolus. After the operation, a blinded observer assessed estimated blood loss (EBL), added a dose of rocuronium, performed transfusion, and added analgesics. The numeric rating scale (NRS), infused PCA dose, and side effects were assessed at 1, 6, 24, and 48 h. Results EBL, added rocuronium, and added analgesics in the PCEA group were less than those in the PCIA group. There were no significant differences in side-effects after the operation between the two groups. Patients were more satisfied with PCEA than with PCIA. The NRS and accumulated PCA count were lower in PCEA group. Conclusions Combined thoracic epidural anesthesia could induce less blood loss during operations. PCEA showed better postoperative analgesia and greater patient satisfaction than PCIA. Thus, PCEA may be a more useful analgesic method than PICA after LARP.

Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models

Background This study was conducted to investigate the pharmacodynamic interaction between rocuronium and cisatracurium using the response surface model, which is not subject to the limitations of traditional isobolographic analysis. Methods One hundred and twenty patients were randomly allocated to receive one of the fifteen predefined combinations of rocuronium and cisatracurium. To study single drugs, cisatracurium 0.2, 0.15, or 0.1 mg/kg or rocuronium 0.8, 0.6 or 0.4 mg/kg doses were administered alone. To study the pharmacodynamic interaction, drugs were applied in three types of combination ratio, i.e., half dose of each drug alone, 75% of each single dose of rocuronium and 25% of each single dose of cisatracurium, and vice versa. Train-of-four (TOF) ratio and T1% (first twitch of the TOF presented as percentage compared to the initial T1) were used as pharmacodynamic endpoints, and the Greco and Minto models were used as surface interaction models. Results The interaction term α of the Greco model for TOF ratio and T1% measurements showed synergism with values of 0.977 and 1.12, respectively. Application of the Minto model resulted in U50 (θ) values (normalized unit of concentration that produces 50% of the maximal effect in the 0 < θ < 1 region) less than 1 for both TOF ratio and T1% measurements, indicating that rocuronium and cisatracurium exhibit synergism. Conclusions Response surface modeling of the interaction between rocuronium and cisatracurium, based on considerations of their effects on muscle relaxation as measured by TOF ratio and T1%, indicated that the two drugs show considerable synergism.

Comparisons of recursive partitioning analysis and conventional methods for selection of uncuffed endotracheal tubes for pediatric patients.

Numerous studies have investigated the best method of selecting the appropriate size of endotracheal tube (ETT) for children. However, none of the methods or formulae for selection of ETT size have shown better prediction over another, and they have required complex formulae calculation or even use of cumbersome equipment. Recursive partitioning analysis creates a decision tree that is more likely to enable clearer and easier visualization of decision charts compared to other data mining methods.

THE EFFECTS OF PENTOBARBITAL AND ISOFLURANE ON CONDITIONED LEARNING AFTER TRANSIENT GLOBAL CEREBRAL ISCHEMIA IN RABBITS

Background The acquisition of a conditioned eyeblink response has been used extensively to study the neurologic substrates of learning and memory. We examined the effects of the anesthetics isoflurane and pentobarbital, or hypothermia (30°C), on the ability of rabbits to acquire an eyeblink conditioned response after 6.5 min of cerebral ischemia. Methods New Zealand white rabbits (n = 48) were randomly assigned to sham, normothermic, hypothermic, isoflurane, or pentobarbital groups. In the normothermic, hypothermic, isoflurane, and pentobarbital groups, 6.5 min of global cerebral ischemia was produced. In animals randomized to the isoflurane and pentobarbital groups, a pattern of burst suppression was achieved on the electroencephalogram before the start of the ischemic episode. Animals in the hypothermia group were cooled to 30°C before ischemia. Seven days after ischemia, eyeblink training was started using an audible tone presented for 100 ms as the conditioned stimulus. The unconditioned stimulus was an air puff directed at the cornea. The delay between the end of conditioned stimulus and the start of the unconditioned stimulus (the trace interval) was 300 ms in duration. A conditioned response was defined as an eyeblink that was initiated during the trace interval. Eighty trials per day and 15 days of training were delivered. Results Neurologic deficits were greatest in the normothermia group, and these animals also had fewer conditioned responses than those in the sham, hypothermia, or pentobarbital groups. Animals in the isoflurane group had an intermediate number of conditioned responses that was not significantly different from the normothermia group. Conclusions This study demonstrates that a brief episode of cerebral ischemia results in the impairment of associative learning. Hypothermia and burst-suppressive doses of pentobarbital were able to improve neurobehavioral outcome as measured by ability to acquire a trace conditioned response.