Takeshi Oguchi

Ephedrine, but not phenylephrine, increases bispectral index values during combined general and epidural anesthesia.

Ephedrine and phenylephrine are used to treat hypotension during combined general and epidural anesthesia, and they may change anesthetic depth. In the current study, we evaluated the effects of ephedrine versus phenylephrine on bispectral index (BIS) during combined general and epidural anesthesia. After injection of ropivacaine through the epidural catheter, general anesthesia was induced with propofol and vecuronium, and was maintained with 0.75% sevoflurane. Approximately 10 min after the intubation, BIS was recorded as a baseline value. Patients with decreases in arterial blood pressure <30% of the preanesthetic values were defined as control group (n = 9). Patients who had to be treated for larger decreases in arterial blood pressure were randomly assigned to receive ephedrine 0.1 mg/kg (n = 17) or phenylephrine 2 &mgr;g/kg (n = 17). BIS values were recorded at 1-min intervals for 10 min. BIS in the ephedrine group was significantly larger from 7 to 10 min than that in the control and phenylephrine groups (P < 0.05). Seven patients in the ephedrine group had BIS >60, whereas no patient in the control and phenylephrine groups had BIS >60 (P < 0.005). Ephedrine, but not phenylephrine, increased BIS during general anesthesia combined with epidural anesthesia.

Hydroxyl radical formation during inhalation anesthesia in the reperfused working rat heart

PurposeTo determine whether isoflurane, sevoflurane and halothane influenced hydroxyl radical production in the ischemic rat heart.MethodsTwenty-four male Wistar rats were divided into four groups; control (C), isoflurane 1.4% (I), sevoflurane 2.5% (S) and halothane 1% (H). The hearts were perfused with modified Krebs-Henseleit bicarbonate buffer by a working heart model for 10 min. Then, whole heart ischemia was induced by severely restricting coronary perfusion for 15 min. Reperfusion of the hearts after this ischemic period lasted for 20 min. The coronary effluent was collected before and during ischemia and at 1,5,10,20 min after reperfusion. At the end of reperfusion, hearts were removed and prepared for measurement. Hydroxyl radicals were identified by their reaction with salicylic acid to yield dihydroxybenzoic acids (DHBAs).ResultsBefore and after ischemia, there were no differences in coronary flow and heart rate among the four groups, but cardiac output and LV dP/dt maximum in the anesthetic groups were lower than in the control group. Hydroxyl radical products in the heart were significantly lower in the I group than the other groups (e.g. C vs I, 278.1 ± 24.3 vs 219.3 ± 14.4 μM· g−1,P < 0.05). The concentrations of DHBAs in the coronary effluent at some points in the I and H groups were less than in the C and S groups.ConclusionThese results indicate that isoflurane and halothane (to a lesser extent), reduce hydroxyl radical production in the ischémie heart, but sevoflurane does not.RésuméObjectifDéterminer si l’isoflurane, le sevoflurane et l’halothane ont influencé la production de radical hydroxyle dans des coeurs de rats ischémiques.MéthodeVingt-quatre rats mâles Wistar ont été répartis en quatre groupes: témoin (T), isoflurane 1,4 % (I), sevoflurane 2,5 % (S) et halothane I% (H). Les coeurs ont été perfuses avec une solution tampon modifiée de bicarbonate Krebs-Henseleit selon un modèle de travail cardiaque pendant 10 min. Ensuite, une ischémie cardiaque totale a été induite en limitant la perfusion coronaire de façon importante pendant 15 min. À la suite de quoi, la reperfusion a duré 20 min. Leffluent coronarien a été recueilli avant et pendant l’ischémie et à 1,5,10,20 min après la reperfusion. À la fin de la reperfusion, les coeurs ont été retirés et préparés pour l’étude. Les radicaux hydroxyles ont été identifiés par leur réaction avec l’acide salicylique pour produire des acides dihydroxybenzoïques (ADHB).RésultatsAvant et après l’ischémie, il n’y avait pas de différence de flux coronarien et de fréquence cardiaque intergroupe, mais le débit cardiaque et le dp/dt maximal du VG dans les groupes I, S et H étaient plus faibles que dans le groupe T. La production de radical hydroxyle dans le coeur était moins importante dans le groupe I que dans les autres groupes (par ex. C vs I, 278,1 ± 24,3 vs 219,3 ± 14,4 μM·g−1,P < 0,05). Les concentrations d’ADHB de l’effluent dans les groupes I et H ont été, à quelques reprises, plus faibles que dans les groupes C et S.ConclusionL’isoflurane et l’halothane (à un moindre degré) réduisent la production de radical hydroxyle dans le coeur ischémique, contrairement au sévoflurane.

Is pentobarbital appropriate for basal anesthesia in the working rat heart model

In the present study we have examined the effects of the general anesthetic agents for the excision of the heart on the hemodynamic function of the ischemic perfused heart. Animals were divided into three groups. In one group rats were anesthetized with sodium pentobarbital intraperitoneally. Animals of the second and third groups were anesthetized with inhalation anesthetics, sevoflurane and isoflurane, respectively. The hearts were then rapidly excised and perfused by a working heart model. After control perfusion, whole-heart ischemia was induced by one-way aortic valve for 15 min followed by reperfusion for 30 min. During preischemic control period, cardiac output (CO) and left ventricular dP/dT maximum (LV dP/dT max) in the isoflurane group were significantly higher than those in the pentobarbital group. During reperfusion, CO and LV dP/dT max in the isoflurane and sevoflurane groups recovered more rapidly than those in the pentobarbital group. Although there were no significant differences in myocardial ATP and glycogen levels among the groups, myocardial lactate in the pentobarbital group was significantly higher than those in the sevoflurane and isoflurane groups. These results suggest that intraperitoneal pentobarbital anesthesia, administered prior to heart excision, may affect the performance of the ischemic perfused heart thereafter. Therefore, we would suggest that isolation of hearts by means of inhalation anesthesia is better than by means of pentobarbital in the working rat heart.

Isoflurane and sevoflurane during reperfusion prevent recovery from ischaemia in mitochondrial KATP channel blocker pretreated hearts.

Background and objective: Inhalation anaesthetics given only during post‐ischaemic reperfusion have some protective effect against reperfusion injury in the heart. Adenosine triphosphate‐regulated mitochondrial potassium channels have been shown to be an important mediator of cardioprotection. Thus, we investigated whether 5‐hydroxydecanoate, a putative mitochondrial potassium channel blocker, prevents the cardioprotective effect of volatile anaesthetics. Methods: Forty rats were randomly allocated to four groups of equal size: control group, 5‐hydroxydecanoate group, 5‐hydroxydecanoate + sevoflurane group and 5‐hydroxydecanoate + isoflurane group. Seven minutes after the start of perfusion, normal saline (control group) or 5‐hydroxydecanoate (the other groups) was administered. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min. One minute before the end of the ischaemic period, 2.7% sevoflurane or 1.4% isoflurane were administered in the 5‐hydroxydecanoate + sevoflurane or 5‐hydroxydecanoate + isoflurane groups respectively. The heart was reperfused for 10 min. Results: Adenosine triphosphate content at the end of reperfusion in the 5‐hydroxydecanoate + sevoflurane group was significantly lower (P < 0.05) than those in the control and the 5‐hydroxydecanoate + isoflurane groups (19.9 ± 8.7, 28.1 ± 3.4 and 30.4 ± 2.3 μmol g−1, respectively). In addition, the combination of inhalation anaesthetics and 5‐hydroxydecanoate decreased the ratios of recovered hearts from ischaemia (5‐hydroxydecanoate + sevoflurane group: 40%, 5‐hydroxydecanoate + isoflurane group 50%). Conclusion: 5‐hydroxydecanoate alone caused no significant changes in haemodynamics and myocardial metabolism. However, the combination of 5‐hydroxydecanoate and volatile anaesthetics impaired the recovery from ischaemia. Although animal data cannot be extrapolated to human beings, we suggest that more attention be paid to patients on sulphonylurea drugs, which inhibit potassium channels, when they are anaesthetized with volatile anaesthetics.

Comparative effects of ringer's acetate and lactate solutions on intraoperative central and peripheral temperatures

STUDY OBJECTIVES To compare the effects of Ringers lactate (LR) and Ringers acetate (AR) solutions on core body and peripheral temperatures during isoflurane or sevoflurane anesthesia. DESIGN Prospective, randomized study. SETTING Operating rooms of a university hospital. PATIENTS 60 ASA physical status I and II patients undergoing general surgery. INTERVENTIONS Following induction with 5 mg/kg of thiamylal and 0.1 mg/kg of vecuronium, patients were randomly assigned to one of four groups (15 patients per group). They received inhalation anesthetics (66% nitrous oxide [N2O] and 1.0% to 2.0% isoflurane or 1.3% to 2.6% sevoflurane) and LR or AR. MEASUREMENTS AND MAIN RESULTS Tympanic membrane (central) temperatures, forearm temperatures, and fingertip temperatures were recorded during surgery every 30 minutes. Tympanic membrane temperatures in the patients given AR were significantly higher than those given LR during isoflurane anesthesia 5 and 30 minutes after induction of anesthesia. However, this was not the case for sevoflurane anesthesia. There were no significant differences in forearm and fingertip temperatures or fingertip bloodflow among the four groups. CONCLUSION There was no significant difference between AR and LR in the preservation of heat during either sevoflurane or isoflurane anesthesia. However, AR may be superior to LR for maintaining central temperature during the early period of isoflurane anesthesia.

The shivering threshold in rabbits with JM-1232(-), a new benzodiazepine receptor agonist.

BACKGROUND: JM-1232(−) is a novel isoindoline derivative which shows sedative and hypnotic activities through the benzodiazepine site of &ggr;-aminobutyric acid type A (GABAA) receptors. Typical doses of midazolam, another GABAA receptor agonist, slightly reduce the shivering threshold in humans. We thus determined the extent to which JM-1232(−) decreases the shivering threshold. METHODS: Eighteen rabbits, lightly anesthetized with isoflurane 0.2 minimum alveolar anesthetic concentration (MAC), were randomly assigned to infusions of 1) saline (control), 2) 0.01 mg · kg−1 · min−1 JM-1232(−), or 3) 0.1 mg · kg−1 · min−1 JM-1232(−). Body temperature was reduced at a rate of 2-3°C/h by perfusing water at 10°C though a U-shaped plastic tube positioned in the colon. Cooling continued until shivering was observed by an investigator blinded to treatment, or until core temperature reached 34°C. Core temperatures were recorded from the distal esophagus, and core temperature at the onset of shivering defined the threshold. Data were analyzed by one-way analysis of variance with Student-Newman-Keuls tests. Results are presented as means ± sd; P < 0.05 was considered statistically significant. RESULTS: The rabbits given a saline infusion shivered at 36.5 ± 0.3°C. Five of the six rabbits given JM-1232(−) at a rate of 0.01 mg · kg−1 · min−1 shivered at 35.7 ± 0.8°C, and one of these rabbits failed to shiver at 34.0°C. None of the rabbits given JM-1232(−) at a rate of 0.1 mg · kg−1 · min−1 shivered before reaching the 34.0°C cutoff temperature. CONCLUSION: A low dose of JM-1232(−) reduced the shivering threshold in rabbits approximately 0.8°C which is similar to the effects in humans given premedication doses of midazolam. In contrast, a 10-fold larger dose reduced the threshold more than 2.5°C. This is a substantial decrement and might facilitate induction of therapeutic hypothermia.

The effects of clonidine premedication on the blood pressure and tachycardiac responses to ephedrine in elderly and young patients during propofol anesthesia

UNLABELLED We studied the pressor and tachycardiac responses to ephedrine in elderly and young patients given either clonidine or midazolam during propofol anesthesia. In the first experiment, elderly (>60 yr) and young (20-45 yr) patients were randomly allocated to one of four groups according to age and premedicated regimens (n = 16 each; elderly-clonidine [EC], elderly-midazolam [EM], young-clonidine [YC], and young-midazolam [YM]). Under propofol anesthesia, ephedrine was injected, and hemodynamic measurements were made. In the second experiment, with clonidine premedication, elderly patients (n = 16) were given a reduced dose of propofol (EC-LP) and young patients (n = 16) were given an increased dose of propofol (YC-HP). Ephedrine was injected, and he- modynamic measurements were performed. The in-creases in mean blood pressure and heart rate were larger in the EC group than in the EM, YM, and EC-LP groups (P < 0.05). In the YC-HP group, the pressor response to ephedrine tended to be augmented as compared with the YC group but was not statistically significant. These results suggest that clonidine premedication augmented the pressor and tachycardiac responses to ephedrine, especially in elderly patients during a standard dose of propofol anesthesia, and that clonidine, age, and propofol could be involved in the augmentation of the blood pressure and tachycardiac responses to ephedrine. IMPLICATIONS Clonidine premedication augments the pressor and tachycardiac responses to ephedrine in elderly patients during standard or large doses of propofol anesthesia but does not augment during small doses of propofol anesthesia. Clonidine, age, and propofol could be involved in the augmentation of the pressor and tachycardiac responses to ephedrine.

Effects of sevoflurane on myocardial metabolism during postischemic reperfusion in the rat

In experiments on isolated rat heart lung preparation, the effects of sevoflurane on myocardial metabolism during postischemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate and glycogen. Hearts were perfused for 10 min initially and made globally ischemic for 8 min. Afterwards, they were reperfused for 12 min. Sevoflurane was administered from 5 min after the start of perfusion to the end of reperfusion. There was no significant difference in myocardial lactate levels between the sevoflurane (S) and control groups. However, the myocardial ATP level in Group S was significantly higher than that in control (17.45±1.51 vs 15.50±0.87:P<0.01). The administration of sevoflurane to the isolated rat heart during pre- and post-ischemia enhanced metabolic recovery in the postischemic state.

Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart

Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins) received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins) received 0.5 U/L insulin during the reperfusion period only. The control group (Control) was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max)) was recorded continuously. Measurements of TNF-α and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max) in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-α levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-α suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.

Baroreflex sensitivity and hemodynamic changes in elderly and young patients during propofol anesthesia

young patients, aged 20–40 years (group Y) scheduled for elective surgery under general anesthesia participated in the present study. Patients with respiratory or cardiovascular disease, diabetes mellitus, or autonomic disorders, as well as patients receiving medication that affects cardiovascular function, were excluded. Premedication consisted of midazolam 0.05 mg·kg 1 administered intramuscularly 30min before anesthesia. Monitors were placed to measure, noninvasively, blood pressure, continuous electrocardiography, and pulse oximetry. A venous catheter was inserted, and acetated Ringer’s solution was infused at a rate of 10ml·kg 1·h 1. After measurements of blood pressure and heart rate, all patients were anesthetized with a bolus propofol injection (1.5 mg·kg 1), followed by continuous intravenous infusion (10 mg·kg 1·h 1). Vecuronium (0.15 mg·kg 1) was given, and tracheal intubation was performed. Ten min after intubation, blood pressure and heart rate were re-evaluated. Then phenylephrine (2 μg·kg 1) was injected. Blood pressure was measured by continuous mode, and heart rate was measured continuously for 10 min after the injection. Values for maximum increase in mean arterial blood pressure (∆MAP) and maximum reflex decrease in heart rate (∆HR) in response to phenylephrine-induced hypertension were obtained. The BRS was assessed as the ratio of ∆HR to ∆MAP (∆HR/∆MAP). Patients’ age, height, weight, and changes in blood pressure, changes in heart rate, and BRS were compared using unpaired t-test. Propofol-mediated changes in blood pressure and HR were analyzed by paired ttest. A P value less than 0.05 was considered statistically significant.