Colonic α2-adrenoceptor-mediated responses in the pony

The motor responses of the caecum and colon to stimulation of alpha 2-adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induced inhibition was preceded by a short period of increased smooth muscle basal tone as indicated by strain-gauge force transducer measurements. This pattern of activity was neither reversed nor prevented by the administration of tolazoline (10 micrograms/kg/min) intra-arterially. In contrast, inhibition of the colonic phasic and tonic motor activity by alpha 2-adrenoceptor stimulation was reversed competitively by tolazoline. The intra-arterial infusion of prostaglandin F2 alpha (10 micrograms/kg/min) induced prolonged and sustained spiking activity that might be related to signs of mild colic. Detomidine, and to a lesser extent xylazine, relaxed the whole of the large intestine and this was accompanied by alleviation of the signs of visceral pain.     

Involvement of α-adrenoreceptors in the regulation of omasal cyclic myoelectrical activity in sheep

In five conscious adult ewes at rest, chronically implanted with electrodes in the musculature of the omasal wall, intravenous (i.v.) infusion for 30 min of alpha 1- or alpha 2-adrenergic receptor blockers, prazosin (20 micrograms/kg/min) and yohimbine (30 micrograms/kg/min), respectively, had no significant effects on omasal myoelectrical activity. The i.v. administration for 15 min of alpha 1- or alpha 2-agonists phenylephrine (4 micrograms/kg/min) or naphazoline (2.5 micrograms/kg/min), respectively, increased the frequency and the amplitude of groups of myoelectrical discharges of omasum, as well as the duration of its activity. Pretreatment of animals with prazosin blocked the responses to phenylephrine. Yohimbine prevented the effects of naphazoline dose-dependently. It is suggested that both alpha 1- and alpha 2-adrenoreceptors are involved in regulation of the sheep's omasal notility. This regulation did not seem to be a simple consequence of the changes in the reticular motility.     

Central and peripheral β-adrenergic influences on reticulo-rumen and upper-gut myoelectrical activity in sheep

The effects of intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of beta-adrenoceptor agonists were evaluated on the reticulo-rumen and upper-gut myoelectrical activity in six ewes chronically fitted with intraparietal electrodes and a cannula in a lateral ventricle of the brain. Intravenous infusion of the beta 1 agonist dobutamine (30 micrograms/kg/min for 15 min) reduced the frequency of reticulo-ruminal and abomasal contractions and stimulated duodeno-jejunal motility, inducing a Phase III on the jejunum. These effects were reproduced by i.c.v. dobutamine at a dose of 10 micrograms/kg. Intravenous infusion of the beta 2 agonist ritodrine (15 micrograms/kg/min for 15 min) selectively inhibited antral and duodenal motility. Ritodrine i.c.v. (15 micrograms/kg) did not affect forestomach or gastrointestinal motility. The mixed beta 1, beta 2 agonist isoprenaline infused i.v. (0.6 micrograms/kg/min for 15 min) reproduced the effects of i.v. dobutamine, except at the antro-duodenal level which was strongly inhibited. The effects of i.v. dobutamine were antagonized by i.v. or i.c.v. acebutolol, a specific beta 1 antagonist. The effects of i.v. ritodrine were blocked by i.v. but not i.c.v. administration of propranolol, a mixed beta 1, beta 2 antagonist. These data indicate that the stimulation of central beta 1 adrenoceptors inhibits forestomach and antral motility and stimulates duodeno-jejunal motility. Stimulation of peripheral beta 2 adrenoceptors selectively inhibits duodeno-jejunal motility.     

Ibuprofen prevents Pasteurella hemolytica endotoxin-induced changes in plasma prostanoids and serotonin, and fever in sheep

Intravenous infusion of Pasteurella hemolytica endotoxin caused marked increases in the plasma levels of thromboxane B2 (TxB2), prostaglandins (PG) and serotonin in sheep. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin before endotoxin infusion averaged 283 +/- 53 (standard error of mean), 281 +/- 14 and 199 +/- 27 pg/ml and 57 +/- 3 ng/ml, respectively. At 50 min during endotoxin infusion, these values were increased to their maximum of 376, 339, 325 and 202% of control, respectively. Body temperature increased from the control value of 39.5 +/- 0.1 degrees C to a maximum of 41.5 +/- 0.1 degrees C at 200-300 min of infusion. In the second part of this study, we have examined the effects of ibuprofen on endotoxin-induced increases in plasma PG, TxB2, and serotonin levels and body temperature. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and temperature prior to ibuprofen and endotoxin infusion averaged 238 +/- 35, 335 +/- 44 and 248 +/- 28 pg/ml, 65 +/- 3 ng/ml and 40.1 +/- 0.2 degrees C, respectively. A loading dose (15 mg/kg) of ibuprofen was followed by infusion of endotoxin (12 micrograms/kg) and ibuprofen (43.3 mg/kg) over 500 min. Plasma levels of 6-keto-PGF1 alpha and serotonin increased only to 131 and 149% of control at 50 min of infusion, and levels of PGF2 alpha and TxB2 decreased to 50 and 80% of control at 100 and 150 min of infusion, respectively. Temperature remained unchanged. Ibuprofen effectively suppressed endotoxin-induced increases in the plasma levels of TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin and body temperature. It was concluded from the present study that nonsteroidal anti-inflammatory drugs as an adjunct to antibiotic therapy might have a rational basis in treatment of endotoxin toxicity.     

Probenecid infusion in mares: effect on para-aminohippuric acid clearance

Para-aminohippuric acid (PAHA, 0.1 mg/min/kg of body weight) was infused IV into 2 mares, followed by concurrent IV infusion of PAHA and probenecid (0.075, 0.15, 0.25, or 0.35 mg of probenecid/min/kg). Probenecid infusion reduced the clearance of PAHA at serum probenecid concentrations greater than 55 micrograms/ml. At 12-hour intervals, probenecid (in 5 repeated doses - 50, 75, 100, or 200 mg/kg) was administered by gavage to 2 mares. Mean serum probenecid concentration was greater than 55 micrograms/ml for all dosages. At dosages less than 200 mg/kg, accumulation of probenecid in the serum was minimal from the 1st to the 5th dose. At a dosage of 200 mg/kg, probenecid accumulated in the serum from the 1st to the 5th dose. Intragastric administration of 5 doses of probenecid (75 mg/kg) at 12-hour intervals to 6 mares reduced the clearance of PAHA by 50%. Bioavailability of probenecid was 117 and 102% for 2 mares after a single intragastric dose, compared with a single IV dose.     

Central and peripheral serotonergic control of forestomach motility in sheep

Participation of tryptaminergic receptors in the control of forestomach motility was investigated in conscious sheep using strain-gauges and chronically implanted electrodes. Two hours after feeding the sheep, serotonin (5-HT) was infused into the jugular vein (i.v.), or the carotid artery (i.c.), or into the lateral cerebral ventricles (i.c.v.), over a 10-min period. An i.v. dose of 16 micrograms/kg/min abolished the cyclic propagated contractions throughout the forestomach, increased ruminoreticular tone, and induced simultaneous contractions of all the parts of the rumen. A dose of 1.6 micrograms/kg/min i.c. or i.v. 5-HT inhibited phasic contractions. The effects of 5-HT were blocked completely by i.c.v. administration of methysergide (20 micrograms/kg) and imipramine (200 micrograms/kg), and blocked partially by naloxone (25 micrograms/kg), but unaffected by atropine (50 micrograms/kg). The inhibitory effects of i.v. 5-HT were antagonized by methysergide (200 micrograms/kg, i.v.) but unaffected by imipramine (2 mg/kg, i.v.) and atropine (250 micrograms/kg, i.v.). Only the i.v. administration of methysergide blocked the inhibition induced by i.c. infusion (1.6 micrograms/kg/min) of 5-HT. It is suggested that 5-HT exhibits an inhibitory control on forestomach phasic contractions through hypothalamic and bulbar 5-HT receptors, and exerts peripheral excitatory effects on the tone of the rumen wall.     

Effect of anticholinergic drugs on the electrical activity of the antrum and duodeno-jejunum in sheep

The changes induced in the electrical activity of the small intestine by atropine sulphate, diphemanil methylsulphate, hyoscine butylbromide and prifinium bromide were studied in conscious sheep fitted with chronically implanted electrodes. Increased spike potential activity was induced by carbachol. The mean slow-wave frequency of the antrum was 7.35 ± 0.18/min with burst of spike potentials randomly superimposed on about 63% of the slow waves. The occurrence of the spike bursts was inhibited for 18—30 min after an intravenous injection of atropine (0.75 mg/kg) and during its infusion at the rate of 0.05 mg/kg/min. The activity of the proximal part of the small intestine, which is characterized by migrating myoelectric complexes moving down slowly at hourly intervals, was replaced by irregular series consisting of spike bursts of about 3 min duration, at intervals of about 12 min for a total of 110 min. Such an effect, in which the level of spike activity was reduced, was also observed with hyoscine, diphemanil and prifinium during 80, 120 and 180 min periods respectively. The injection of carbachol was followed by continuous spike activity in which the mean spike level was nearly doubled, as occurs at the onset of diarrhoea. An inhibitory effect was observed at both antral and duodeno-jejunal levels with the four drugs used, that of hyoscine being least marked. The effect of prifinium was more pronounced than that of atropine or diphemanil, especially on the jejunum. The results suggest that the ability of these drugs to reduce the level of spike activity accompanying disruption of migrating myoelectric complexes and to inhibit the carbachol-induced increased level of spiking may account for the antispasmodic effects observed after the use of anticholinergic drugs in gastrointestinal disorders. Prifinium had the longest lasting effect at both antral and duodeno-jejunal levels and seemed to be a good atropine substitute to alleviate gastro-intestinal hypermotility.     

Relative oxytocic properties of fenprostalene compared with cloprostenol, prostaglandin F2 alpha, and oxytocin in the ovariectomized ewe

The oxytocic effect of a prostaglandin F2 alpha analogue, fenprostalene, was assessed in 4 ovariectomized ewes fitted with electrodes in both uterine horns and in the cervix. In the absence of estradiol priming, significant motility changes were not elicited by fenprostalene. Conversely, when ewes were primed with 17-beta-estradiol, fenprostalene markedly increased the electrical activity in the uterus and cervix. After a single subcutaneous fenprostalene administration (5 micrograms/kg), activity values remained about twice that of the control values during 8.52 +/- 3.31 hours. When the same dosage was administered IM, similar post-injection activity values were obtained, but only during 5.88 +/- 0.72 hours. Oxytocic effects of fenprostalene were far longer than those elicited by a single IM administration of 50 micrograms of prostaglandin F2 alpha (tham salt)/kg (0.91 +/- 0.32 hours) or by a single IM administration of 1 microgram of cloprostenol/kg (1.88 +/- 0.81 hours). Using the dose-effect relationship curve obtained from the same ewes by continuous IV infusions of oxytocin (OXT), the postinjection activity values reached after a single subcutaneous administration of fenprostalene were equivalent to those of an IV infusion of OXT at an average dose of 4.09 ImU of OXT/kg/hr for 6 to 13 hours, according to the values of the particular ewe concerned. These long-lasting oxytocic properties, in addition to its luteolytic capabilities, would make fenprostalene a suitable drug for promoting effective evacuation of the uterus when required in daily veterinary practice.     

Effects of fenoldopam on cecal blood flow and mechanical activity in horses

Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity in the duodenum, right ventral colon, cecal body, and cecal apex were measured in 6 conscious healthy horses for 60 minutes during and for 120 minutes after IV infusion of 0.9% NaCl solution (control) or fenoldopam. There were no significant changes in these measurements during or after infusion of 0.9% NaCl (saline) solution. Fenoldopam, a selective dopamine-1 receptor agonist, was administered in saline solution at dosages of 0.01, 0.05, and 0.1 micrograms/kg/min. Intravenous infusion of fenoldopam at 0.01 microgram/kg/min significantly increased heart rate, but did not change average carotid arterial pressure or lateral cecal arterial blood flow. Intravenous infusion of fenoldopam at both 0.05 and 0.1 microgram/kg/min significantly increased heart rate, significantly decreased average carotid arterial pressure, and significantly increased lateral cecal arterial blood flow. Intravenous infusion of fenoldopam at 0.01, 0.05, and 0.1 microgram/kg/min did not significantly change the mechanical activity measured by the area under the strain gauge deflection curve for the duodenum, right ventral colon, cecal body, or cecal apex. These results suggest that dopaminergic-1 receptors are present on the colonic vasculature of horses. There was no evidence, however, that dopaminergic-1 receptors exist on the visceral smooth muscle of the duodenum, right ventral colon, cecal body, or cecal apex of horses.     

Antinociceptive actions of intravenous a2-adrenoceptor agonists in sheep

The antinociceptive activity of the intravenously administered alpha 2-adrenoceptor agonists, clonidine and xylazine, was measured in sheep using thermal and mechanical pressure threshold detection systems. Both drugs demonstrated clear antinociceptive activity for both forms of threshold stimuli and clonidine at 6 micrograms/kg i.v. was more potent and longer lasting than xylazine at 50 micrograms/kg i.v. The antinociceptive effects were reversed by idazoxan (0.1 mg/kg i.v.), but were not affected by naloxone at 0.2 mg/kg i.v. indicating that these effects were mediated by alpha 2-adrenoceptors.     

Effects of dopamine administration on cecal mechanical activity and cecal blood flow in conscious healthy horses

Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity of the circular and longitudinal muscle layers of the cecal body were measured in 7 conscious healthy horses during IV infusion of physiologic saline solution for 60 minutes (control), during a 60-minute IV infusion of dopamine (at dosages of 1, 2.5, and 5 micrograms/kg/min), and for 60 minutes after IV infusion of dopamine. The mean values for lateral cecal arterial blood flow during IV infusion of dopamine at a dosage of either 1 or 2.5 micrograms/kg/min were not significantly different from the mean values for lateral cecal arterial blood flow during IV infusion of saline solution. The mean values for lateral cecal arterial blood flow, however, were significantly greater during IV infusion of dopamine at a dosage of 5 micrograms/kg/min than the mean values for lateral cecal arterial blood flow during IV infusion of saline solution. Intravenous infusion of dopamine at 1 and 2.5 micrograms/kg/min did not significantly change the mean values for carotid arterial pressure. In contrast, the mean values for carotid arterial pressure were significantly less during IV infusion of dopamine at dosages of 2.5 and 5 micrograms/kg/min than during infusion of saline solution. The mean values for heart rate were not significantly altered by infusion of dopamine at a dosage of either 1 or 2.5 micrograms/kg/min, but infusion of dopamine at a dosage of 5 micrograms/kg/min significantly increased heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of remifentanil infusion regimens on cardiovascular function and responses to noxious stimulation in propofol-anesthetized cats

OBJECTIVE: To evaluate the effects of 2 remifentanil infusion regimens on cardiovascular function and responses to nociceptive stimulation in propofol-anesthetized cats. ANIMALS: 8 adult cats. PROCEDURES: On 2 occasions, cats received acepromazine followed by propofol (6 mg/kg then 0.3 mg/kg/min, i.v.) and a constant rate infusion (CRI) of remifentanil (0.2 or 0.3 microg/kg/ min, i.v.) for 90 minutes and underwent mechanical ventilation (phase I). After recording physiologic variables, an electrical stimulus (50 V; 50 Hz; 10 milliseconds) was applied to a forelimb to assess motor responses to nociceptive stimulation. After an interval (> or = 10 days), the same cats were anesthetized via administration of acepromazine and a similar infusion regimen of propofol; the remifentanil infusion rate adjustments that were required to inhibit cardiovascular responses to ovariohysterectomy were recorded (phase II). RESULTS: In phase I, heart rate and arterial pressure did not differ between remifentanil-treated groups. From 30 to 90 minutes, cats receiving 0.3 microg of remifentanil/kg/min had no response to noxious stimulation. Purposeful movement was detected more frequently in cats receiving 0.2 microg of remifentanil/kg/min. In phase II, the highest dosage (mean +/- SEM) of remifentanil that prevented cardiovascular responses was 0.23 +/- 0.01 microg/kg/min. For all experiments, mean time from infusion cessation until standing ranged from 115 to 140 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Although the lower infusion rate of remifentanil allowed ovariohysterectomy to be performed, a CRI of 0.3 microg/kg/min was necessary to prevent motor response to electrical stimulation in propofol-anesthetized cats. Recovery from anesthesia was prolonged with this technique.     

Parasympathetic influence on the arrhythmogenicity of graded dobutamine infusions in halothane-anesthetized horses.

We investigated the influence of parasympathetic tone on the arrhythmogenicity of graded dobutamine infusions in horses anesthetized under clinical conditions. Six horses were used in 9 trials. Two consecutive series of graded dobutamine infusions were given IV; each continuous graded dobutamine infusion was administered for 20 minutes. The dobutamine infusion dosage (5, 10, 15, and 20 micrograms/kg of body weight/min) was increased at 5-minute intervals. Isovolumetric saline solution vehicle (v) or atropine (A; 0.04 mg/kg) was administered IV, or bilateral vagotomy (VG) was performed as a treatment before the second series of dobutamine infusions. Treatment was not administered prior to the first dobutamine infusion. Significant interaction between treatment and dosage of dobutamine infusion existed for differences from baseline for mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, heart rate, and cardiac index at dosages of 5 and 10 micrograms of dobutamine/kg/min, given IV and for heart rate at dosage of 15 micrograms of dobutamine/kg/min, given IV. Results for group-V horses were different from those for group-A and group-VG horses, but were not different between group-A and group-VG horses in all aforementioned cases, except for heart rate and cardiac index at dosage of 5 micrograms of dobutamine/kg/min, given IV. Normal sinus rhythm, second-degree atrioventricular block, and bradyarrhythmias predominated during low dobutamine infusion rates during the first infusion series (nontreated horses) and in group-V horses during the second infusion series. Only tachyarrhythmias were observed during the second infusion series in the horses of the A and VG groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biphasic disruption of fasting equine gut motility by dopamine – a preliminary study

Dopamine was infused intravenously (1, 5 and 10 micrograms/kg/min) for 60 min in three fasted ponies. A dose-dependent increase in heart rate occurred that was rapid in onset and termination at the start and end of the infusions, respectively. Dose-dependent changes in gastric and small intestinal motility were observed. An initial marked inhibition of gastric contraction amplitude was followed by a secondary prolonged period of activity. At the same time the small intestine showed a prolonged period of irregular activity (phase II) and a marked increase in the interval between successive phase IIIs. The left dorsal colon and small colon exhibited variable responses. The normal fasting motility pattern was therefore disrupted by dopamine biphasically, an initial inhibition of the stomach being followed by a period of increased activity in the stomach and small intestine which resembled the postprandial motility pattern. Although the cardiovascular effects of dopamine were transient, the increases in gastrointestinal motility persisted long after the infusion was terminated.     

Arrhythmogenicity of dopamine and its effects on hemodynamics in dogs under halothane anesthesia

The arrhythmogenicity of dopamine, its effects on cardiac function, hemodynamics, and diuresis under halothane anesthesia were evaluated in dogs. The induction time of arrhythemias and the effect of arrhythmias on cardiac function, hemodynamics, and diuresis were determined after infusion of dopamine for 30-min period at increasing doses of 3, 5, 7, 10, and 15 micrograms/kg/min. The results were as follows. 1. Arrhythmia induction percentage was 28.6% at 5 micrograms/kg/mn, 42.9% at 7 micrograms/kg/min, 25% at 10 micrograms/kg/min, and 41.7% at 15 micrograms/kg/min. The induction time of arrhythemias (sec) was 459 at 5 micrograms/kg/min, 332 at 7 micrograms/kg/min, 152 at 10 micrograms/kg/min, and 279 at 15 micrograms/kg/min. No arrhythmias were present at 3 micrograms/kg/min. 2. Heart rate and myocardial oxygen consumption was increased in the arrhythmia-induced group compared to the non-arrhythmia-induced group. 3. Myocardial contractility, mean aortic pressure, mean pulmonary arterial pressure, and diuresis increased dose-dependently in the non-arrhythmia-induced group; however, these measures were increased in the arrhythmia-induced group without regard to dose.     

Effect of verapamil on cardiac chronotropic response to vagal stimulation in neonatal pigs

The effects of verapamil on the chronotropic response to vagal stimulation in young pigs anesthetized with sodium pentobarbital (30 mg/kg of body weight, intraperitoneally) was evaluated. After bilateral vagotomy, the administration of verapamil (loading dose of 100 micrograms/kg, followed by 2 micrograms/kg/min infusion) resulted in a significant (P less than 0.05) reduction in heart rate (HR) and mean arterial blood pressure. Cardiac frequency responses to vagal stimulation were obtained by stimulating the distal end of the right vagus nerve at selected frequencies (5, 10, 15, and 20 Hz) with supramaximal voltage (10 to 15 V) and constant duration (2 ms). The HR was measured after 15 s at each level of stimulation. The slopes of decrease in HR to the frequency of vagal stimulation were significantly (P less than 0.05) reduced after verapamil as compared with its controls. After atropine (0.5 mg/kg), the vagally induced tachycardia was partially attenuated by verapamil, but was completely eliminated by beta blockade with propranolol (1 mg/kg). These findings indicated that verapamil may influence the parasympathetic control of the heart in young pigs.     

Effects of medetomidine on intestinal and colonic motility in the dog

The motor responses of the jejunum and colon to stimulation of α₂-adrenoceptors by medetomidine and clonidine were investigated in four dogs. In fasting dogs, medetomidine, at a dose rate of 30 μg/kg i.v., disrupted the migrating myoelectric complex (MMC) pattern of the small intestine for about 2 h. Similar, but shorter-lasting effects were also induced by clonidine (30 μg/kg i.v.) on the jejunum. The administration of α₂-agonists inhibited colonic motility in fasting dogs, although medetomidine-induced inhibition was preceded by a short period of increased muscle tone. All these effects were reversed by the α₂-antagonists atipamezole (0.15 mg/kg i.v.) and yohimbine (0.20 mg/kg i.v.). In fed dogs, medetomidine (30 μg/kg i.v.) induced a strong increase of the tone on the proximal colon, while the activity of the medium and distal colon was completely suppressed. Yohimbine (0.50 mg/kg i.v.) immediately restored the activity of the colon and induced a propagated giant contraction and defaecation by the animal. These data confirm the importance of a₂-adrenergic receptors in the control of intestinal and colonic motility in the dog.     

Medetomidine- and medetomidine-ketamine-induced immobilization in blue foxes (Alopex lagopus) and its reversal by atipamezole

The sedative and immobilizing effects of the alpha 2-adrenoceptor agonist medetomidine alone or combined with the dissociative anesthetic ketamine, were studied in blue foxes. Medetomidine at doses of 25 and 50 micrograms/kg induced moderate to deep sedation, but only with the highest medetomidine dose tested, 100 micrograms/kg, was the immobilization complete. Medetomidine 50 micrograms/kg combined with ketamine 2.5 mg/kg rapidly induced complete immobilization, characterized by good myorelaxation, and no clinically significant alterations in serially determined hematologic and serum chemistry parameters. The alpha 2-adrenoceptor antagonist atipamezole effectively reversed the medetomidine- or medetomidine-ketamine-induced immobilizations. A transient increase in heart rates was noted after each atipamezole injection.     

Medetomidine-ketamine anaesthesia induction followed by medetomidine-propofol in ponies: infusion rates and cardiopulmonary side effects

REASONS FOR PERFORMING STUDY: To search for long-term total i.v. anaesthesia techniques as a potential alternative to inhalation anaesthesia. OBJECTIVES: To determine cardiopulmonary effects and anaesthesia quality of medetomidine-ketamine anaesthesia induction followed by 4 h of medetomidine-propofol anaesthesia in 6 ponies. METHODS: Sedation consisted of 7 microg/kg bwt medetomidine i.v. followed after 10 min by 2 mg/kg bwt i.v. ketamine. Anaesthesia was maintained for 4 h with 3.5 microg/kg bwt/h medetomidine and propofol at minimum infusion dose rates determined by application of supramaximal electrical pain stimuli. Ventilation was spontaneous (F(I)O2 > 0.9). Cardiopulmonary measurements were always taken before electrical stimulation, 15 mins after anaesthesia induction and at 25 min intervals. RESULTS: Anaesthesia induction was excellent and movements after pain stimuli were subsequently gentle. Mean propofol infusion rates were 0.89-0.1 mg/kg bwt/min. No changes in cardiopulmonary variables occured over time. Range of mean values recorded was: respiratory rate 13.0-15.8 breaths/min; PaO2 29.1-37.9 kPa; PaCO2 6.2-6.9 kPa; heart rate 31.2-40.8 beats/min; mean arterial pressure 90.0-120.8 mmHg; cardiac index 44.1-59.8 ml/kg bwt/min; mean pulmonary arterial pressure 11.8-16.4 mmHg. Recovery to standing was an average of 31.1 mins and ponies stood within one or 2 attempts. CONCLUSIONS: In this paper, ketamine anaesthesia induction avoided the problems encountered previously with propofol. Cardiovascular function was remarkably stable. Hypoxaemia did not occur but, despite F(I)O2 of > 0.9, minimal PaO2 in one pony after 4 h anaesthesia was 8.5 kPa. POTENTIAL RELEVANCE: The described regime might offer a good, practicable alternative to inhalation anaesthesia and has potential for reducing the fatality rate in horses.     

Effects of the opioid remifentanil on the arrhythmogenicity of epinephrine in halothane-anesthetized dogs

Opioids may exert a protective effect against ventricular arrhythmias via a vagally mediated mechanism. This study evaluated the effects of the opioid remifentanil on arrhythmogenicity of epinephrine during halothane anesthesia. Eight dogs were assigned to 2 treatments in a randomized crossover design, with 1-week intervals between treatments. Anesthesia was maintained with 1.3% end-tidal halothane in oxygen and mechanical ventilation to maintain eucapnia. A constant rate infusion of remifentanil (0.72 microg/kg/min) was administered throughout the study in the experimental treatment, while control animals received physiologic saline as placebo. The arrhythmogenic dose of epinephrine (ADE), defined as 4 premature ventricular complexes (PVCs) within 15 s, was determined by administering progressively increasing infusion rates of epinephrine (2.5, 5.0, and 10 microg/kg/min), allowing 20 min intervals between each infusion rate. In both treatments, epinephrine infusions induced bradyarrhythmias and atrioventricular conduction disturbances, which were followed by escape beats and PVCs. In the remifentanil treatment, mean +/- s ADE values (11.3 +/- 4.9 microg/kg) did not differ from values observed in control animals (9.9 +/- 6.1 microg/kg). On the basis of the ADE model for assessing the arrhythmogenity of drugs during halothane anesthesia, the present study did not demonstrate a protective effect of remifentanil (0.72 microg/kg/min) against ventricular arrhythmias in dogs.