Yoshitami Kadota

The effects of sevoflurane anesthesia on insulin secretion and glucose metabolism in pigs.

We investigated the effects of two different concentrations of sevoflurane, 0.4 minimum alveolar anesthetic concentration (MAC) and 1.0 MAC, on insulin secretion before, during, and after sevoflurane anesthesia using three successive intravenous glucose tolerance tests (IVGTT) in pigs with indwelling catheters. We also investigated changes in the levels of plasma glucose, catecholamines (epinephrine [E], norepinephrine [NE]), and cortisol (Cor). The pigs were grouped as awake, 0.4 MAC, or 1.0 MAC. Sevoflurane decreased the ratio of insulin/glucose (INS/GLU) in the basal condition (P < 0.05 awake versus 1.0 MAC) and during IVGTT (P < 0.01 awake versus 1.0 MAC and 0.4 MAC). These decreases were quickly reversible (control levels were regained within 2 h of the end of anesthesia), were probably dose-related, appeared not to be mediated by E, NE, or Cor. In addition, the INS/GLU ratio 2.5-4 h after the end of anesthesia was significantly higher in the anesthetized groups than in the awake group. We conclude that sevoflurane anesthesia has a rapidly reversible inhibitory effect on basal and glucose-stimulated insulin secretion, as do other inhaled anesthetics, and might induce insulin resistance. (Anesth Analg 1997;84:1359-65)

Comparison between sevoflurane and isoflurane anesthesia in pig hepatic ischemia-reperfusion injury

AbstractPurpose. Sevoflurane and isoflurane have been reported to exert protective effects against ischemia-reperfusion injury (IRI) in various organs. To compare the effect of sevoflurane anesthesia on liver IRI with that of isoflurane anesthesia, we performed the present study in pigs. Methods. Nineteen pigs were assigned to either the sevoflurane (n = 9) or the isoflurane group (n = 10). Hepatic warm ischemia was produced by 30-min hepatic artery and portal vein clamping beginning 90 min after the start of the inhalation anesthesia; this was followed by a 240-min reperfusion. To extend our evaluation, we evaluated the degree of IRI using various parameters (plasma α-glutathione-S-transferase [α-GST], lipid peroxide, and lactate concentrations), in addition to the conventionally used liver damage markers. Results. The lactate level was significantly higher under isoflurane than under sevoflurane at 120 min after reperfusion (4.0 ± 0.4 mmol·l−1vs 2.5 ± 0.3 mmol·l−1; P < 0.05). How-ever, this difference had disappeared after 240 min of reperfusion. No significant differences between the two groups were observed in values for α-GST, lipid peroxides, aspartate aminotransferase, alanine aminotransferase, or lactic dehydrogenase. Conclusion. The extent of the hepatic IRI seen under sevoflurane anesthesia in pigs did not differ significantly from that seen under isoflurane, as judged from measurements of a number of parameters over a 240-min reperfusion period.

Propofol Displays No Protective Effect Against Hypoxia/ Reoxygenation Injury in Rat Liver Slices

Using precision-cut liver slices (20–25 mg wet weight) from male Wistar rats, we examined whether clinically relevant propofol concentrations have hepatoprotective or -toxic effects during hypoxia/reoxygenation. Slices were preincubated for 2 h in sealed roller vials (three slices per vial) containing Waymouth’s medium (37°C; 95% oxygen/5% CO2). Then, propofol or Intralipid was added to create four different groups (control, Intralipid, small-concentration propofol [0.5–1.5 &mgr;g/mL], and large-concentration propofol [2.0–6.0 &mgr;g/mL]). Thereafter, each group was incubated for 4 h under 95% oxygen/5% CO2 (no hypoxia) or for 2 h under 100% nitrogen plus 2 h under 95% oxygen/5% CO2 (hypoxia/reoxygenation). Slice viability and hypoxia/reoxygenation injury were assessed at 2, 3, and 4 h after incubation began by using the slice intracellular K+ concentration, energy status (adenosine triphosphate content, total adenine nucleotides content, and energy charge), and liver enzyme leakage (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase). Propofol and Intralipid caused a significant delay in energy charge recovery in comparison with the control. There were no significant differences between the propofol groups and the other two groups in intracellular K+ content or liver enzyme leakage. Propofol had no hepatotoxic effect under no-hypoxia conditions in rat liver slices, nor did it have a protective effect against hypoxia/reoxygenation-induced hepatic injury.

Renal function after sevoflurane or enflurane anesthesia in the Fischer 344 rat.

Sevoflurane is metabolized to inorganic fluoride, a potential nephrotoxin. To evaluate the nephrotoxic potential of sevoflurane, 1-yr-old male Fischer 344 rats were anesthetized with 10 minimal alveolar anesthetic concentration (MAC) h sevoflurane or enflurane with or without pretreatment with biotransformation-enhancing agents. Peak serum fluoride levels reached 35 μM with sevoflurane anesthesia after pretreatment with Phenobarbital and 40 μM after enflurane anesthesia after pretreatment with isoniazid. One day after anesthesia, sevoflurane-anesthetized rats concentrated urine normally in response to subcutaneous administration of 1-deamino-8-D-arginine vasopressin and exhibited no increase in urinary excretion of N-acetyl β-glucosaminidase. Isoniazid-treated, enflurane anesthetized rats developed a 31% reduction in maximal urinary concentrating ability and a 3.5-fold increase in excretion of N-acetyl-β-glucosaminidase. Sevoflurane produced no evidence of fluoride-induced nephrotoxicity in noninduced or enzyme-induced rats. Under similar conditions, enflurane produced laboratory evidence of nephrotoxicity.

Subcutaneous Administration of Desmopressin as a Test of Maximal Urinary Concentrating Ability in the Fischer 344 Rat

Decreased maximal urinary concentrating ability after administration of vasopressin analogs is a sensitive indicator of some forms of nephrotoxicity. To evaluate the potential of subcutaneous injection of 1 -deamino-8-D-arginine vasopressin (desmopressin) as a provocative agent in testing maximal urinary concentrating ability, rats were administered desmopressin acetate subcutaneously and urine osmolality was measured. At all dosages used (3–300 ng/kg), urinary osmo-lality increased for the first 4 h after desmopressin administration. At dosages > 100 ng/kg, osmolality remained elevated for 8 h. The utility of desmopressin administration in detecting urinary concentrating defects was validated by pre-treating rats with sodium fluoride and measuring maximal urine concentrating ability after administration of 100 ng/kg desmopressin. Administration of 100 or 200 μmol sodium fluoride (NaF) intraperitoneally daily for 3 days, resulted in 55 and 60% decrease, respectively, in maximal urinary concentrating abili...

Changes in erythrocyte membrane fluidity by endotoxin in rats.

The effect of endotoxin on fluidity and lipid composition of the erythrocyte membrane was studied in rats following the intraperitoneal administration of endotoxin (30 mg-kg−1 body weight). Erythrocyte membrane fluidity measured with 16-stearic acid spin label (16-SAL) was significantly decreased in the endotoxin-treated rats as compared with control. A decrease of lysophosphatidylcholine in the membrane lipid was evident in the endotoxin-treated rats. The cholesterol to phospholipid molar ratios and other phospholipid fractions did not differ significantly in the two groups.The levels of plasmaβ-glucuronidase activity and lipoperoxide were significantly increased in the endotoxin-treated rats when compared to controls. There were significant correlations between the parameter of 16-SAL in erythrocytes and plasmaβ-glucuronidase activities or lipoperoxide from both endotoxin-treated and control groups,P<0.005 orP<0.02 respectively.In conclusion endotoxin decreased rat erythrocyte membrane fluidityin vivo. Since membrane fluidity is closely related to the vital functions of the membranes, the change described could be related to the abnormality of cell membrane functions in endotoxin shock state.

Propofol in a patient at risk for malignant hyperthermia : report of a case

Malignant hyperthermia (MH) is a syndrome triggered by volatile inhalation anesthetics and/or succinylcholine. The symptoms are the result of hypermetabolism in skeletal muscle. Although the mortality rate has now dropped to less than 5%, MH is still one of the most serious complications of general anesthesia [1]. Although several reports have suggested that propofol is safe to use in patients who have a history of MH [2,3] or who are considered to be susceptible to MH [4-6] , there have been no studies of changes in serum creatine kinase (CK), serum myoglobin (Mb), and urine Mb during and after propofol anesthesia. We report a case of the successful use of propofol in a patient with a history of MH.

Difficulty in the removal of both nasogastric and endotracheal tubes : report of a case

A 50-year-old man was scheduled to undergo esophagectomy after a diagnosis of esophageal cancer. Anesthesia was induced with thiamylal, followed by vecuronium to obtain muscle relaxation, and was maintained with isoflurane and nitrous oxide in oxygen. Oral intubation of a double-lumen endotracheal tube was performed with slight difficulty and we then tried to insert a nasogastric tube from his right nostril to the stomach. At the end of the operation, the doublelumen endotracheal tube was extubated and a new single-lumen endotracheal tube was reintubated through the left nostril. When we tried to pull out the gastric tube from his right nostril, we had difficulty in removing it. In addition, we were unable to remove the endotracheal tube. Upon X-ray examination and fiberscopic analysis, we discovered that the nasogastric tube was wound around the endotracheal tube in a loop in the upper pharynx (Fig. 1). With the aid of a