[Evaluation of inhibitory effect of isoflurane on the hypoxic pulmonary vasoconstriction response in dogs].

The effect of isoflurane on hypoxic pulmonary vasoconstriction (HPV) was examined using the separately ventilated left lower lobe lung model in dogs. When the HPV was induced with anoxic gas ventilation of the left lower lobe, the magnitude of HPV inhibition by isoflurane of 2 MAC was predominant, as assessed by the index of pressure-flow curve which is a novel indicator of pulmonary vascular tone in the left lower lobe. However, isoflurane 2 MAC attenuated the HPV by only 16%, as assessed by indices of the changes in left lower lobe blood flow rate and PaO2. This weak HPV inhibition, as shown by the latter parameters, may result from the net effect of isoflurane-induced HPV inhibition and secondary HPV enhancement due to decreases in cardiac output and pulmonary arterial pressure by isoflurane. However, none of the parameters showed inhibition of HPV when the HPV was induced by collapse of the left lower lobe. This discrepancy in the results may be caused by a lack of isoflurane reaching the hypoxic lobe when the HPV is induced with atelectasis. These results show that potency of HPV inhibition with isoflurane depends on the method of induction or evaluation of HPV, and that inhibition of HPV response with isoflurane at clinical concentrations is negligible in an atelectasis-induced HPV, in which no isoflurane is directly reaching the hypoxic lobe.

Effect of sevoflurane on hypoxic pulmonary vasoconstriction in the perfused rabbit lung.

BACKGROUND: In vitro studies have shown that isoflurane, enflurane, and halothane inhibit the hypoxic pulmonary vasoconstriction (HPV) with essentially the same potency. The aim of this study is to compare the effects of sevoflurane and isoflurane on HPV in constant-flow perfused rabbit lungs. METHODS: Constant-flow perfused lungs from Japanese white rabbits were tested. The lungs were divided into three groups: isoflurane alone (n = 6), sevoflurane alone (n = 6), and sevoflurane with ibuprofen pretreatment (n = 6). Baseline HPV responses were measured as the pulmonary arterial pressure increased after changing inspired oxygen concentration from 95% for 15 min to 3% (with 5% CO2) for 5 min without anesthetic administration. Next, three different concentrations of anesthetics were added to the inspired gas for 15 min in random order. The HPV response in the presence of anesthetic was expressed as a percentage of the pressor response in the absence of anesthetics, and dose-response relationships were calculated using the nonlinear least-squares method. RESULTS: Isoflurane and sevoflurane both depressed the HPV response in a dose-related manner. The half-inhibition values (ED50) of HPV with isoflurane and sevoflurane were 0.85 +/- 0.22 MAC and 1.00 +/- 0.12 MAC (mean +/- SD), respectively, and were not statistically different. Ibuprofen pretreatment did not alter ED50 and slope of dose-response curve, although the absolute value of pressor response in the sevoflurane group with ibuprofen pretreatment was greater than that in the sevoflurane alone group at every concentration of sevoflurane. CONCLUSIONS: Sevoflurane inhibits the HPV response in a dose-related manner, and its potency is similar to that of isoflurane in vitro. Cyclooxygenase products do not mediate the inhibition of HPV by sevoflurane.

Effects of sevoflurane and halothane on reperfusion-induced arrhythmia in the isolated rat heart.

The effects of sevoflurane and halothane on reperfusion-induced arrhythmia in the isolated rat heart were examined. Reperfusion-induced ventricular fibrillation (VF) occurred in all rat hearts, and the duration of VF was 151 +/- 11 (mean +/- SEM) seconds in the control group (no anesthetics administered). Sevoflurane changed neither incidence nor duration of VF at 1, 2, and 3 minimum alveolar concentrations (MAC) of anesthetic. Halothane altered neither the incidence nor duration of VF compared with the control group at 1 MAC; however, at 2 and 3 MAC, halothane significantly reduced the incidence and duration of VF (P < 0.05 at 1, 2, and 3 MAC halothane: respective incidences were 100%, 18%, and 55% and respective durations, 82 +/- 27 seconds, 20 +/- 6 seconds, and 13 +/- 9 seconds). In the isolated rat heart, we found that halothane has antiarrhythmic effects against reperfusion-induced arrhythmia at 2 and 3 MAC. Sevoflurane, however, did not have any antiarrhythmic effects against reperfusion-induced arrhythmia at 1, 2, or 3 MAC.

Naloxone and flumazenil fail to antagonize the isoflurane-induced suppression of dorsal horn neurons in cats.

Effects of naloxone and flumazenil on isoflurane activities were examined on dorsal horn neurons in cats. Isoflurane suppressed bradykinin-induced nociceptive responses in transected feline spinal cords. The bradykinin-induced neuronal firing rates were significantly suppressed by 60.0%, 35.3% and 32.2% at 10, 20 and 30 min after isoflurane administration, respectively. The 32.3% suppression on bradykinin-induced neuronal responses at 30 min after isoflurane administration was not reversed 5 min after administration of naloxone (36.4% suppression). The suppressive effects of isoflurane were not reversed by naloxone (0.2 mg.kg(-1), i.v.). Similarly, the benzodiazepine antagonist, flumazenil (0.2 mg.kg(-1), i.v.), did not affect the suppressive effects of isoflurane. Failure of naloxone and flumazenil to reverse the suppressive effects of isoflurane suggests that isoflurane interacts with neither opioid nor benzodiazepine receptors in producing its suppressive action on nociceptive responses in dorsal horn neurons of the feline spinal cord.

[Interaction of midazolam and vecuronium in anesthetized patients].

The interaction between midazolam and vecuronium was investigated in 60 patients during isoflurane-nitrous oxide-oxygen anesthesia. Neuromuscular function was evaluated by recording the single twitch of the abductor pollicis muscle. Anesthesia was induced with thiamylal 4 mg.kg-1 or midazolam 0.2 mg.kg-1 followed by injection of vecuronium 0.1 mg.kg-1. Observed values after midazolam were compared with those observed in patients with thiamylal. the onset time and the duration of action until 25% recovery were similar with both groups. Midazolam caused no significant potentiation of neuromuscular blocking agents in comparison with the control. Therefore, there was no evidence of any interaction between midazolam and vecuronium during isoflurane-nitrous oxide-oxygen anesthesia.

The influence of volatile anesthetics on portwine stain.

To examine the relationship between volatile inhalation anesthetics and the fading of portwine stain (PWS), the study retrospectively investigated the incidence of termination of pulsed dye laser treatment vis-à-vis PWS fade during use of a general inhalation anesthetic in 107 infants and children with facial PWS. The fading of PWS is disadvantageous to the pulsed dye laser treatment. All patients received pulsed dye laser treatment under general anesthesia using one of four kinds of volatile inhalation anesthetics (halothane, enflurane, isoflurane, and sevoflurane). Two hours before the induction of anesthesia, all patients were rectally irrigated. Treatment was discontinued in none of the 44 patients in the halothane group or the 7 patients in the enflurane group; in one of the 29 in the isoflurane group; and in 10 of the 27 patients in the sevoflurane group. The sevoflurane group showed a significantly (P < 0.01) higher incidence of PWS fading. Thus, when using a volatile inhalation anesthetic in combination with pulsed dye laser treatment for PWS, caution should be exercised if sevoflurane is selected, as PWS fading is harmful to the pulsed dye laser.

[Evaluation of halothane induced HPV inhibition with analysis of pressure-flow curve].

We investigated the effect of halothane on the hypoxic pulmonary vasoconstriction using in vivo measurement of the pressure-flow curve of the left lower lobe in the dog. With hypoxic ventilation of the left lower lobe, the pressure-flow curve shifted to the right and the slope of the curve became flatter. Although inhalation of 1 MAC halothane by the left lower lobe during hypoxic ventilation had no effect on the pressure-flow curve configuration, inhalation of 3, 5 MAC made the slope steeper. We analyzed these changes by the distensibility model proposed by W. Mitzner et al, and our data support the hypothesis that hypoxic ventilation decreases the small pulmonary vessels of 1-4 orders and also increases the compliance of the orders of vessel where the constriction has occurred, and halothane antagonizes the HPV response by further increasing the compliance of the constricted vessels. The inhibitory effect of halothane on HPV was weaker in in vivo preparation compared with the effect in in vitro preparation. Some humoral factors in the perfusate could contribute to this effect.

Suppressant effects of midazolam on responses of spinal dorsal horn neurones in rabbits.

Recordings of noxious intra-arterial bradykinin (BK)-induced chemonociceptive and spontaneous activity from 30 single spinal lamina V neurones of the dorsal horns in non-anaesthetized and decerebrated rabbits, were performed with tungsten microelectrodes. Intravenous injection of midazolam (0.2 mg/kg; 7 neurones) depressed BK-induced neural discharges by 55.0 +/- 6.2% (P less than 0.05) and 57.9 +/- 8.4% (P less than 0.05) 5 and 25 min after administration, respectively. Treatment with flumazenil (0.2 mg/kg, i.v.; 7 neurones), administered 20 min after midazolam, completely reversed the inhibition by midazolam of the BK-induced spinal lamina V neural responses and spontaneous neuronal activity. In contrast, a large dose of naloxone (1.0 mg/kg, i.v.; 6 neurones), administered 20 min after midazolam, failed to alter the midazolam-induced depressant effects on the nociceptive responses, at the spinal dorsal horn. Treatments with flumazenil (5 neurones) and naloxone (5 neurones) did not influence either the spontaneous or the BK-induced neuronal discharges, recorded in spinal lamina V cells. Midazolam depressed the nociceptive responses probably through its agonistic activity on the binding to the GABA-benzodiazepine-barbiturate system in the spinal dorsal horn.

The effects of composition of subarachnoid gas space and anesthetic gas mixture on cerebrospinal fluid pressure changes during cisternography for transsphenoidal craniectomy.

The effects of gas composition in the subarachnoid space (injection of air or N(2)O) and in an anesthetic gas mixture (inhalation with or without N(2)O) on cerebrospinal fluid pressure were studied in 22 patients with pneumocisternography for transsphenoidal craniectomy. N(2)O (66%) anesthesia for 10 min increased cerebrospinal fluid pressure by up to 150% in 7 patients who were intrathecally injected with air. Withdrawal of N(2)O from the anesthetic gas mixture for sixty minutes reduced cerebrospinal fluid pressure to the initial pressure. A second N(2)O administration to the anesthetic gas mixture did not elevate cerebrospinal fluid pressure by as much as the first N(2)O administration. In 7 patients receiving subarachnoid air injection, replacing 66% N(2)O with 66% nitrogen prevented the change in cerebrospinal fluid pressure throughout the operation. In 8 patients N(2)O anesthesia and N(2)O intrathecal injection failed to eliminate the rise in cerebrospinal fluid pressure in 8 patients. Withdrawal of N(2)O from the anesthetic gas mixture for 60 min is recommended to prevent an extreme increase in cerebrospinal fluid pressure during pneumocisternography.

[Effects of prostacyclin (PGI2) on the hypoxic pulmonary vasoconstriction in dogs].

Effects of exogenous PGI2 on the hypoxic pulmonary vasoconstriction (HPV) were investigated by measuring %QLLL and the ratio of the left lower lobe blood flow (QLLL) to the total pulmonary blood flow (QT), in separately ventilated canine in vivo model. With PGI2 infusion, %QLLL, that had decreased from 20.7 +/- 1.9% to 4.1 +/- 1.1% by the hypoxic gas ventilation, gradually increased to 16.4 +/- 3.2% at the maximum dose (1.0 micrograms kg-1. min-1). Simultaneously both pulmonary artery pressure and PaO2 decreased significantly. Systemic blood pressure dropped markedly but cardiac output remained at the initial level. These results suggest that exogenous PGI2 improves the pulmonary circulation by reducing pulmonary hypertension induced with HPV, while PGI2 induces hypoxia by inhibiting HPV response and systemic hypotension by dilating the peripheral resistance vessels. Therefore, we have to consider these two opposite effects of PGI2 on its clinical application.

Effect of preanesthetic famotidine on gastric volume and pH.

The effect of preanesthetic 20 mg of famotidine on gastric fluid volume and pH were studied in patients scheduled for elective surgery. One hundred and twenty-eight patients were divided into four groups-control, intravenous, intramuscular and oral with 32 patients in each group. Patients in placebo group received no famotidine and served as control. Patients in the intravenous and intramuscular groups were administered famotidine one hour before surgery. Patients in the oral group were administered famotidine the night before and on the morning of surgery. Gastric volume in the control group was 19.1 +/- 10.8 ml; in the intravenous group, 7.4 +/- 6.4 ml; in the intramuscular group, 7.3 +/- 6.9 ml; and in the oral group, 7.1 +/- 6.9 ml. Gastric pH was 3.4 +/- 2.3, 6.8 +/- 1.1, 6.9 +/- 1.6, and 6.7 +/- 1.2 in groups one through four, respectively. When compared to the control group, famotidine significantly decreased gastric volume and increased gastric pH. There were no statistical differences among the different modes of administration. No adverse effects were observed in this study. It is concluded that preanesthetic management of 20 mg of famotidine reduced the risk of acid aspiration pneumonitis.

Indirect and direct suppressive actions of morphine on dorsal horn neurons in rabbits.

The analgesic mechanism of morphine on the spinal nociceptive transmission was compared in rabbits with the intact and cold-blocked states of the spinal cord. The degree of the suppressive effect of morphine (2 mg/kg) on the bradykinin-induced activity was significantly greater in the intact than in the cold-blocked states. Morphine (4 mg/kg) suppressed the nociceptive responses to similar levels in both states. These results suggest that in a small dose, the indirect suppressive action is more important than the direct action. In a larger dose, the suppressive action is probably exerted primarily by the direct spinal action.