Effects of ulinastatin (urinary trypsin inhibitor) on ATP, intracellular pH, and intracellular sodium transients during ischemia and reperfusion in the rat kidney in vivo.

PURPOSE: To investigate the effects of ulinastatin on renal ischemia-reperfusion injury, we monitored the dynamic changes in ATP, intracellular pH (pHi), and intracellular sodium (Nai) in rats in vivo. METHODS: Renal ischemia was induced by clamping the abdominal aorta for 30 min followed by reperfusion for 60 min. Ulinastatin, 50,000 U.kg(-1) (UTI group), or normal saline (NS group) was infused for 30 min before ischemia. (31)P- and double quantum (23)Na-NMR were used to monitor ATP, pHi, and Nai. RESULTS: During ischemia, ATP was rapidly depleted and Nai increased to the same extent in both groups. After 60 min reperfusion, Nai in the NS group was almost restored to the preischemic baseline level (117.2 +/- 7.4% of the baseline value), but the recovery of ATP was incomplete (60.9 +/- 7.7%). The recovery of Nai in the UTI group began earlier than in the NS group with better recovery of ATP. The pHi values showed severe acidosis in the NS group compared with the UTI group during ischemia and reperfusion. As for ultrastructural findings, after 60 min reperfusion, the mitochondria were less swollen and less disorganized with respect to the membrane and the cristae in the UTI group. CONCLUSION: The transcellular sodium gradient is restored before the ATP level is normalized during postischemic reperfusion. Ulinastatin might protect mitochondrial conformation during ischemia, and facilitate functional recovery of the ionic pump after reperfusion.

Serum glutathione S-transferase alpha as a measure of hepatocellular function following prolonged anaesthesia with sevoflurane and halothane in paediatric patients.

We studied the effects of prolonged anaesthesia (4.3-7.7 h) with sevoflurane and halothane on hepatic function in 14 paediatric patients. Hepatic function was assessed using serum concentrations of liver-specific glutathione S-transferase alpha (GSTA) before and 0, 3 and 15 h after the end of anaesthesia. A transient significant increase in GSTA over baseline was observed in the sevoflurane group, but not in the halothane group, and the difference between the groups was not significant. These data suggest that, although statistically insignificant, the use of sevoflurane for prolonged anaesthesia in paediatric patients is more likely than halothane to be involved in damage to hepatic function.

Dose-dependent effects of propofol on renal sympathetic nerve activity, blood pressure and heart rate in urethane-anesthetized rabbits.

To evaluate the role of the autonomic nervous system in hemodynamic changes after propofol bolus injection, we used direct recordings of renal sympathetic nerve activity to examine the dose-dependent effects of propofol (2.5, 5, 10, and 20 mg/kg) on heart rate, mean blood pressure and renal sympathetic nerve activity in urethane-anesthetized rabbits. The animals were divided into four groups: animals with an intact neuraxis (intact group), cervical vagal nerve-sectioned animals (vagotomy group), carotid sinus and aortic-nerve sectioned animals (SAD group), and animals with SAD plus vagotomy (SADV group). Heart rate did not change significantly even after administration of 2.5 and 5 mg/kg but decreased markedly on 20 mg/kg injection in all groups. The intact and vagotomy groups had augmented renal sympathetic nerve activity with insignificant changes in mean blood pressure after 5 mg/kg injection of the agent. Insignificant changes of renal sympathetic nerve activity but a remarkable decrease of mean blood pressure appeared after 10 mg/kg propofol. Sustained hypotension in parallel with a profound depression of renal sympathetic nerve activity developed at the dose of 20 mg/kg. In SAD and SADV groups, however, dose-dependent depressions of renal sympathetic nerve activity were accompanied by decreases of mean blood pressure. These results suggest the following: (1) propofol-induced hypotensive effects are probably produced by the central-mediated sympathetic depression. (2) The baroreceptor reflex may be preserved at the lower dose of the agent. (3) Heart rate does not change significantly unless a large dose of propofol is used. The difference in effects on heart rate and on mean blood pressure may denote a greater inhibition of sympathetic vascular outflow than of the cardiac sympathetic outflow regulating cardiac rate and contractility. This hypothesis needs further clarification.

Effects of induced hypothermia on renal sympathetic nerve activity and baroreceptor reflex in urethane-anesthetized rabbits.

OBJECTIVE: To evaluate the role of the autonomic nervous system in hemodynamic changes during induced hypothermia. DESIGN: Prospective, randomized animal study. SETTING: An animal research laboratory in a medical university. SUBJECTS: A total of 29 anesthetized rabbits. INTERVENTIONS: Animals were anesthetized by intraperitoneal urethane. After tracheostomy and administration of gallamine, respiration was maintained by mechanical ventilatory support. The animals were divided into five groups (one control and the four experimental groups); animals were treated with an intact neuraxis and normothermia (control group), animals with an intact neuraxis (intact group), cervical vagotomized animals (vagotomy group), the carotid sinus and aortic nerves denervated animals (SAD group), and animals with SAD plus vagotomy (SADV group). The left renal sympathetic nerves were exposed by a retroperitoneal approach. MEASUREMENTS AND MAIN RESULTS: We examined the effects of surface cooling on HR, mean arterial pressure, central venous pressure, and renal sympathetic nerve activity (RSNA) in the animals. Changes of baroreflex sensitivity and plasma catecholamines were also measured simultaneously. Surface cooling caused progressive and profound decreases in HR in all experimental groups. In all groups, RSNAs increased at the early phase, which were followed by return to the precooling level. CONCLUSIONS: Hemodynamics and RSNA during induced hypothermia are regulated by mechanisms other than the baroreceptor reflex system, possibly the dermal cold receptors. Suppression of the baroreflex occurred on HR but not on RSNA during hypothermia, which may indicate direct effects of hypothermia on the heart. RSNA responses may be activated earlier than systemic catecholamine responses during induced hypothermia.

[Mass-casualties due to chemicals].

Mass casualties due to chemicals and chemical weapons are typical man-made disasters. As they occur without connection to time, place, and occasion, an adequate crisis control system is needed. Although the possibility that chemical weapons will be used in terrorism, as in Matsumoto and the Tokyo sarin attack, has recently increased, mass casualities due to the combustion and leakage of toxic chemicals in the chemical industry and traffic accidents during the transport of chemicals are more likely since about 5000 new chemical substances are synthesized every year.

Intra-axonal continuous measurement of lidocaine concentration and pH in squid giant axon.

PURPOSE: To measure the dynamic penetration process of lidocaine, lidocaine concentration (Ci) and pH (pHi) in squid giant axon, and to determine the times and Ci of disappearance and reappearance of action potentials (AP). METHODS: Lidocaine solutions adjusted to four different pHs (pH = 5.5, 6.8, 7.8 and 9.0) were externally administered to the axon and Ci and pHi were measured using lidocaine and pH microsensors. The times and Ci when the AP just disappeared and reappeared were recorded. In addition, for comparison with Ci, the lidocaine content in the whole axon (Cw) was measured with high-performance liquid chromatography (HPLC). RESULTS: The Ci (charged plus uncharged) was 1.5 times greater than the uncharged form of administered lidocaine. The changes in pHi depended on the increase in Ci. The AP disappeared only after administration of high pH lidocaine solutions (pH = 7.8, 9.0) and reappeared by washing out the solution in the chamber. Nerve block occurred more rapidly at pH 9.0 than at pH 7.8, and the time after washing out the lidocaine was longer at pH 9.0 than at pH 7.8. The mean Ci and charged lidocaine concentration in the axoplasm, when the AP disappeared or reappeared, were lower at pH 9.0 than at pH 7.8 (P < 0.05). CONCLUSION: Uncharged lidocaine penetrates the axon membrane to the axoplasm where it changes to the charged form and is concentrated in the axon membrane and axoplasm. External application of uncharged lidocaine plays a role in modulating nerve conduction.

Repetitive post-training exposure to enflurane modifies spatial memory in mice.

BACKGROUND: Previously the authors found that a single post-training exposure to enflurane or isoflurane, but not halothane, enhanced memory storage in an active avoidance task, which is a behavior with underlying mechanisms that are poorly understood and still debated. In contrast, spatial tasks are known to depend on hippocampal functions. This study investigated the effects of repetitive post-training exposure to enflurane on spatial memory in mice. METHODS: Using an eight-arm radial maze, 80 mice were trained to eat a pellet placed on the end of each of the eight arms. Training occurred on four consecutive days with one trial per day. The number of errors in the first eight choices was recorded to determine performances for each day of training. Immediately after each training session, mice in the enflurane group received 1 h exposure to 0.5%, 1%, or 2% enflurane in air through a calibrated vaporizer. The performance ratios (the ratio of errors on each day compared with the first day of the 4 days) in the control and the enflurane groups were compared. RESULTS: The performance ratios (which equals the mean of the error in the fourth day/the error in the first day) in the control, and 0.5%, 1%, and 2% enflurane groups were 0.66, 0.65, and 0.32 (P < 0.01, vs. control), and 0.46 (P < 0.05, vs. control), respectively. CONCLUSIONS: Repetitive post-training exposure to 1% and 2% enflurane significantly enhanced spatial memory in the eight-arm radial maze task. Enflurane enhances consolidation of spatial memory, possibly by affecting hippocampal activity.

Effects of dexmedetomidine, an alpha2-adrenoceptor agonist, on renal sympathetic nerve activity, blood pressure, heart rate and central venous pressure in urethane-anesthetized rabbits.

To clarify the role of the neural blood pressure control system in hemodynamic changes after dexmedetomidine (DXM) administration, we examined the effects of an intravenous injection of DXM (10 microg/kg) on heart rate (HR), mean blood pressure (MBP), central venous pressure (CVP) and renal sympathetic nerve activity (RNA) in urethane-anesthetized rabbits using direct recordings of RNA. The animals were divided into four groups: animals with an intact neuraxis (intact group; n = 12), cervical vagotomized animals (vagotomy group; n = 5), sino-aortic denervated animals (SAD group; n = 5), and animals with SAD plus vagotomy (SADV group; n = 5). An initial HR decrease, which occurred in the intact group, did not occur in the other three groups, suggesting the mediation of the baroreflex. A subsequent HR decrease occurred in the three groups other than the vagotomy group, in which RNA recovered earlier than in the other groups. RNA in the intact group, associated with transient hypertension, was suppressed shortly after the injection. Such an RNA drop was not eliminated even in the SADV group. Despite recovery of RNA, hypotension lasted until the end of experiment in the intact and vagotomy groups. However, sustained depression of RNA associated with lasting hypotension was found in the SAD and SADV groups. CVP in all groups did not change significantly after the injection. These results suggest the following: (1) Initial bradycardia after DXM is mediated via the baroreflex. Subsequently, HR reductions may result mainly from central sympathetic depression. (2) An initial reduction in RNA is not mediated via the baroreceptor reflex, unlike HR responses, but by central sympatho-inhibitory effects. (3) Long-lasting hypotension after DXM is likely to be attributable to its peripheral vascular effects including the stimulation of pre-synaptic alpha2-adrenoceptors, rather than to central sympathetic depression.

The effect of volatile anesthetics on light-induced phosphorylation in spinach chloroplasts.

(1) The light-induced phosphorylation in spinach chloroplast is coupled with proton transfer. (2) We investigated the effect of volatile anesthetics (halothane, enflurane, isoflurane) on the cyclic and/or non-cyclic light-induced phosphorylation. (3) We used potassium ferricyanide as a Hill oxidant for non-cyclic phosphorylation and phenazin-methosulfate as an oxidation-reduction indicator for cyclic phosphorylation. (4) These three anesthetics inhibit the Hill reaction in light induced phosphorylation. The inhibition rate of this reaction generates concave curves with minimum values at 303 K in each of the anesthetics.

Effects of halothane and supporting membrane lipids on the activity of acetylcholinesterase.

1. The activity of acetylcholinesterase in the human erythrocyte membrane was measured with and without halothane. 2. To evaluate the roles of the supporting membrane lipids, the enzyme protein was solubilized from the membrane with a surfactant, Triton X-100. 3. It is confirmed that membrane lipids alter the activation energy of the enzyme bound to the membrane, and strengthen the effects of halothane and Triton X-100 on the enzyme activity by providing a high concentration field of them around the enzyme.

[Efficacy of ring-shape cover in active skin surface warming in neonates--a retrospective comparative study with conventional methods].

UNLABELLED: Prevention of perioperative hypothermia is one of the most essential factor for neonatal anesthesia. Recently the forced-air warming system has been considered the most effective method in preventing perioperative hypothermia in adults, in children, and in infants during maxillofacial operations. However, its use for abdominal or thoracic surgery in neonates has not been examined. In the present study, we studied the effects of the forced-air warmer with a ring-shape cover, and compared this method with the conventional method retrospectively. PATIENTS AND METHODS: Sixteen neonates, 13 for abdominal and 3 for thoracic surgery were anesthetized with oxygen-air (nitrous oxide) sevoflurane (isoflurane or enflurane) in combination with/without fentanyl. They were divided into two groups; one for forced-air warming (F-group), and another for conventional methods (C-group). The patients' mean age, height and weight, the duration of anesthesia, infusion rate (ml.kg-1.hr-1), and urine output did not differ each other. Patients in F-group were placed in the center of the ring-shape cover and received heated air from their surroundings. We did not use any other warming equipment or means except for an artificial nose and a warming mattress. "Medium" heated air (38 degrees C) or unheated, room temperature air were used when necessary. The operating room temperature was kept around 25 degrees C. Patients in the C-group were placed on a warming mattress and under an infrared radiant heater with the room temperature of 30 degrees C. Their extremities were covered with aluminum-foil. Rectal, deep forehead, and deep sole temperatures were monitored throughout anesthesia. RESULTS AND CONCLUSION: In F-group, temperatures were well maintained, while C-group failed to maintain. In F-group, the mean value of base excess at the beginning of the operation was -1.8 mM, but it was restored to normal level without administration of sodium bicarbonate. No complications were found. Thus, compared to conventional methods, the forced-air warming system with a ring-shaped cover is an efficient method for body temperature management in neonatal anesthesia.

Psychomotor performance during initial stage of exposure to halothane, enflurane, isoflurane and sevoflurane in mice.

1. The dose-response relationship during the pre-anaesthetic and pre-equilibrium state of four inhalation anaesthetics (halothane, enflurane, isoflurane and sevoflurane) on fixed-ratio schedule-controlled behaviour was studied in mice. 2. Animals exposed to halothane, enflurane and isoflurane showed a biphasic pattern (i.e. a significant incremental increase in psychomotor responses at low inspired concentrations (0.1-0.4%) and decrements at greater concentrations) in a dose-dependent manner. Mean peak responses (per cent of control) were 132.3 (P < 0.01 vs control), 124.0 (P < 0.05) and 116.7% (P < 0.05) at 0.1% halothane, 0.3% enflurane and 0.2% isoflurane, respectively. 3. Sevoflurane did not increase schedule-controlled behavioural responses at any concentration. 4. The effect of subanaesthetic concentrations of inhalation anaesthetics on psychomotor performance can be evaluated as changes in the response rate in schedule-controlled behaviour.

[Urinary excretion of ulinastatin and NAG after cardiopulmonary bypass].

Although urinary trypsin inhibitor (ulinastatin, UTI) is excreted into urine, its physiological function has not been clarified well. Administration of UTI during surgical procedure was reported to protect renal function from surgical stress. This result suggests participation of UTI excretion in renal tubular function. In this study, the amount of urinary excretion of UTI and that of N-acetyl-beta-D-glucosaminidase (NAG) after cardiopulmonary bypass (CPB) were measured. The urinary UTI excretion increased after surgery and reached the maximum on the third postoperative day. NAG also increased gradually and was three times greater than control on the seventh postoperative day. There was a good correlation between NAG and UTI on the first postoperative day. It is suggested that UTI might correlate with the renal tubular function after CPB.

[Significance of postoperative elevation of urinary ulinastatin after open heart surgery under cardiopulmonary bypass].

To investigate the role of ulinastatin in perioperative stress, we measured the urinary levels of ulinastatin (UTI) in patients subjected to open heart surgery under cardiopulmonary bypass. The UTI levels began to increase on the first postoperative day and reached its maximum level on the third postoperative day. There is a good correlation between the maximum level of urinary UTI and cardiopulmonary bypass time. These results indicate that urinary UTI level can be an indicator of surgical stress.

[Effects of ulinastatin on postoperative renal function in hepatectomized patients with liver cirrhosis].

Posthepatectomy patients with liver cirrhosis have a high incidence of multiple organ failure including renal failure. The depression of urinary ulinastatin (UTI) might be involved in renal derangements in the posthepatectomy patients with liver cirrhosis. We evaluated the relationship between the renal functions and the level of urinary UTI in perioperative period in the posthepatectomy patients with liver cirrhosis, and evaluated whether or not the renal function in the posthepatectomy patients with liver cirrhosis was protected by receiving synthetic UTI, Miraclid. In posthepatectomy patients with liver cirrhosis, the urinary UTI level was 26.3 +/- 13.0 IU. mg x Cr-1 on the first day and renal tubular dysfunction was noticed. On the other hand, in posthepatectomy patients with liver cirrhosis receiving Miràclid administered intravenously during the operation and postoperative three days, the urinary UTI level was 121.2 +/- 85.0 IU. mg x Cr-1 on the first day and renal function was maintained. These results indicate that in posthepatectomy patients with liver cirrhosis, an increase in urinary UTI level observed in response to surgical stress may not occur and this low level of urinary UTI may cause renal dysfunction in the postoperative period. The synthetic UTI, Miraclid, may have beneficial effects reversing the renal derangements resulting from the stress in posthepatectomy patients with liver cirrhosis.

Spontaneous breathing with the use of a laryngeal mask airway in children: comparison of sevoflurane and isoflurane.

We compared respiratory parameters during anaesthesia with sevoflurane and isoflurane through a laryngeal mask airway (LMA). Children were anaesthetized with O2 and air with 2.3% (1MAC) sevoflurane (n = 20) or 1.5% (1MAC) isoflurane (n = 20). After insertion of LMA, patients were allowed to breathe spontaneously and respiratory rate (RR) and PECO2 were measured (presurgery state). After the measurement, anaesthetic concentration was increased to 1.3 MAC (3.0% sevoflurane or 2.0% isoflurane) and surgical stimulation was added. Fifteen min after incision, the measurements were again performed (during surgery). In the sevoflurane group, mean RR and PECO2 were 32 breaths.min-1, and 6.0 kPa (45 mmHg) respectively, before surgery, and 35 breaths.min-1 and 7.0 kPa (52 mmHg) during surgery. In the isoflurane group, mean RR and PECO2 were 32 breaths.min-1 and 6.1 kPa (46 mmHg) respectively, before surgery, and 37 breaths.min-1 and 6.7 kPa (52 mmHg) during surgery. There were no statistical differences between the two anaesthetic groups. Clinical respiratory and cardiovascular parameters during spontaneous breathing with LMA in children are similar during sevoflurane and isoflurane anaesthesia.

Multiple but different genetic factors underlie enflurane and isoflurane requirements studied through backcross analysis in C57BL and ddN mice.

We performed a classic backcross analysis to examine the basic genetic nature of enflurane (ENF) and isoflurane (ISO) anesthetic requirement in two inbred mice strains, C57BL (BL) and ddN. We have previously reported different ENF and ISO anesthetic requirements in these two strains. BL (n = 22) and ddN (n = 26) mice were used as parents and were reciprocally crossed to produce F1 hybrid mice. Each F1 offspring was crossed to its parent to produce backcross siblings (BF1). Anesthetic end point was determined as the loss of righting reflex. Measurement of anesthetic requirement was performed during 8-12 wk after birth. Although ddN mice showed slightly less resistance to ENF and ISO compared with our previous report, they were more resistant than BL mice. Multivariate regression analysis of parents' and F1 hybrids' data revealed that, while maternal factors and factors on autosomes were related to both anesthetics, the factors on the X chromosome were ENF specific. A wide variation in anesthetic requirements among BF1 progeny suggested multifactorial inheritance. The regression equations obtained did not always predict anesthetic requirement in BF1 progeny. These discrepancies may be due to the epistatic interaction of related genes. We conclude that multiple but different genetic factors are involved in determining ENF and ISO anesthetic requirements in BL and ddN mice.

[Changes of urinary ulinastatin and serum CRP after elective surgery for gastric cancer].

Urinary ulinastatin (UTI) is elevated in various conditions, such as renal disease, myocardial infarction, neoplasm, leukemia and normal pregnancy. The purpose of the present study is to measure the change of UTI after surgery for gastric cancer and to compare with other acute phase reactants. Urine samples were collected from 7 surgical patients. UTI level was measured by radioimmunoassay and corrected by urinary level of creatinine. UTI levels began to increase from the first postoperative day and reached the maximum level on the third postoperative day. The pattern of UTI correlated with that of serum CRP levels. Meanwhile, when patient was in inflammatory condition postoperatively, UTI increased further and its pattern correlated with that of serum CRP levels. These results suggest that UTI is an acute phase reactant and a sensitive marker indicating the degree of inflammatory condition after surgery.

[Acute alcoholism after ethanol fixation for ovarian chocolate cyst].

We experienced a case of acute alcoholism after ethanol fixation for ovarian chocolate cyst. A 46 year old female was scheduled for ethanol fixation for ovarian chocolate cyst. Ethanol fixation was performed with 110 ml of 99% ethanol under general anesthesia. Ethanol 70 ml was not removed. After the operation, patient did not emerge from anesthesia within 30 min. Blood alcohol concentration was 232 mg.dl-1. It is important to remove total ethanol used for ethanol fixation in anesthetic management for ethanol fixation for ovarian chocolate cyst.

[Postoperative urinary ulinastatin secretion and renal function in hepatectomized patients with and without liver cirrhosis].

We compared ulinastatin secretion into urine with renal function during postoperative period in three groups, hepatectomized group with liver cirrhosis (LC(+), n = 7), hepatectomized group without liver cirrhosis (LC(-), n = 4) and subtotal gastrectomized group with normal liver function (GR, n = 7). In LC(+) group, N-acetyl-beta-D-glucosaminidase (NAG) increased above normal upper limit throughout the postoperative period. Ulinastatin (UTI) also increased but the increase was not remarkable. In LC(-) group, NAG increase but not significantly compared with the preoperative value. UTI increased from 5.8 +/- 3.0 IU.mg x Cr-1 to 30.8 +/- 16.6 IU.mg x Cr-1 and 39.9 +/- 9.0 IU. mg x Cr-1 on the 1st and 3rd postoperative day respectively. In GR group, there was no change in NAG value. UTI on the 3rd postoperative day increased significantly (from 10.0 +/- 7.7 to 75.4 +/- 39.0 IU.mg x Cr-1). A small urinary secretion of UTI and increased NAG during postoperative period in LC(+) group suggest that UTI might play an important role in postoperative renal dysfunction in patients with liver cirrhosis.