Milrinone, a phosphodiesterase III inhibitor, prevents reduction of jugular bulb saturation during rewarming from hypothermic cardiopulmonary bypass.

INTRODUCTION: Inadequate cerebral oxygen balance during cardiopulmonary bypass may cause neuropsychological dysfunction. Milrinone, a phosphodiesterase III inhibitor, augments cerebral blood flow by direct vasodilatation. We conducted a prospective, randomized study in patients undergoing cardiac surgery with cardiopulmonary bypass to clarify the clinical efficacy of milrinone in the imbalance of cerebral oxygen supply and demand during the rewarming period of cardiopulmonary bypass. METHODS: This is a prospective, randomized and placebo-controlled study. After anesthesia, a 5.5 F fiberoptic oximeter catheter was inserted into the right jugular bulb retrogradely for monitoring the jugular venous oxyhemoglobin saturation (SjO(2)). Patients were randomly assigned to two groups, one receiving a continuous infusion of milrinone, 0.5 µg/kg/min during hypothermic cardiopulmonary bypass, and the other receiving saline as control. RESULTS: Milrinone significantly prevented the reduction of the jugular venous oxyhemoglobin saturation at 10 minutes from the start of rewarming compared with the control group, but did not do so from 10 to 20 minutes after rewarming. CONCLUSION: Milrinone suppresses the reduction of SjO(2) and improves the balance of cerebral oxygen supply and demand during the early rewarming period of hypothermic cardiopulmonary bypass.

Small temperature variations alter edaravone-induced neuroprotection of cortical cultures exposed to prolonged hypoxic episodes.

BACKGROUND: Edaravone, a free radical scavenger, has been shown to be neuroprotective in vivo and in vitro. However, the impact of small temperature variations on its neuroprotective actions remains unknown. METHODS: We examined the degree of neuroprotection conferred by various concentrations of edaravone on cortical cultures exposed to prolonged hypoxia (24 h) under three conditions: mild hypothermia (32 degrees C), normothermia (37 degrees C), and mild hyperthermia (39 degrees C). The survival of cortical neurones from E16 Wistar rats (SR) was evaluated using photomicrographs taken before and after exposure to hypoxia. RESULTS: The mean survival of neurones exposed to hypoxia at normothermia was 14.7 (sem 1.8)%. The addition of 50 microM edaravone significantly improved the mean survival to 40.5 (4.7)%. This improvement was noted at higher doses of edaravone (5 microM < or =) but not at lower doses (< or =500 nM). With mild hypothermia and prolonged hypoxia without edaravone, neuroprotection was significantly improved with a mean survival of 63.0 (5.2)%. This neuroprotective effect was not enhanced with the addition of edaravone, even at the highest dose. Hypoxia-induced neurotoxicity was aggravated by mild hyperthermia as reflected by a mean survival of 9.1 (2.1)%. However, higher concentrations of edaravone inhibited the deleterious effect of mild hyperthermia, thereby demonstrating a significant neuroprotective effect. The survival of neurones subjected to both hyperthermia and edaravone was the same as that of neurones exposed to normothermia and edaravone. CONCLUSIONS: Temperature is a potential factor in determining whether edaravone confers a neuroprotective effect when applied during prolonged hypoxic insults.

The antiarrhythmic effect of centrally administered rilmenidine involves muscarinic receptors, protein kinase C and mitochondrial signalling pathways.

BACKGROUND AND PURPOSE: We have previously demonstrated that stimulation of imidazoline receptors in the CNS prevented halothane-adrenaline arrhythmias during halothane anaesthesia and that stimulation of the vagus nerve may be critical to this effect. However, details of the mechanism(s) involved are not yet available. The present study was designed to examine the role of muscarinic receptors, protein kinase C (PKC), ATP-sensitive potassium channels (K(ATP)) and the mitochondrial permeability transition pore (MPTP) in the antiarrhythmic effect of rilmenidine, an imidazoline receptor agonist. EXPERIMENTAL APPROACH: Rats were anaesthetized with halothane and monitored continuously for arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of adrenaline was defined as the lowest dose producing three or more premature ventricular contractions within a 15-s period. We confirmed that centrally administered rilmenidine prevented halothane-adrenaline arrhythmias and then examined the antiarrhythmic effect of rilmenidine in the presence of atropine methylnitrate, a muscarinic receptor antagonist, calphostin C, a PKC inhibitor, HMR-1098, a sarcolemmal K(ATP) inhibitor, 5-hydroxydecanoic acid, a mitochondrial K(ATP) inhibitor or atractyloside, an MPTP opener. KEY RESULTS: The antiarrhythmic effect of rilmenidine was significantly inhibited by atropine methylnitrate, calphostin C, 5-hydroxydecanoic acid and atractyloside, but the effects of HMR-1098 in our model were not clear. CONCLUSIONS AND IMPLICATIONS: The present results suggest that muscarinic receptors, PKC, mitochondrial K(ATP) channels and MPTP may be crucial components of the mechanism involved in the antiarrhythmic effect of rilmenidine given into the CNS.

The involvement of pertussis toxin-sensitive G proteins in the post receptor mechanism of central I1-imidazoline receptors.

1. To elucidate the possible involvement of pertussis toxin (PTX)-sensitive G proteins in the post receptor mechanism of alpha 2-adrenoceptors and imidazoline receptors, we examined the effect of pretreatment of the central nervous system with PTX on the antidysrhythmic effect of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, and rilmenidine, a selective I1-imidazoline receptor agonist on halothane-adrenaline dysrhythmias in rats. 2. Dexmedetomidine (0, 1.0, 2.0, 5.0 micrograms kg-1 min-1.i.v.) and rilmenidine (0, 1.0, 3.0, 10, 20 micrograms kg-1, i.v.) prevented the genesis of halothane-adrenaline dysrhythmias in a dose-dependent fashion. Both idazoxan (10, 20 micrograms kg-1, intracerebroventricularly (i.c.v.)), an alpha 2-adrenoceptor antagonist with high affinity for imidazoline receptors, and rauwolscine, (40 micrograms kg-1, i.c.v.), an alpha 2-adrenoceptor antagonist with low affinity for imidazoline receptors inhibited the action of dexmedetomidine (5.0 micrograms kg-1, min-1, i.v.), but the inhibitory potency of idazoxan was much greater than that of rauwolscine. While the pretreatment with PTX (0.1, 0.5, 1.0 micrograms kg-1, i.c.v.) did not change the dysrhythmogenecity of adrenaline, this treatment completely blocked the antidysrhythmic property of rilmenidine (20 micrograms kg-1, i.v.) as well as dexmedetomidine (5.0 micrograms kg-1 min-1, i.v.). 3. It is suggested that central I1-imidazoline receptors as well as alpha 2-adrenoceptors may be functionally coupled to PTX-sensitive G proteins.

Antiarrhythmic action of rilmenidine on adrenaline-induced arrhythmia via central imidazoline receptors in halothane-anaesthetized dogs.

1. To elucidate the role of central imidazoline receptors in the genesis of adrenaline-induced arrhythmias under halothane anaesthesia, we investigated the effects of rilmenidine, a selective agonist at imidazoline receptors, on this type of arrhythmia in dogs. Rilmenidine (1, 3, 10 micrograms kg-1, i.v.) did not affect basal haemodynamic parameters (heart rate and blood pressure), but dose-dependently inhibited adrenaline-induced arrhythmias under halothane anaesthesia. 2. Although, rilmenidine has a weak affinity for alpha(2)-adrenoceptors, pretreatment with idazoxan (10 micrograms kg-1, intracisternally i.c.), an imidazoline receptor antagonist which has also alpha(2)-adrenoceptor blocking potency, blocked the antiarrhythmic effect of rilmenidine (10 micrograms kg-1, i.v.). In contrast, pretreatment with rauwolscine (20 micrograms kg-1, i.c.), a classical alpha(2)-adrenoceptor antagonist with little affinity for imidazoline receptors, did not affect the effect of rilmenidine (10 micrograms kg-1, i.v.). Furthermore, bilateral vagotomy completely blocked the antiarrhythmic action of rilmenidine (10 micrograms kg-1, i.v.). 3. It is suggested that the antiarrhythmic action of rilmenidine is due to the activation of central imidazoline receptors and that vagal tone is critical for this action of rilmenidine.

Effect of local anaesthetics on the stimulus-secretion coupling in bovine adrenal chromaffin cells.

This study was carried out to determine the relative potencies of local anesthetics to inhibit the cholinergic synaptic transmission using cultured bovine adrenal chromaffin cells, and to clarify if the inhibitory action would correlate with biophysical and pharmacological properties. Local anaesthetics (bupivacaine, etidocaine, tetracaine, lignocaine and procaine; 0.02-2 mM) inhibited carbachol-induced catecholamine release from the cells in a concentration-dependent manner. This inhibition was completely reversible. IC50 (concentration of 50% inhibition) of each anaesthetic showed no correlation with the lipid solubility. The local anaesthetics showed greater inhibitory potency at a higher extracellular pH. The results suggest that clinically relevant concentrations of local anaesthetics inhibit the stimulus-secretion coupling in the chromaffin cells. The un-ionized based form plays a major role, and the inhibitory potency does not depend on the lipid solubility of the anaesthetics.

[A hypertensive crisis during surgery in a patient with neuroblastoma].

Neuroblastoma is the most common solid tumour in infancy and childhood. The tumour usually produces large amounts of catecholamines. Few patients with neuroblastoma, however, were reported to have become hypertensive because of catecholamine metabolism within the tumour itself. This is one of the most important differences compared with pheochromocytomas. We experienced a hypertensive crisis accompanied by tachycardia and an increase in the plasma catecholamine concentration during surgery in a patient with neuroblastoma. The plasma catecholamine level was comparable to that of pheochromocytoma. Phentolamine and propranolol were effective to control the hypertension and tachycardia.

[Electron microscopic study on the tissue reaction after root canal filling following artificial periapical lesions--about periapical lesions induced by carrageenin].

Although a number of reports on the formation of periapical lesions have been down, little study on the healing stage of this one is seen. Therefore, the aim of this study was to investigate the changes of the fine structure of the healing stage of the artificial periapical lesions after root canal filling and to make an experimental model for the further screening test of various kinds of medicaments and materials for root canal treatment and root canal filling. In this study, the first mandibular molars of male Wistar strain rats were used. Periapical lesions were induced by 0.5% carrageenin and after three weeks, the root canals of the first molars were filled with gutta-percha points and sealers. Then, the healing stage of the periapical lesion was observed light microscopically, electron-microscopically and enzyme (alkaline phosphatase, ALP, and acid phosphatase, ACP)-histochemically. The results were as follows after the root canal filling with carrageenins: 1. At 1 to 7 days, a great number of neutrophils and histiocytes were observed and expansion of periapical lesions caused by the irritation followed by root canal filling was observed. 2. At 2 to 3 weeks, a great number of leukocytes, histiocytes and fibroblasts were observed in the vicinity of the root apex. 3. At 4 to 5 weeks, a great number of histiocytes and mast cells were observed and granulated tissues of the periapical lesions had a tendency to become fibrosis and new calcified cement increased at the root apex. 4. At 7 to 10 weeks, the fibroblast granulation tissue around the periapical lesions synthesized active collagen fibers and the deposition of new alveolar bone was seen within the resorbed alveolar bone. 5. At 15 to 20 weeks, the periapical lesions could be thought to be healing histopathologically although some of inflammatory cells were seen 20 weeks after treatment. 6. At 10 weeks, strong positive responses of ALP were recognized. At 20 weeks, the general appearance of both the ALP and ACP staining showed almost the same response as that of normal periodontium. 7. As for the prognosis, "over filling" showed better healing than that of "under filling". 8. In the case which the root apex was fractured, inflammation lasted for a long period.

Evaluation of diagonal earlobe crease as a marker of coronary artery disease: the use of this sign in pre-operative assessment.

In this study, we examined the usefulness of the earlobe crease sign as a marker of coronary artery disease in the pre-operative assessment of patients. We were interested in evaluating this sign for use in emergency patients. We investigated 530 patients, aged > 40 years, undergoing elective surgery. If the electrocardiogram was abnormal or the patient reported symptoms suggesting coronary artery disease, further cardiac examinations were performed. Patients who demonstrated evidence of coronary artery disease in the additional investigations or had a clear history of coronary artery disease were classified as the abnormal coronary group. Other patients with no history and/or normal investigations were classified as the normal coronary group. The assessment of earlobe crease sign was performed prior to anaesthesia, and the sensitivity, specificity and positive predictive value of this sign were calculated. We found that the sensitivity and specificity was high regardless of age, except for specificity in patients > 70 years old. The data suggest that the earlobe crease sign may be a useful marker for the presence of coronary artery disease in patients undergoing emergency operations in which little or no history and investigations are available. However, more work is required to assess the use of this sign in other ethnic groups.

Preservation of collagen-induced whole blood platelet aggregation by tranexamic acid therapy in primary cardiac valve surgery.

Haemostatic disorder is one of the most common complications following cardiac surgery with cardiopulmonary bypass (CPB). Tranexamic acid reduces blood loss and allogeneic blood transfusion requirement in cardiac surgery. It had been thought that tranexamic acid inhibited fibrinolysis alone following CPB. In the present study, the haemostatic effects of tranexamic acid (20 mg/kg body weight bolus after induction of anaesthesia followed by continuous infusion at 2 mg/kg/h), including fibrinolysis and platelet function, were investigated in 22 patients (tranexamic acid group n = 12; control group n = 10) undergoing primary cardiac valve surgery. Fibrinolysis following CPB was reduced significantly in the tranexamic acid group. Following protamine administration, the reduction of collagen-induced whole blood platelet aggregation was mitigated significantly in the tranexamic acid group compared with the control group (36% reduction in the tranexamic acid group vs 58% in the control group; p = 0.011), although platelet counts did not differ between the two groups. In conclusion, tranexamic acid not only inhibits fibrinolysis directly, but also may preserve platelet function following CPB.

Adrenoceptor mechanism involved in thiopental-epinephrine-induced arrhythmias in dogs.

The authors investigated the role of alpha 1- and beta-adrenoceptors on induction of ventricular arrhythmias during thiopental anesthesia in dogs and compared with that during halothane anesthesia. Throughout this study, arrhythmogenic threshold of epinephrine during thiopental anesthesia was designed to be comparable with that during halothane anesthesia. Phenylephrine, an alpha 1-agonist, and isoproterenol, a beta-agonist, consistently failed to provoke arrhythmias during thiopental or halothane anesthesia. The interaction between phenylephrine and isoproterenol in inducing arrhythmias was synergistic and additive during halothane and thiopental anesthesia, respectively, indicating that adrenoceptor mechanism in thiopental-epinephrine arrhythmias is different from that in halothane-epinephrine arrhythmias. During thiopental anesthesia, incidence of arrhythmias with blood pressure elevation by epinephrine, phenylephrine, or angiotensin II was not different, and increasing heart rate by electrical pacing did not replace isoproterenol in the arrhythmogenic interaction between isoproterenol and phenylephrine. The results indicate that blood pressure elevation due to the combined inotropic action of alpha 1- and beta-adrenoceptor agonists is a critical factor in the genesis of thiopental-epinephrine arrhythmias.

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.

Laser Doppler skin blood flow and sympathetic nervous responses to surgical incision during halothane and isoflurane anesthesia.

The aim of the present study was to evaluate whether a sudden decrease in skin blood flow measured using a laser Doppler velocimeter reflects sympathetic nervous response to surgical skin incision during halothane (n = 17) and isoflurane (n = 16) anesthesia in 33 ASA physical status I or II patients scheduled for laparotomy. Plasma norepinephrine concentrations in the responding patients who showed a sudden decrease in the skin blood flow after surgical incision increased significantly and continued to increase 1-10 min after skin incision under halothane and isoflurane anesthesia. Although plasma norepinephrine concentrations in the nonresponders did not increase after surgical incision with halothane, the concentrations increased significantly at 1 min, but not at 3 and 10 min, after skin incision with isoflurane. The results indicate that the sudden decrease in laser Doppler flow reflects the sympathetic response to surgical incision. However, these also suggest that the factors that control the skin blood flow may not be simply sympathetic but may reflect other modulators as well. Plasma epinephrine concentration increased during skin incision, but the concentrations did not differ between the patients with and without a sudden decrease in skin blood flow. Increases in systolic blood pressure and rate-pressure product on skin incision were also significantly more in patients with skin blood flow response compared with those without the response. The magnitude of changes in plasma norepinephrine concentration and hemodynamic variables with skin incision was greater with isoflurane than with halothane at the same minimum alveolar anesthetic concentration level.

Myocardial epinephrine sensitization with subanesthetic concentrations of halothane in dogs.

The authors investigated myocardial epinephrine sensitization by subanesthetic concentrations of halothane. The dose-response relationship for the action of halothane was examined with etomidate plus varying subanesthetic concentrations of halothane in dogs. The arrhythmogenic threshold of epinephrine was decreased in a dose-dependent manner at end-tidal concentrations of halothane between 0.1 and 0.3%. At end-tidal halothane is greater than 0.3%, and no further reduction of arrhythmogenic threshold of epinephrine occurred. The plasma concentrations of epinephrine producing four or more premature ventricular contractions in 15 s were 201.3 +/- 34.3, 98.1 +/- 13.9, 60.3 +/- 8.63, 57.9 +/- 12.8, 54.5 +/- 8.61, and 53.9 +/- 4.86 ng/ml (mean +/- SEM), at 0, 0.1, 0.3, 0.5, 1.0, and 1.5% of halothane at end-tidal concentrations, respectively. The results suggest that in the presence of etomidate, halothane produces myocardial sensitization to epinephrine at subanesthetic concentrations as low as 0.1%. Increasing halothane to 0.3% produces a further reduction in the arrhythmogenic dose of epinephrine.

Selective beta 1 and beta 2 adrenoceptor blockade on epinephrine-induced arrhythmias in halothane anaesthetized dogs.

Beta 2 as well as beta 1 adrenoceptors have been recognized in the heart of vertebrates. They mediate a positive chronotropic action of catecholamines. We compared the effect of selective beta 1 and beta 2 adrenoceptor antagonists on the genesis of halothane-epinephrine arrhythmias in dogs. The arrhythmogenic dose (AD) of epinephrine was increased in the presence of l-metoprolol, a selective beta 1 antagonist (8.40 +/- 1.13 micrograms.kg-1 x min-1; mean +/- SEM), compared with control value (2.62 +/- 0.56) (P < 0.05). In contrast, ICI-118,551, a selective beta 2 antagonist, did not change the AD (2.36 +/- 0.43). Adding ICI-118,551 to l-metoprolol did not affect the AD of epinephrine in the presence of l-metoprolol alone (6.34 +/- 0.74 vs 8.40 +/- 1.13). These results suggest that selective beta 1 blockade is effective in preventing halothane-epinephrine arrhythmias, but selective beta 2 blockade is not.

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.

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.

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.