Cardiovascular and hepatic responses of rhesus macaques to staphylococcal enterotoxin B.

Certain cardiovascular and hepatic functions were measured for a period of 6 to 14 hours in conscious, chaired, male rhesus macaques given (intravenously (IV) or orally) staphylococcal enterotoxin B (SEB). In macaques orally given SEB (1 mg/kg), there was little change in the cardiovascular variables. The half-life of injected indocyanine green was apparently prolonged in macaques given SEB as compared with that in the controls. However, in macaques given SEB (0.05 or 1.0 mg/kg) by IV injection, there were tachycardia, increase in arterial resistance, and decreases in blood pressure, cardiac output, stroke volume, cardiac work, mean cardiac power, and central blood volume. In addition, mean transit time from caudal vena cava to ascending aorta was prolonged and a simultaneous reduction of hepatic removal of indocyanine green occurred.     

Effect of staphylococcal enterotoxin B on cardiorenal functions and survival in X-irradiated rhesus macaques.

Pretreatment of rhesus macaques with nonlethal total-body x-irradiation (400 R) prolonged survival time from an average of 15 hours to 101 hours after intravenous (IV) inoculation of 50 microgram of staphylococcal enterotoxin B (SEB)/kg of body weight. Radiation exposure per se did not produce detectable cardiorenal changes; however, the longer survival after SEB challenge exposure in x-irradiated rhesus macaques was associated with improved cardiorenal functions if compared with that of nonirradiated macaques given the same dose of SEB. Total-body radiation exposure 4 days prior to IV SEB inoculation prevented typical SEB-induced decreases (where measured at 5 hours) in cardiac output, stroke volume, TcH2O, CPAH, Cosm, and urine flow, as well as increases in total peripheral and renal resistance. A theory concerning the significance of radiation-induced leukopenia on modification of SEB-induced cardiorenal functions is postulated.     

Influence of preinduction methoxamine, lactated Ringer solution, or hypertonic saline solution infusion or postinduction dobutamine infusion on anesthetic-induced hypotension in horses

A controlled study of the cardiovascular responses in horses anesthetized with acepromazine (0.05 mg/kg of body weight, IV), guaifenesin (100 mg/kg, IV), thiamylal (5.0 mg/kg, IV), and halothane in O2 (1.2 to 1.4% end-expired concentration) was performed to determine whether hypotension could be prevented by use of various treatments. Six horses were given 5 treatments in a randomized sequence: no treatment (control), methoxamine (0.04 mg/kg, IV), lactated Ringer solution (20.0 ml/kg, IV), 7.5% hypertonic saline solution (4.0 ml/kg, IV), or constant infusion of dobutamine (5.0 mg/kg/min, IV) during anesthesia. Heart rate, ECG, blood pressure, central venous pressure, cardiac output, blood gas analysis, PVC, and plasma total protein concentration were measured during the study. Compared with the control value, an increase in blood pressure during halothane administration was observed after administration of lactated Ringer solution, hypertonic saline solution, or dobutamine (P less than 0.05). The improved blood pressure response to hypertonic saline solution and dobutamine was related to an increase in cardiac output, which was statistically significant (P less than 0.05). Other statistically significant differences in cardiopulmonary responses among treatments were not observed during anesthesia. The PCV was increased in response to dobutamine infusion, and plasma total protein concentration was reduced in response to administration of hypertonic saline or lactated Ringer solution.     

Comparison of the cardiopulmonary effects of etomidate and thiamylal in dogs.

The cardiopulmonary effects of etomidate, a nonbarbiturate, short-acting, IV anesthetic, were compared and contrasted with those of thiamylal sodium in chronically instrumented conscious dogs. Etomidate, when administered IV at dosages of 1.5 and 3.0 mg/kg of body weight, produced anesthesia lasting from 8 +/- 5 and 21 +/- 9 minutes, respectively. Heart rate, aortic blood pressure, left ventricular peak pressure, left ventricular end diastolic pressure, left ventricular contractile force, and myocardial oxygen consumption were unchanged after administration of either dose of etomidate; however, the dosage of 1.5 mg/kg produced significant (P less than 0.05) increases in respiratory rate and decreases in tidal volume. The minute volume remained unchanged from base-line values. Significant (P less than 0.05) decreases in tidal volume, arterial pH, and partial pressure of oxygen were produced, and minute volume remained unchanged when 3.0 mg of etomidate/kg of body weight was administered. Thiamylal sodium (8.0 mg/kg of body weight; given IV) produced anesthesia lasting for 14 +/- 5 minutes. Significant increases (P less than 0.05) in heart rate, arterial blood pressure, left ventricular peak pressure, and myocardial oxygen consumption were observed after IV administration. Left ventricular contractility was significantly (P less than 0.05) decreased. Respiratory rate was not significantly (P less than 0.05) affected by thiamylal although tidal volume and minute volume were decreased. These respiratory alterations resulted in significant (P less than 0.05) increases in the arterial partial pressure of carbon dioxide and decreases in pH and the partial pressure of oxygen. On the basis of cardiopulmonary function, etomidate offered rapid, safe, short duration anesthesia superior to that of thiamylal sodium.     

The effects on cardio-respiratory and acid-base variables of the anaesthetic alfaxalone in a 2-hydroxypropyl-β-cyclodextrin (HPCD) formulation in sheep

The objective of this study was to determine the pharmacodynamic effects in sheep of the anaesthetic alfaxalone in a 2-hydroxypropyl-β-cyclodextrin formulation. Seven Ripollesa sheep, weighing 43.0±6.6 kg, were used in the study. Twenty-four hours after instrumentation, the sheep were anesthetised with alfaxalone (2 mg/kg bodyweight IV) in cyclodextrin. Heart rate, arterial blood pressure, respiratory rate and arterial blood gases were recorded. Alfaxalone administration resulted in minimal cardio-respiratory depression. Time to standing from anaesthesia was 22.0±10.6 min. Apnoea was not observed in any of the sheep. Significant differences from baseline were not observed in respiratory rate or arterial blood pressure. Heart rate increased significantly (P<0.05) immediately after administration, returning to control values at 20 min. The calculated haemoglobin saturation (SO2) decreased significantly during the first 15 min after alfaxalone administration. The arterial pH decreased significantly during the first 30 min of the study, although no significant differences from basal values were observed in the arterial partial pressure of carbon dioxide (PaCO2). The results showed that alfaxalone in 2-hydroxypropyl-β-cyclodextrin administered as an IV bolus at 2 mg/kg produced minimal adverse effects and an uneventful recovery from anaesthesia in sheep.     

Evaluation of Pentobarbital as a Drug for Standing Sedation in Cattle

Pentobarbital (1.0, 1.5, and 2.0 mg/kg intravenously [IV]) was administered to four adult cows to determine a dose suitable for producing standing sedation in adult cattle, and to evaluate its effects on cardiopulmonary function and rumen motility. The response was assessed after 15, 30, 60, and 90 minutes. The 1.0 and 1.5 mg/kg doses induced mild sedation at 15 and 30 minutes, and no sedation at 60 and 90 minutes. The 2.0 mg/kg dose produced moderate sedation at 15 and 30 minutes, and mild sedation at 60 minutes. The 2.0 mg/kg dose was judged to be the most suitable. The effects of pentobarbital (2.0 mg/kg IV) on heart rate, blood pressure, respiratory rate, blood gases, and rumen motility were measured in five cows during a 90 minute period. Respiratory rate was significantly depressed at 15, 30, and 60 minutes, but there were no significant changes in the other variables. Pentobarbital (2.0 mg/kg IV) is reliable in adult cattle for standing sedation of short duration.     

Cardiopulmonary effects of a medetomidine-ketamine combination administered intravenously in gopher tortoises

OBJECTIVE: To determine whether IV administration of a combination of medetomidine and ketamine depresses cardiopulmonary function in healthy adult gopher tortoises. DESIGN: Prospective study. ANIMALS: 3 adult male and 3 adult female nonreleasable gopher tortoises. PROCEDURE: Prior to the study, carotid and jugular catheters were surgically placed in each tortoise for blood collection, direct arterial blood pressure monitoring, and drug administration. Heart rate, direct carotid arterial blood pressure, and body temperature were measured before and every 5 minutes for 45 minutes after IV injection of medetomidine (100 microg/kg [45.5 microg/lb]) and ketamine (5 mg/kg [2.3 mg/lb]). Carotid arterial blood samples were collected before and 5, 15, 30, and 45 minutes after medetomidine-ketamine administration to determine pH, PO2, and PCO2. Atipamezole (500 mg/kg [227 microg/lb], IV) was administered 30 minutes after administration of medetomidine-ketamine. RESULTS: The medetomidine-ketamine combination caused a moderate increase in arterial blood pressure, and moderate hypercapnia and hypoxemia. There were no significant changes in heart rate or body temperature. Intravenous administration of atipamezole rapidly induced severe hypotension. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of medetomidine and ketamine administered IV resulted in effective short-term immobilization adequate for minor diagnostic procedures in gopher tortoises. This combination also caused moderate hypoventilation, and it is recommended that a supplemental source of oxygen or assisted ventilation be provided. Atipamezole administration hastens recovery from chemical immobilization but induces severe hypotension. It is recommended that atipamezole not be administered IV for reversal of medetomidine in tortoises and turtles.     

Alterations in epinephrine-induced arrhythmogenesis after xylazine and subsequent yohimbine administration in isoflurane-anesthetized dogs

Effects of xylazine (1.1 mg/kg of body weight, IV bolus, plus 1.1 mg/kg/h infusion) and subsequent yohimbine (0.125 mg/kg, IV bolus) administration on the arrhythmogenic dose of epinephrine (ADE) in isoflurane (1.8% end-tidal)-anesthetized dogs were evaluated. The ADE was defined as the total dose of epinephrine that induced greater than or equal to 4 premature ventricular contractions within 15 seconds during a 3-minute infusion period or within 1 minute after the end of infusion. Total ADE values during isoflurane anesthesia, after xylazine administration, and after yohimbine injection were 36.6 +/- 8.45 micrograms/kg, 24.1 +/- 6.10 micrograms/kg, and 45.7 +/- 6.19 micrograms/kg, respectively. Intravenous xylazine administration significantly (P less than 0.05) increased blood pressure and decreased heart rate, whereas yohimbine administration induced a significant (P less than 0.05) decrease in blood pressure. induced a significant (P less than 0.05) decrease in blood pressure. After yohimbine administration, the ADE significantly (P less than 0.05) increased above that after isoflurane plus xylazine administration. After yohimbine administration, blood pressure measured immediately before epinephrine-induced arrhythmia was significantly (P less than 0.05) less than the value recorded during isoflurane plus xylazine anesthesia. Heart rate was unchanged among treatments immediately before epinephrine-induced arrhythmia. Seemingly, yohimbine possessed a protective action against catecholamine-induced arrhythmias in dogs anesthetized with isoflurane and xylazine.     

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.     

Sedative and analgesic effects of intravenous xylazine and tramadol on horses

This study was performed to evaluate the sedative and analgesic effects of xylazine (X) and tramadol (T) intravenously (IV) administered to horses. Six thoroughbred saddle horses each received X (1.0 mg/kg), T (2.0 mg/kg), and a combination of XT (1.0 and 2.0 mg/kg, respectively) IV. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), indirect arterial pressure (IAP), capillary refill time (CRT), sedation, and analgesia (using electrical stimulation and pinprick) were measured before and after drug administration. HR and RR significantly decreased from basal values with X and XT treatments, and significantly increased with T treatment (p < 0.05). RT and IAP also significantly increased with T treatment (p < 0.05). CRT did not change significantly with any treatments. The onset of sedation and analgesia were approximately 5 min after both X and XT treatments; however, the XT combination produced a longer duration of sedation and analgesia than X alone. Two horses in the XT treatment group displayed excited transient behavior within 5 min of drug administration. The results suggest that the XT combination is useful for sedation and analgesia in horses. However, careful monitoring for excited behavior shortly after administration is recommended.     

Cardiovascular and pharmacokinetic effects of isoxsuprine in the horse

Isoxsuprine (0.6 mg/kg) administered IV to 6 standing horses produced substantial, transient decreases in systemic blood pressure, systemic vascular resistance, and stroke volume. It also produced substantial, transient increases in heart rate, cardiac output, and purposeful movement. Plasma concentrations of isoxsuprine peaked soon after the drug was administered IV and then decreased over a 12-hour period in a biexponential manner, with distribution and elimination half-lives of 14 minutes and 2.67 hours, respectively. Total body clearance and steady-state volume of distribution were calculated to be 53.8 ml/min/kg and 10.5 L/kg, respectively. When a recommended therapeutic dosage regimen (0.6 mg/kg 2 times a day, per os) was used in 4 of these horses, changes were not detected. Isoxsuprine was not detected in plasma after the drug was given orally. We conclude that 0.6 mg of isoxsuprine/kg given orally every 12 hours is not likely to produce cardiovascular changes in the resting horse and that this is probably because plasma concentrations are not high enough to do so.     

Doxapram: cardiopulmonary effects in the horse

The cardiopulmonary effects of 3 dosages of doxapram hydrochloride (0.275 mg/kg, 0.55 mg/kg, and 1.1 mg/kg, IV) were studied in 6 adult horses. Doxapram given IV significantly (P less than 0.05) decreased PaCO2 and increased respiratory rate, cardiac output arterial blood pressures (systolic, mean, and diastolic) arterial pH, and PaO2 at 1 minute after each dose was administered. Heart rate and mean and diastolic pulmonary arterial blood pressure were significantly (P less than 0.05) increased 1 minute after the 2 larger dosages of doxapram were given (0.55 mg/kg and 1.1 mg/kg, IV), but not after the smallest dosage was given. All measurements, except heart rate and cardiac output, had returned to base line by 5 minutes after each dosing. Heart rate remained significantly (P less than 0.05) increased 10 minutes after the 0.55 mg/kg dosage was given and 30 minutes after the 1.1 mg/kg dosage. Cardiac output remained significantly (P less than 0.05) increased at 10 minutes, 5 minutes, and 30 minutes after the 0.275, 0.55, and 1.1 mg/kg dosages, respectively, were given.     

Xylazine and tiletamine-zolazepam anesthesia in horses

The cardiopulmonary and anesthetic effects of xylazine in combination with a 1:1 mixture of tiletamine and zolazepam were determined in 6 horses. Each horse was given xylazine IV or IM, as well as tiletamine-zolazepam IV on 4 randomized occasions. Anesthetics were administered at the rate of 1.1 mg of xylazine/kg of body weight, IV, 1.1 mg of tiletamine-zolazepam/kg, IV (treatment 1); 1.1 mg of xylazine/kg, IV, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 2); 1.1 mg of xylazine/kg, IV, 2.2 mg of tiletamine-zolazepam/kg, IV (treatment 3); and 2.2 mg of xylazine/kg, IM, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 4). Tiletamine-zolazepam doses were the sum of tiletamine plus zolazepam. Xylazine, when given IV, was given 5 minutes before tiletamine-zolazepam. Xylazine, when given IM, was given 10 minutes before tiletamine-zolazepam. Tiletamine-zolazepam induced recumbency in all horses. Duration of recumbency in group 1 was 31.9 +/- 7.2 (mean +/- 1 SD) minutes. Increasing the dosage of tiletamine-zolazepam (treatments 2 and 3) significantly (P less than 0.05) increased the duration of recumbency. Xylazine caused significant (P less than 0.05) decreases in heart rate and cardiac output and significant (P less than 0.05) increases in central venous pressure and mean pulmonary artery pressure 5 minutes after administration. Respiratory rate was decreased. Arterial blood pressures increased significantly (P less than 0.05) after xylazine was administered IV in treatments 1 and 3, but the increases were not significant in treatment 2. Xylazine administered IM caused significant (P less than 0.05) increases in central venous pressure and significant (P less than 0.05) decreases in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxymorphone: cardiovascular, pulmonary, and behavioral effects in dogs

Cardiovascular, pulmonary, and behavioral effects of multiple doses of oxymorphone in 10 nonanesthetized, spontaneously breathing, healthy dogs were studied. Oxymorphone (0.4 mg/kg of body weight) was administered IV, and at 20, 40, and 60 minutes after the first injection was given, 0.2 mg of oxymorphone/kg was administered. Cardiovascular and pulmonary variables were measured before (base line) and at 5, 15, 35, 55, 75, 100, 120, 150, 180, 210, 240, 270, and 300 minutes after the first oxymorphone injection. Degree of sedation and behavioral effects also were recorded. Naloxone (0.04 mg/kg, IV) was administered 4.5 hours after the 4th oxymorphone injection, and behavioral changes were recorded. Oxymorphone induced mild respiratory depression. After transient apnea developed, respiratory rate increased to a pant, tidal volume decreased, and minute ventilation increased, but these values were not significantly (P = 0.05) different from base line. The PaCO2, physiologic dead space, and base deficit increased; alveolar tidal volume decreased; and alveolar minute ventilation did not change. The PaO2 decreased, hemoglobin and arterial O2 content increased, and O2 transport did not change. Venous admixture transiently increased. Oxymorphone induced minimal cardiovascular depression. Mean arterial blood pressure, stroke volume, central venous pressure, pulmonary artery pressure, and pulmonary wedge pressure increased. Heart rate decreased, systemic vascular resistance transiently increased, and cardiac output transiently decreased. Because the dogs moved spontaneously, responded to sound with sudden, vigorous movements, and breathed with excessive effort, oxymorphone alone was considered inadequate as a general anesthetic.     

The effect of hyoscine on dobutamine requirement in spontaneously breathing horses anaesthetized with halothane

OBJECTIVE: To determine whether hyoscine has a sparing effect on the volume of dobutamine required to maintain mean arterial pressure (MAP) at 70 mmHg in horses anaesthetized with halothane. STUDY DESIGN: Prospective, randomized, controlled clinical trial. ANIMALS: Twenty adult horses weighing 507 +/- 97 kg (mean +/- SD), aged 10 +/- 5 years. MATERIALS AND METHODS: Pre-anaesthetic medication in all horses was intramuscular (IM) acepromazine (40 mug kg(-1)) and intravenous (IV) detomidine (0.02 mg kg(-1)). Anaesthesia was induced with ketamine (2.2 mg kg(-1) IV) and diazepam (0.02 mg kg(-1) IV), and maintained with halothane in oxygen. Horses breathed spontaneously. Flunixin (1.1 mg kg(-1) IV) was given to provide analgesia. Heart rate, ECG, invasive arterial pressure, respiratory rate, percentage end-tidal carbon dioxide, percentage end-tidal halothane and partial pressure of oxygen and carbon dioxide in arterial blood and blood pH were monitored. Dobutamine was infused by an infusion pump to maintain MAP at 70 mmHg. Horses were randomly assigned to receive saline or hyoscine (0.1 mg kg(-1)) IV 30 minutes after induction. The heart rate, MAP and volume of dobutamine infused over 30-minute periods were measured and analysed statistically using a one-way anova. RESULTS: After administration of hyoscine, heart rate increased for 10 minutes (p < 0.01) and MAP for 5 minutes (p < 0.01). There was no difference in the volume of dobutamine infused over 30 minutes between horses given hyoscine or saline, although there was a wide individual variation in dobutamine requirements. No side effects of hyoscine were seen. CONCLUSIONS: The increase in heart rate and blood pressure that occurs after 0.1 mg kg(-1) hyoscine is given IV in anaesthetized horses, is of short duration and does not significantly alter the amount of dobutamine required to maintain arterial pressure over the next 30 minutes. Clinical relevance The short duration of action of 0.1 mg kg(-1) hyoscine IV may limit its usefulness for correction of hypotension in horses anaesthetized with halothane. Further work is necessary to investigate the effects of higher or repeated doses or constant rate infusions of hyoscine.     

Effects of xylazine on cecal mechanical activity and cecal blood flow in healthy horses

Mechanical activity of the cecal body, lateral cecal arterial blood flow, carotid arterial pressure, and heart rate were measured in 6 conscious healthy horses 30 minutes before and for 120 minutes after IV administration of xylazine at dosages of 1.1 mg/kg of body weight, 0.55 mg/kg, and 0.275 mg/kg. Xylazine at a dosage of 1.1 mg/kg reduced the mean motility index (the product of the mean amplitude of contractions and the total duration of contractile activity divided by the recording time) of the circular and longitudinal muscle layers for the first, second, third, and fourth 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.55 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first and second 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.275 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first 30-minute period after administration of xylazine. Mean lateral cecal arterial blood flow was significantly (P less than 0.05) lower than the base-line value at 2 and 4 minutes after administration of all 3 xylazine dosages and at 8 minutes after administration of xylazine dosages of 1.1 mg/kg and 0.55 mg/kg. All dosages of xylazine caused transient hypertension and bradycardia, followed by hypotension.     

Effects of various antidotal treatments on acetaminophen toxicosis and biotransformation in cats

Oral N-acetylcysteine (NAC), IV NAC, and IV sodium sulfate were evaluated as treatments for cats dosed orally with toxic sublethal doses of acetaminophen (APAP). Six cats were given single oral doses of 120 mg of APAP/kg of body weight and the respective antidote at 4.5, 8.5, and 12.5 hours after APAP dosing in 3 separate trials. The cats were given each antidotal treatment in random order with at least 3 weeks separating the individual APAP-treated trials. Clinical signs, plasma APAP half-lives, clinical chemical values, and APAP urinary excretion and metabolites were studied. Results were compared (P less than 0.05) with each other and with those of a control group of 6 cats given identical APAP doses, but given no antidotal treatment. At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemoglobinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate. All the antidotal treatments produced results significantly different from those in the control cats.     

Cardiovascular and pulmonary effects of atropine reversal of oxymorphone-induced bradycardia in dogs.

Oxymorphone was administered intravenously (IV) to 10 dogs (0.4 mg/kg initial dose followed by 0.2 mg/kg three times at 20-minute intervals). Four hours after the last dose of oxymorphone, heart rates were less than 60 bpm in six dogs. After atropine (0.01 mg/kg IV) was administered, heart rate decreased in five dogs and sinus arrhythmia or second degree heart block occurred in four of them. A second injection of atropine (0.01 mg/kg IV) was administered 5 minutes after the first and the heart rates increased to more than 100 bpm in all six dogs. Ten minutes after the second dose of atropine, heart rate, cardiac output, left ventricular minute work, venous admixture, and oxygen transport were significantly increased, whereas stroke volume, central venous pressure, systemic vascular resistance, and oxygen extraction ratio were significantly decreased from pre-atropine values. The PaCO2 increased and the PaO2 decreased but not significantly. The oxymorphone-induced bradycardia did not produce any overtly detrimental effects in these healthy dogs. Atropine reversed the bradycardia and improved measured cardiovascular parameters.     

Cardiovascular and renal effects of carvedilol in dogs with heart failure

To determine the acute effects of carvedilol (beta-blocker) on cardiovascular and renal function and its pharmacokinetics in dogs. Fifteen mature mongrel dogs (7-15 kg) of both sexes were used in these experiments. Eight dogs served as controls, and seven dogs served as iatrogenic mitral regurgitation (MR) experimental animals. Carvedilol (0.2, 0.4, and 0.8 mg/kg, P.O.) was administered, and the blood carvedilol concentration was analyzed by reverse-phase high-performance liquid chromatography. The response to isoproterenol or phenylephrine was also evaluated. Isoproterenol (0.025 microg/kg/min) was infused via the saphenous vein for 5 min, and phenylephrine (5 microg/kg) was injected with carvedilol (0.2, 0.4 mg/kg) or placebo for 4 days. The heart rate and arterial blood pressure were measured, and LV fractional shortening was measured by echocardiography. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous infusion of sodium thiosulfate and sodium para-aminohippurate. Carvedilol (0.2 mg/kg) decreased the heart rate, whereas renal function, arterial blood pressure, and left ventricular contractile function were not affected. Carvedilol (0.4 mg/kg) decreased heart rate, blood pressure, and renal function. The tachycardic response to isoproterenol was significantly diminished for 36 hr by 0.4 mg/kg carvedilol. Carvedilol 0.2 mg/kg inhibited this effect for 24 hr. Thus, it is necessary to titrate the dosage of carvedilol, it should be initiated at less than 0.2 mg/kg and titrated up to 0.4 mg/kg for heart failure dogs.     

A comparison of extradural and intravenous methadone on intraoperative isoflurane and postoperative analgesia requirements in dogs

Objective To compare the effects of intravenous (IV) and extradural (ED) methadone on end‐tidal isoflurane concentration (Fe ′ISO) and postoperative analgesic requirements in dogs undergoing femoro‐tibial joint surgery. Study Design Randomized, blinded, clinical study. Animals Twenty‐four healthy client‐owned dogs undergoing surgical repair of ruptured cruciate ligaments. Methods Dogs were randomly assigned to two groups of 12 animals and received either ED or IV methadone (0.3 mg kg^?1 diluted with saline to 0.2 mL kg^?1). Pre‐anaesthetic medication was IV acepromazine (0.05 mg kg^?1). Anaesthesia was induced with propofol and maintained initially with an Fe ′ISO of 1.0% delivered in oxygen. Methadone was injected with the dogs in sternal recumbency; the observer was unaware of the administration route. At 10 minutes (stimulation 1) and 20 minutes (stimulation 2) after methadone administration pelvic limb reflexes were tested by digit‐clamping. The time at skin incision (stimulation 3), joint‐capsule incision (stimulation 4), tibial tuberosity drilling (stimulation 5), fabellar suturing (stimulation 6) and extracapsular tightening (stimulation 7) were noted. Changes in heart rate (HR) and respiratory rate and arterial blood pressure associated with surgery were recorded along with the corresponding Fe ′ISO. After 20 minutes of anaesthesia, Fe ′ISO was decreased to the minimum required to maintain stable anaesthesia. Immediately after tracheal extubation, 1, 2, 3 and 6 hours postoperatively and on the morning after surgery, the degree of pain present was assessed using a numerical rating scale. The HR, respiratory rates and blood pressure were also recorded at these times. Serum cortisol and blood glucose concentrations were measured before pre‐anaesthetic medication and at each postoperative pain scoring interval except at 1 and 2 hours. Ketoprofen (2 mg kg^?1), carprofen (4 mg kg^?1) or meloxicam (0.2 mg kg^?1) were given by subcutaneous injection whenever pain scoring indicated moderate discomfort was present. Results Controlled ventilation was required in six dogs which stopped breathing after IV methadone. The median Fe ′ISO at stimulus 5 was 1.0% in the IV and 0.83% in the ED group. At stimulus 6, Fe ′ISO was 1.0% in the IV and 0.8% in the ED group; the difference was statistically significant (p ≤ 0.05). There was no significant difference in the duration of postoperative analgesia associated with administration route. Conclusions Extradural methadone significantly reduces the isoflurane requirement compared with IV methadone during femoro‐tibial joint surgery in dogs. Clinical relevance Extradural methadone provides safe and effective pain relief in dogs undergoing cruciate ligament repair.