Biomedical subjects

I Yoshiya

Publications and source records attributed to I Yoshiya.

At least 91 records · Page 5Linked to original sources

PubMed1995

Analgesic and hypnotic effects of subanaesthetic concentrations of xenon in human volunteers: comparison with nitrous oxide.

The purpose of this study was to examine the effects of xenon and nitrous oxide in equipotent doses of 0.3 MAC on pain threshold and auditory response time in six healthy male volunteers. Compared with 100% oxygen inhalation, xenon and nitrous oxide significantly increased the pain threshold as measured by a radiant heat algometer. There was no significant difference in analgesic effects between xenon and nitrous oxide. Xenon significantly prolonged the response time to auditory stimuli compared with 100% oxygen, but nitrous oxide did not. The inhibitory effect of xenon on the auditory response time was significantly greater than that of nitrous oxide. The same six volunteers were studied to test if naloxone antagonized analgesia induced by xenon or nitrous oxide. The analgesic effects of xenon and nitrous oxide did not differ with or without naloxone.

Adult↗

PubMed1995

Thoracic epidural anesthesia attenuates halothane-induced myocardial sensitization to dysrhythmogenic effect of epinephrine in dogs.

BACKGROUND: The autonomic nervous system plays a critical role in the central modulation of cardiac dysrhythmias. Because sympathetic blockade by thoracic epidural anesthesia has been documented to protect patients from various stress responses, the authors speculate that epidural anesthesia can attenuate the dysrhythmogenic interaction between halothane and epinephrine. METHODS: In adult mongrel dogs anesthetized with halothane, the dysrhythmogenic dose (DD) of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, was determined in the presence of thoracic epidural mepivacaine or saline. To address the effect of circulating mepivacaine after epidural administration, the authors examined the DD of epinephrine in the presence of intravenous mepivacaine. They also investigated the effect of thoracic epidural anesthesia in bilaterally vagotomized dogs. RESULTS: Epidural mepivacaine significantly increased the DD of epinephrine compared with epidural saline. However, intravenous mepivacaine did not affect the DD of epinephrine, even when the plasma concentration of mepivacaine during the dysrhythmias was twice that in the epidural mepivacaine group. The beneficial effect of epidural mepivacaine was not seen in bilaterally vagotomized dogs. CONCLUSIONS: Thoracic epidural anesthesia attenuated the myocardial sensitization by halothane, and vagal activity had an essential role in this action.

Anesthesia, Epidural↗

PubMed1995

Role of the vagus nerve in the antidysrhythmic effect of dexmedetomidine on halothane/epinephrine dysrhythmias in dogs.

BACKGROUND: Dexmedetomidine, an alpha 2-adrenergic agonist, can prevent the genesis of halothane/epinephrine dysrhythmias through the central nervous system. Because stimulation of alpha 2 adrenoceptors in the central nervous system enhances vagal neural activity and vagal stimulation is known to inhibit digitalis-induced dysrhythmias, dexmedetomidine may exert the antidysrhythmic property through vagal stimulation. To address this hypothesis, the effect of dexmedetomidine in vagotomized dogs was examined and compared with that in intact dogs. In addition, the effect of vagotomy on the antidysrhythmic action of doxazosin, an alpha 1 antagonist, was studied. METHODS: Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and premature ventricular contractions. Animals were divided into two groups receiving bilateral vagotomy or sham operation. The dysrhythmia threshold was expressed by the dysrhythmogenic dose of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, and plasma concentration of epinephrine at the time when the dysrhythmogenic dose was reached. The threshold was determined in the presence of dexmedetomidine (a selective alpha 2 agonist that crosses the blood-brain barrier) and doxazosin (a selective alpha 1 antagonist that does not penetrate the blood-brain barrier) in the two groups. In addition, the effect of dexmedetomidine in the presence of atropine methylnitrate instead of vagotomy was examined. RESULTS: Vagotomy did not affect the basal vulnerability to halothane/epinephrine dysrhythmias significantly. Although dexmedetomidine dose-dependently prevented the genesis of the dysrhythmias in intact dogs, the beneficial effect of dexmedetomidine was abolished in both the vagotomized and the atropine-treated dogs. On the other hand, vagotomy did not change the antidysrhythmic property of doxazosin. CONCLUSIONS: The vagus nerve plays an important role in the prevention of halothane/epinephrine dysrhythmias by dexmedetomidine in dogs. However, resting vagal tone neither modulates the onset of halothane/epinephrine dysrhythmias nor affects the antidysrhythmic action of doxazosin.

Adrenergic alpha-Agonists↗

PubMed1995

Further characterization of the receptor mechanism involved in the antidysrhythmic effect of dexmedetomidine on halothane/epinephrine dysrhythmias in dogs.

BACKGROUND: alpha 2 Adrenoceptors in the central nervous system mediate various physiologic processes, including cardiovascular control. Recently, some of these actions have been reported to be mediated by a nonadrenergic receptor, namely an imidazoline receptor. The authors previously reported that dexmedetomidine, a selective alpha 2 agonist, prevents the genesis of halothane-epinephrine dysrhythmias through a central mechanism. Because dexmedetomidine also binds to imidazoline receptors, we performed the current study to examine the precise receptor mechanism involved in the antidysrhythmic property of dexmedetomidine. METHODS: Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and premature ventricular contractions. The dysrhythmogenic dose of epinephrine was defined as the smallest dose producing four or more premature ventricular contractions within 15-s period. We examined the antidysrhythmic action of dexmedetomidine in the presence of two kinds of alpha 2 antagonists, that is, agents that label imidazoline receptors and exert a pharmacologic action through imidazoline receptors (idazoxan and atipamezole) and agents that are nonimidazoline compounds and are lacking in pharmacologic action through imidazoline receptors (rauwolscine and L-659,066). They were given cerebroventricularly. RESULTS: Idazoxan and atipamezole significantly inhibited the antidysrhythmic action of dexmedetomidine, whereas rauwolscine and L-659,066 did not. CONCLUSIONS: Because alpha 2 antagonists having imidazoline or imidazole structures inhibited the antidysrhythmic action of dexmedetomidine, and the inhibition produced by the non-imidazoline alpha 2 antagonists was not significant, imidazoline receptors in the central nervous system are more responsible for the antidysrhythmic action of dexmedetomidine than are alpha 2 adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1995

A comparative evaluation of pressure-triggering and flow-triggering in pressure support ventilation (PSV) for neonates using an animal model.

The triggering system in pressure support ventilation needs to respond rapidly, especially in neonates. The aim of this study was to compare the effects of flow-triggered and pressure-triggered pressure support ventilation on neonatal mechanical ventilation using an animal model. Respiratory flow, airway pressure, oesophageal pressure, and diaphragmatic electromyogram were measured during pressure support ventilation in five anaesthetized rabbits. The animals were connected to a VIPBIRD (Bird, U.S.A.) (CPAP mode, pressure support ventilation, 5 cm H2O and PEEP 0 cm H2O). Flow-triggering sensitivity was set at 0.2l/min, 0.5l/min, 1.01l/min, or 1.5l/min. Pressure-triggering sensitivity was set at -1.0 cm H2O. Shorter trigger delay and longer pressure support time were observed in flow-triggering. There was also less diaphragmatic activity in flow-triggering as evidenced by the amplitude of integrated diaphragmatic electromyogram and negative deflection of oesophageal pressure. The findings suggest that flow-triggering will prove superior to pressure-triggering in pressure support ventilation for neonates.

Animals↗

PubMed1995

Rilmenidine prevents epinephrine-induced arrhythmias in halothane-anesthetized dogs.

Stimulation of central alpha 2-adrenoceptors has been known to prevent epinephrine-induced arrhythmias in halothane-anesthetized dogs. Because recent studies suggested that several physiological processes that were traditionally attributed to activation of alpha 2-adrenoceptors, such as hypotensive action, are mediated through imidazoline receptors (IRs), it may be likely that IRs are involved in the antiarrhythmic action. We investigated the hypotensive effect of rilmenidine, a selective IR agonist (1, 3, and 10 micrograms/kg i.v.), and the antiarrhythmic effects of the drug on epinephrine-induced arrhythmias during halothane anesthesia in dogs. Although the hypotensive effect of rilmenidine was not remarkable in the dose range we tested, rilmenidine increased the arrhythmogenic threshold for epinephrine in a dose-dependent manner during halothane anesthesia, achieving statistical significance at 10 micrograms/kg, the highest dose we examined. These results suggest that rilmenidine prevents epinephrine-induced arrhythmias during halothane anesthesia and that this effect is more potent than its hypotensive action.

Adrenergic alpha-Agonists↗

PubMed1994

Effects of sympathectomy on the cutaneous temperature abnormalities in rats with chronic constriction injury of the sciatic nerve.

Effects of surgical sympathectomy on the cutaneous temperature abnormalities of plantar surface evoked by the chronic constriction injury (CCI) of the sciatic nerve were investigated in the rat. In normal animals, there were very small temperature differences between both plantar surfaces. There were also very small temperature differences in plantar surfaces following the sympathectomy prior to CCI. In rats with CCI, the cutaneous temperature of the nerve-injured plantar surface was significantly higher (warmer) than that of the contralateral plantar surface during the first week following CCI, and then became lower (cooler). Surgical sympathectomy prior to and just after CCI significant suppressed the temperature abnormalities during the first week, but no effect was observed after 2 weeks following CCI. These observations indicate that sympathetic vasoconstriction may contribute to the cutaneous temperature abnormalities evoked by CCI during the early stage, but does not affect the abnormalities at later stages.

Animals↗

PubMed1994

Comparison of inspiratory work of breathing between flow-triggered and pressure-triggered demand flow systems in rabbits.

OBJECTIVES: Flow-triggered continuous positive airway pressure decreases the inspiratory work of breathing in adults when compared with pressure-triggered continuous positive airway pressure. However, the effect of flow-triggered continuous positive airway pressure on work of breathing in neonates is not known. Our objective was to determine if flow-triggering was superior to pressure triggering in the presence of narrow endotracheal tubes, such as those tubes used in neonates. DESIGN: Prospective evaluation using within-animal comparison of flow-triggering and pressure-triggering demand flow systems. SETTING: The animal laboratory in a university hospital. SUBJECTS: Six spontaneously breathing white rabbits, tracheostomized and intubated with 3- and 4-mm inner diameter endotracheal tubes. INTERVENTIONS: The animals were connected to a ventilator through a standard respiratory circuit. The ventilator was randomly operated in the following modes: flow-triggered continuous positive airway pressure, pressure-triggered continuous positive airway pressure, flow-triggered with 5 cm H2O pressure support ventilation, and pressure-triggered with 5 cm H2O pressure support ventilation. MEASUREMENTS AND MAIN RESULTS: Esophageal pressure, airway pressure, and flow signals were monitored. Control data were obtained while the rabbits were breathing room air through the endotracheal tube. With 3-mm inner diameter endotracheal tubes, the negative deflection of esophageal pressure during flow-triggered continuous positive airway pressure was significantly less than control; however, negative deflection of esophageal pressure during pressure-triggered continuous positive airway pressure did not significantly differ from control. The application of 5 cm H2O pressure support ventilation with flow-triggering decreased negative deflection of esophageal pressure significantly compared with flow-triggered continuous positive airway pressure, pressure-triggered continuous positive airway pressure, and control. With endotracheal tube inner diameter of 4 mm, flow-triggered continuous positive airway pressure and pressure-triggered continuous positive airway pressure did not show any differences compared to control. Negative deflection of esophageal pressure differed under all conditions except control when results with the 3-mm inner diameter endotracheal tube were compared with the 4-mm inner diameter endotracheal tube. CONCLUSIONS: Flow-triggering is superior to pressure-triggering in the presence of a 3-mm inner diameter endotracheal tube. This difference was not clear with a 4-mm inner diameter endotracheal tube. The size of the endotracheal tube may be the most important variable in evaluating the approach used to ventilate small neonates.

Air Pressure↗

PubMed1994

Comparative evaluation of diaphragmatic activity during pressure support ventilation and intermittent mandatory ventilation in animal model.

The aim of the present study is a comparative evaluation of the effects of pressure support ventilation (PSV) and intermittent mandatory ventilation (IMV) on diaphragmatic activity in rabbit model of neonate. The animals were divided into a PSV group and an IMV group. In the IMV group, spontaneous breathing and four kinds of IMV rate (5, 10, 15, and 20/min) were applied (Ventilator: Bear BP200, peak inspiratory pressure [PIP]: 12 cm H2O, inspiratory time: 0.6 s). In the PSV group, spontaneous breathing and four levels of PSV (3, 6, 9, and 12 cm H2O) were applied (Ventilator: VIP Bird, flow triggering). Airway pressure (Paw), flow (V), esophageal pressure (Pes), integrated diaphragmatic electromyogram (Edi), and arterial gas data were measured. Amplitudes of Pes and Edi were expressed as percentages (% Edi and % Pes) of the control value during spontaneous breathing to evaluate diaphragmatic activity. Lower IMV rates did not reduce diaphragmatic activity. Approximately half of diaphragmatic activity of control remained even at IMV 15/min. Diaphragmatic activity disappeared at IMV20/min. In contrast, PSV reduced Edi and Pes linearly according to support level. In conclusion, diaphragmatic activity could be reduced more gradually with PSV than IMV by altering ventilatory support level.

Animals↗

PubMed1994

Low plasma lidocaine concentration does not affect oxygen uptake at awakening from isoflurane anesthesia.

To clarify the effects of lidocaine in plasma after epidural administration on oxygen uptake (VO2) at awakening from isoflurane anesthesia, we measured VO2 in 45 patients undergoing abdominal hysterectomy under four conditions: control group, intravenous normal saline; epidural group, 3 mg/kg of 1.5% lidocaine epidurally as a bolus; and groups CIV-A and CIV-B, continuous intravenous infusion of 2% lidocaine, 0.5 and 1 mg/kg, respectively, for 5 min followed by 30 micrograms.kg-1 x min-1. VO2 at both periods of steady state during anesthesia before lidocaine administration and awakening from anesthesia were measured using a mass spectrometer system during spontaneous breathing. At awakening, VO2 in the control, CIV-A, and CIV-B groups increased significantly (P < 0.02) from 142 to 262-328 mL.min-1 x m-2 which as more (P < 0.01) than that in the epidural group which increased from 166 to 159 mL.min-1 x m-2. These results indicate that epidural lidocaine prevents the increase in VO2 associated with arousal from isoflurane anesthesia. This effect is not due to the absorbed plasma lidocaine but due to the epidural neural block.

Adult↗

PubMed1994

Epidural lidocaine delays arousal from isoflurane anesthesia.

To clarify the effect of epidural lidocaine on arousal from inhaled anesthesia, we investigated the minimum alveolar anesthetic concentration at awakening (MAC-Awake) of isoflurane and the duration between discontinuance of isoflurane inhalation and arousal from anesthesia in 60 female abdominal hysterectomy patients. All patients received epidural catheterization and were randomly assigned to one of five groups. The control group, A, was given normal saline intravenously (IV) and epidurally. Group B was given 1 mg/kg of 2% lidocaine IV as a bolus. Groups C and D were given 0.5 and 1 mg/kg, respectively, of 2% lidocaine IV for 5 min, followed by 30 micrograms.kg-1.min-1. Group E was given 3 mg/kg of 1.5% lidocaine epidurally as a bolus. These doses of lidocaine or control saline were administered 15 min before the end of the surgical procedure. MAC-Awake values in Groups A, B, C, D, and E were 0.30% +/- 0.05%, 0.28% +/- 0.04%, 0.29% +/- 0.04%, 0.31% +/- 0.04%, and 0.18% +/- 0.05% (mean +/- SD), respectively. MAC-Awake in Group E was lower than in the other groups (P < 0.001). The duration until arousal in Group E (21.0 +/- 2.0 min) was longer than in Groups A, B, C, and D (12.6 +/- 1.8 min, 12 +/- 2.3 min, 13.3 +/- 2.5 min, and 14.3 +/- 2.7 min, respectively) (P < 0.001). Plasma lidocaine levels in Groups B, C, D, and E were 0.95 +/- 0.17 microgram/mL, 1.07 +/- 0.16 microgram/mL, 2.09 +/- 0.31 micrograms/mL, and 1.02 +/- 0.16 micrograms/mL, respectively. We conclude that analgesia produced by epidural lidocaine delays arousal from isoflurane anesthesia. Furthermore, lidocaine plasma levels are shown to be too low to cause any sedative effect, thus suggesting that postoperative pain may cause significantly faster arousal from anesthesia.

Adult↗

PubMed1994

Decrease in vecuronium infusion dose requirements by nicardipine in humans.

This study was designed to analyze quantitatively the interaction of nicardipine with vecuronium using a constant infusion technique. Forty-seven patients undergoing elective otolaryngeal surgery were anesthetized with isoflurane (1% end-tidal) and nitrous oxide (67%). Patients were randomly assigned to receive one of four doses of nicardipine (0, 1, 2, and 3 micrograms.kg-1.min-1). Vecuronium infusion dose requirement was determined as a constant infusion rate which maintained 90% depression of control twitch tension. Nicardipine significantly decreased the vecuronium requirement in a dose-dependent manner, i.e., the vecuronium doses were 0.70 +/- 0.03, 0.55 +/- 0.04, 0.42 +/- 0.04, and 0.37 +/- 0.05 micrograms.kg-1.min-1 at nicardipine doses of 0, 1, 2, and 3 micrograms.kg-1.min-1, respectively. Nicardipine also reduced both the plasma concentration of vecuronium to maintain the 90% depression and the total plasma clearance of vecuronium. The reversal of the vecuronium effect with neostigmine was not influenced by nicardipine. The results indicate that the vecuronium infusion dose requirements are reduced as much as 53% by a clinical dose of nicardipine.

Adult↗

PubMed1993

Persistent degenerative state of non-pyramidal neurons in the CA1 region of the gerbil hippocampus following transient forebrain ischemia.

Morphological changes in the neurons of the gerbil hippocampus following 5 min of forebrain ischemia were examined using light and electron microscopy. Although non-pyramidal neurons in the CA1 region of the hippocampus survived through the full length of the observation period, up to six weeks after ischemia, they consistently demonstrated degenerative changes distinct from those of the well-known "delayed neuronal death" of CA1 pyramidal cells. When examined with the light microscope, CA1 non-pyramidal neurons were found to be shrunken and their nuclei and cytoplasm were hyperchromatic between seven days and six weeks after ischemia. When examined with the electron microscope, postischemic non-pyramidal neurons were found to have markedly electron-dense profiles; their cytoplasm contained numerous free ribosomes and heterogeneous smaller granular substances, the latter also filling the nuclei. However, there was no loss of ribosomes from the rough endoplasmic reticulum, and mitochondrial cristae were preserved, suggesting that these neurons were viable. CA1 non-pyramidal neurons were studied immunohistochemically using three types of monoclonal antibodies, one each against parvalbumin, a nonphosphorylated epitope on the 168,000 mol. wt and 200,000 mol. wt subunits of neurofilament proteins, and microtubule-associated protein 2. CA1 non-pyramidal neurons lost immunoreactivity to these neuron-specific substances six weeks after ischemia, suggesting that these degenerating cells lacked certain types of normal neuronal activity. We conclude that non-pyramidal neurons in the hippocampal CA1 region survive transient ischemia but undergo degenerative changes following complete loss of CA1 pyramidal cells. These changes may be due to depletion of presumptive target-derived trophic factors within the non-pyramidal neurons.

Animals↗

PubMed1993

The effect of prostaglandin E1 on renal function after cardiac surgery involving cardiopulmonary bypass.

This study was performed to evaluate the effect of prostaglandin E1 (PGE1) on renal function after cardiac surgery in patients undergoing cardiopulmonary bypass (CPB). Haemodynamic and renal functional response to low dose PGE1 (0.02 microgram kg-1 min-1) (group A) or saline (group B) infusion via peripheral vein during CPB was evaluated in 20 patients who underwent cardiac surgery. The perfusion pressure was maintained at about 60 mmHg during CPB in both groups. Urine beta 2-microglobulin (UBMG) (P < 0.01), and urine N-acetyl-beta-D-glucosaminidase (NAG) (P < 0.05) demonstrated significantly high values after CPB in both groups compared with the presurgical value. Free water clearance (CH2O) decreased significantly at the first postoperative day compared with the pre-surgical value in both groups (P < 0.01). Statistical analysis of NAG, UBMG and CH2O demonstrated significant differences between both groups, in CH2O values at the third (P < 0.05) and fifth days (P < 0.05) after surgery, in NAG values at the fifty (P < 0.01) and seventh days (P < 0.01), and in UBMG values at the first (P < 0.05) and third (P < 0.05) postoperative day, respectively. Cardiac output (co) did not change in either group throughout this study. Pulmonary capillary wedge pressure (PCWP) in group A decreased significantly at 30 and 60 min after CPB, but in group B did not change throughout the study. Cardiac index (CI) decreased significantly at 60 min after CPB in group A (P < 0.05) and at 30 min in group B (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Alterations in pain threshold and psychomotor response associated with subanaesthetic concentrations of inhalation anaesthetics in humans.

We studied the effects of six inhalation anaesthetics at subanaesthetic concentrations of 0.2 MAC on pain threshold and psychomotor function in six healthy volunteers. When compared with 100% oxygen inhalation, nitrous oxide and methyoxyflurane significantly increased pain threshold as measured by a radiant heat algometer, and prolonged the response time to auditory stimuli. In contrast, halothane, enflurane, isoflurane and sevoflurane produced prolongation of the response time to auditory stimuli but did not influence pain perception. The pain threshold with nitrous oxide remained significantly increased 30 min after its discontinuation, while the response time returned to the preinhalation value. We conclude that nitrous oxide and methoxyflurane possess both analgesic and hypnotic actions but halothane, enflurane, isoflurane and sevoflurane do not have an analgesic action at subanaesthetic concentrations, and the analgesic action of nitrous oxide persists after its elimination.

Adult↗

PubMed1993

Role of imidazoline-preferring receptors in the genesis of epinephrine-induced arrhythmias in halothane-anesthetized dogs.

BACKGROUND: Drugs with a central alpha 2-adrenergic action can increase the threshold for halothane-epinephrine-induced arrhythmias. Recently, imidazoline-preferring receptors were shown to play a significant role in the hypotensive effect of alpha 2-adrenergic agonists containing an imidazole ring in their structure. To address the question of whether the antiarrhythmic property of the alpha 2-adrenergic agonists was caused by activation of alpha 2-adrenoceptors or imidazoline-preferring receptors in the central nervous system, the effect of an imidazoline (atipamezole) and a nonimidazoline (L-659,066 and yohimbine) alpha 2-adrenergic antagonist were examined as etiologic factors in the genesis of halothane-epinephrine-induced arrhythmias in dogs. METHODS: Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and for premature ventricular contractions. The arrhythmogenic dose (AD) of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, was determined in the presence of atipamezole (an imidazoline compound that acrosses the blood-brain barrier), L-659,066 (a nonimidazoline compound that does not penetrate the blood-brain barrier), and yohimbine (a nonimidazoline compound that passes the blood-brain barrier). These drugs were administered either intravenously or into the cisterna magna to assess the site of action for changes in responsiveness. RESULTS: Intravenous atipamezole decreased the AD of epinephrine in the dose-dependent fashion. However, neither L-659,066 nor yohimbine, administered peripherally, decreased the AD of epinephrine. Central administration of atipamezole also decreased the AD of epinephrine, while L-659,066, even if administered centrally, did not affect the AD of epinephrine in the presence of halothane. CONCLUSIONS: Because the imidazoline ring-containing alpha 2-adrenergic antagonist (atipamezole) potentiated the halothane-epinephrine-induced arrhythmias and the nonimidazole alpha 2-adrenergic antagonist (L-659,066 and yohimbine) did not, it is possible that the imidazoline-preferring, rather than the alpha 2-adrenergic, receptor is responsible for the antiarrhythmic property of alpha 2-adrenergic agonists.

Adrenergic alpha-Antagonists↗

PubMed1993

Comparative efficacy of antiarrhythmic agents in preventing halothane-epinephrine arrhythmias in rats.

BACKGROUND: Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na(+)-, K(+)- and Ca(2+)-channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats. METHODS: Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia in 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents. RESULTS: In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11.1 +/- 0.6, and 39.0 +/- 3.9 micrograms/kg, respectively, and the corresponding plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na(+)- and K(+)-channel blocker), E-4031 (K(+)-channel blocker), or amiodarone(K(+)-channel blocker with Na(+)-, Ca(2+)-, and beta-blocking activity) increased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 micrograms/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias induced by epinephrine, 16 micrograms/kg intravenously (P < 0.01). CONCLUSIONS: It was concluded that agents with K(+)-channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats.

Amiodarone↗

PubMed1993

Effects of prostaglandin E1 or trimethaphan on local cerebral blood flow and carbon dioxide reactivity during cerebral aneurysm surgery.

Effects of prostaglandin E1 (PGE1) or trimethaphan (TMP) on local cerebral blood flow (LCBF) and carbon dioxide (CO2) reactivity were studied in 26 patient undergoing cerebral aneurysm surgery for subarachnoid hemorrhage (SAH) under isoflurane anesthesia. Measurement of LCBF was made using a thermal gradient blood-flow meter. Hypotension was induced with a continuous i.v. infusion of PGE1 or TMP. The dose of PGE1 or TMP was adjusted to maintain the MAP at about 70 mm Hg, and CO2 reactivity was studied during and after PGE1 or TMP administration. PaCO2 was changed by the controlled hyperventilation. CO2 reactivity was evaluated by the following formula: % delta LCBF/delta PaCO2% mm Hg. Hypotensive drugs were discontinued at the completion of aneurysm clipping. Mean arterial pressure (MAP) decreased immediately after the start of either PGE1 or TMP. Heart rate (HR) did not change significantly in either group. LCBF decrease at 30 min after start of TMP administration (p < 0.05 compared with preinfusion value), whereas LCBF was unchanged during PGE1 administration. Neither PGE1 nor TMP affected CO2 reactivity during cerebral aneurysm surgery, whereas CO2 reactivity showed a close correlation with presurgical neurological status: before, rs = -0.523, p < 0.01; during, rs = -0.794, p < 0.01; after, rs = -0.643, p < 0.01. Comparison of the outcomes after aneurysm surgery demonstrated no significant difference between groups; however, there was a close correlation between presurgical neurological status and outcome in both groups (rs = 0.829, p < 0.01). These results suggest that PGE1 is preferable to TMP in inducing hypotension for cerebral aneurysm surgery because this drug maintains both LCBF and CO2 reactivity.

Adult↗