Neuromuscular and cardiovascular effects of atracurium in isoflurane-anesthetized chickens.

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered to 24 isoflurane-anesthetized domestic chickens. Birds were randomly assigned to 4 groups, and atracurium was administered at dosage of 0.15, 0.25, 0.35 or 0.45 mg/kg of body weight. The time of onset of twitch depression, the amount of maximal twitch depression, and the duration of muscular relaxation were recorded. After return to control twitch height, atracurium was further administered to achieve > 75% twitch depression. When twitch depression reached 75% during noninduced recovery, 0.5 mg of edrophonium/kg was administered to reverse the muscle relaxation. Throughout the experimental period, cardiovascular, arterial blood gas, and acid-base variables were monitored. The effective dosage of atracurium to result in 95% twitch depression in 50% of birds, (ED95/50) was calculated, using probit analysis, to be 0.25 mg/kg, whereas the ED95/95, the dosage of atracurium to result in 95% twitch depression in 95% of birds, was calculated by probit analysis to be 0.46 mg/kg. The total duration of action at dosage of 0.25 mg/kg was 34.5 +/- 5.8 minutes; at the highest dosage (0.45 mg/kg), total duration increased to 47.8 +/- 10.3 minutes. The return to control twitch height was greatly hastened by administration of edrophonium. Small, but statistically significant changes in heart rate and systolic blood pressure, were associated with administration of atracurium and edrophonium. These changes would not be clinically relevant. In this study, atracurium was found to be safe and reliable for induction of muscle relaxation in isoflurane-anesthetized chickens.     

The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane-anesthetized horses

To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental days (P less than 0.05), despite Day 7 cholinesterase activity that was 16% of pre-trichlorfon values. For atracurium Injections 1 and 2-5, 85 and 43 micrograms/kg of atracurium, respectively, were required to produce a 95-99% reduction in hoof twitch. The time from injection to maximum twitch reduction was approximately 9 min after Injection 1 and 5 min after subsequent injections. Time from injection to maximum twitch reduction was significantly longer for Injection 1 than Injections 2-5 on both experimental days. The time from maximum twitch reduction until 10% recovery was approximately 8 min, with no significant difference between experimental days. The time for twitch recovery from 10 to 75% was approximately 17 min for all injections. Antagonism of atracurium with edrophonium caused the twitch height to return to pre-atracurium strength in approximately 7 min. Edrophonium caused a significant increase in arterial blood pressure. Heart rate change was variable after edrophonium.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of intraoperative fentanyl in spontaneously breathing dogs undergoing orthopaedic surgery

Nineteen dogs were assigned randomly to one of three groups. Animals in Group 1 were pre-medicated with acepromazine, 50 μg/kg bodyweight (bwt) intramuscularly (im) and received 10 ml of 0.9 per cent saline intravenously (iv) at the time of skin incision. Dogs in Group 2 were pre-medicated with acepromazine, 50 μg/kg bwt im, and received fentanyl 2 μg/kg bwt iv at skin incision. Dogs in Group 3 were pre-medicated with acepromazine, 50 μg/kg bwt and atropine, 30 to 40 μg/kg bwt, im and received fentanyl, 2 μg/kg bwt iv at skin incision. Pulse rate, mean arterial blood pressure, respiratory rate and end tidal carbon dioxide were measured before and after fentanyl or saline injection. Fentanyl caused a short-lived fall in arterial blood pressure that was significant in dogs premedicated with acepromazine, but not in dogs pre-medicated with acepromazine and atropine. A significant bradycardia was evident for 5 mins in both fentanyl treated groups. The effect on respiratory rate was most pronounced in Group 3, in which four of seven dogs required intermittent positive pressure ventilation (IPPV) for up to 14 mins. Two of six dogs in Group 2 required IPPV, whereas respiratory rate remained unaltered in the saline controls. The quality of anaesthesia was excellent in the fentanyl treated groups; however, caution is urged with the use of even low doses of fentanyl in spontaneously breathing dogs under halothane-nitrous oxide anaesthesia.     

Neuromuscular and cardiovascular effects of atracurium administered to healthy horses anesthetized with halothane

Neuromuscular and cardiovascular effects of atracurium, a nondepolarizing neuromuscular blocking agent, were evaluated in 10 halothane-anesthetized adult horses. Hind limb digital extensor tension (hoof twitch) was measured with a strain gauge to quantitate the muscle relaxant effects of atracurium. Response of facial muscles was compared with hoof twitch. Five injections of atracurium were given. Initial mean (+/- SEM) dosage of 0.07 +/- 0.01 mg of atracurium/kg of body weight caused 98.6 +/- 0.8% reduction of the preinjection hoof twitch. Subsequent dosages of 0.04 +/- 0.003 mg/kg induced a degree of relaxation similar to that induced by the initial dose. Duration of paralysis from maximal effect to 10% recovery of twitch was 12.2 +/- 1.5 minutes for the first injection. This was significantly (P less than 0.05) different from subsequent paralysis periods, which lasted approximately 7 minutes. The 10% to 75% recovery time after all injections was similar-approximately 16 minutes. The facial muscles were less affected objectively by atracurium than was the hind limb. Atracurium did not cause cardiovascular changes. When the hoof twitch had recovered to 95% of its tension before atracurium administration, 0.5 mg of edrophonium/kg, was given to antagonize neuromuscular blockade. Within 5 minutes of edrophonium administration, twitch tension exceeded that measured before atracurium administrations. Within 2 minutes of edrophonium administration, blood pressure began to increase and continued to increase approximately 10 mm of Hg above the value measured before edrophonium administration. Heart rate was not affected by edrophonium. Other muscarinic side effects of edrophonium were not observed. Of the 10 horses, 9 had good, unremarkable recovery to standing position. One horse had a violent recovery period.     

Cardiovascular effects of 7.2% hypertonic saline solution in halothane anaesthetized ponies

The haemodynamic effects of intravenously (iv) administered hypertonic saline solution (7.2%, 4 ml/kg of body weight [bwt]) were investigated in normovolaemic ponies during halothane anaesthesia (dorsal recumbent position, intermittent pressure ventilation). Heart rate, arterial blood and pulmonary artery pressures, cardiac output, and arterial blood gases were measured throughout the experiment while related haemodynamic parameters (cardiac index, systemic and pulmonary vascular resistance, stroke volume, ventricular work) were calculated.
A transient decrease in arterial blood pressure occurred during the administration of the hypertonic solution. Significant increases in cardiac output and index, stroke work, and systolic arterial pressure were observed 5 min after the administration of the hypertonic infusion. A gradual normalization of the increased parameters occurred afterwards. Heart rate and arterial blood gases remained constant throughout the study. No clinical side-effects, except for an increase in urinary production in the recovery period, were seen during and after anaesthesia.     

Effect of Ketorolac Tromethamine on Atracurium-Induced Neuromuscular Blockade in Anesthetized Dogs

Objective —The purpose of this study was to determine the effect of ketorolac tromethamine or placebo on the neuromuscular blockade induced by an infusion of atracurium in isoflurane-anesthetized dogs. Design —Randomized, controlled trial. Animals —Six healthy, adult mixed-breed dogs (five female, one male) weighing 24.8 ± 2.8 kg. Methods —Dogs were studied on two occasions with a minimum of 7 days between studies. Dogs were induced with 5% isoflurane in oxygen and maintained with 1.6 ± minimum alveolar concentration (MAC) end-tidal isoflurane. Neuromuscular blockade was assessed using the train of-four response. Once 50% depression of the first twitch (T₁) was achieved, the atracurium infusion rate was held constant for 30 minutes. Then ketorolac, 0.5 mg/kg, or the same volume of placebo (0.9% sodium chloride solution) was administered intravenously and the atracurium infusion maintained for an additional 60 minutes. Before and at 2, 5, 10, 15, 30, and 60 minutes after ketorolac or placebo, the percent depression of T₁ and the fourth twitch to the first twitch (T₄/T₁) ratio were recorded. The atracurium infusion was discontinued and the time for T₁ to recover from 50% to 75% of its original value was recorded. At 75% T₁, edrophonium, 0.5 mg/kg intravenously, was administered to antagonize the residual blockade. Results —There was no significant difference in T₁%, T₄/T₁ ratio, or recovery time after ketorolac administration compared with placebo. Conclusions —Ketorolac, 0.5 mg/kg intravenously, has no significant effect on either atracuriuminduced neuromuscular blockade or recovery time for T₁ in isoflurane-anesthetized dogs. Clinical Relevance —The concurrent use of atracurium should not be a contraindication for the administration of ketorolac for intraoperative or postoperative analgesia.     

Neuromuscular Effects of Doxacurium Chloride in Isoflurane-Anesthetized Dogs

Objective—To determine the neuromuscular effects of doxacurium chloride and to construct a dose-response curve for the drug in isoflurane-anesthetized dogs. Design—Randomized, controlled trial. Animals—Six healthy, adult, mixed-breed dogs (five female, one male) weighing 24.8 ° 2.8 kg. Methods—Anesthesia was induced with isoflurane in oxygen and maintained with 1.9% to 2.3% end-tidal isoflurane concentration. Paco₂ was maintained between 35 and 45 mm Hg with mechanical ventilation. Mechanomyography was used to quantitate the evoked twitch response of the paw after supramaximal train-of-four stimulation of the superficial peroneal nerve. After baseline values were recorded, the dogs received one of three doses of doxacurium (2.0, 3.5, 4.5 μg/kg of body weight) or a saline placebo intravenously in random order. All dogs received all treatments with at least 7 days between studies. After drug administration, the degree of maximal first twitch depression compared with baseline (T,%) was recorded. Dose-response relations of doxacurium were plotted in log dose-probit format and analyzed by linear regression to determine effective dose (ED₅₀ and ED₉₀) values for doxacurium. Results—The median log dose-probit response curve showed good data correlation (r= .999) with estimates of the ED₅₀ (2.1 μg/kg) and ED₉₀ (3.5 μg/kg) for doxacurium in isoflurane-anesthetized dogs. Mean ± SD values for T₁% (first twitch tension compared with baseline) at maximal depression after drug administration, onset (time from drug administration to maximal depression of T₁%), duration (time from maximal depression of T₁% to 25% recovery of T₁%), and recovery (time from 25% to 75% recovery of T₁%) times were 92%± 4%, 40 ± 5 minutes, 108 ± 31 minutes, and 42 ± 11 minutes for dogs treated with 3.5 μg/kg of doxacurium and 94%± 7%, 41 ± 8 minutes, 111 ± 33 minutes, and 37 ± 10 minutes for dogs treated with 4.5 μg/kg of doxacurium. Conclusion and Clinical Relevance—We conclude that doxacurium is a long-acting neuromuscular blocking agent with a slow onset of action. Doxacurium can be used to provide muscle relaxation for long surgical procedures in isoflurane-anesthetized dogs. Interpatient variability, particularly of duration of drug action, may exist in the neuromuscular response to the administration of doxacurium in dogs.     

Effects of medetomidine premedication on propofol infusion anaesthesia in dogs

Observations of cardiovascular and respiratory parameters were made on six dogs anaesthetized on two separate occasions for 120 minutes with a propofol infusion, once without premedication and once following premedication with 10 μg kg-¹ of intramuscular medetomidine. During anaesthesia the heart rate and cardiac index tended to be lower following medetomidine premedication, while the mean arterial pressure was significantly greater (p<0.05). Although the differences were not statistically significant, the systemic vascular resistance, pulmonary vascular resistance and stroke volume index were also greater in dogs given medetomidine. The mean arterial oxygen and carbon dioxide tensions were similar under both regimens, but in 2 dogs supplementary oxygen had to be administered during anaesthesia to alleviate severe hypoxaemia on both occasions they were anaesthetized. Minute and tidal volumes of respiration tended to be greater in dogs not given medetomidine but medetomidine premedication appeared to have no effect on venous admixture. Dogs given medetomidine received intramuscular atipamezole at the end of the 120 min. propofol infusion; the mean time from induction of anaesthesia to walking without ataxia was 174. min in the unpremedicated dogs and 160 min. in the dogs given atipamezole. The mean blood propofol concentration at which the dogs walked without ataxia was higher in the unpremedicated animals (2.12 ± 0.077 μg. ml-¹ compared with 1.27 ± 0.518 μg. ml-¹ in the premedicated dogs). The oxygen delivery to the tissues was lower after medetomidine premedication (p = 0.03) and the oxygen consumption was generally lower after medetomidine premedication but the difference did not achieve statistical significance. No correlation could be demonstrated between blood propofol concentration and cardiac index, systemic or pulmonary vascular resistance indices, systolic, diastolic or mean arterial blood pressures.     

Total intravenous anaesthesia in the horse with propofol

The use of propofol, solubilised in a non-ionic emulsifying agent, for the induction and maintenance of anaesthesia in experimental ponies was assessed. Pilot studies revealed that premedication with xylazine (0.5 mg/kg bodyweight [bwt]) intravenously (iv) followed by propofol (2.0 mg/kg bwt) iv provided a satisfactory smooth induction. Two infusion rates (0.15 mg/kg bwt/min and 0.2 mg/kg bwt/min) were compared for maintenance of anaesthesia. An infusion rate of 0.2 mg/kg/min produced adequate anaesthesia in these ponies. Cardiovascular changes included a decrease in arterial pressure and cardiac output during maintenance. Respiratory depression was manifested by a decrease in rate and an increase in arterial carbon dioxide tension. Recovery after 1 h anaesthesia was rapid and smooth. In conclusion, induction and maintenance of anaesthesia with propofol in premedicated ponies proved a satisfactory technique.     

Effects of slow infusion of a low dosage of endotoxin on systemic haemodynamics in conscious horses

The effects of intravenous (iv) infusion of endotoxin for 60 mins at a cumulative dosage of 0.03 micrograms/kg bodyweight on systemic arterial, right atrial and pulmonary arterial pressures, heart rate, cardiac output, and derived pulmonary vascular resistance and total peripheral vascular resistance were compared to the effects of iv infusion of saline solution in four healthy horses. Heart rate was increased significantly after endotoxin infusion, although diastolic arterial pressure, systolic arterial pressure, electronically averaged arterial pressure, cardiac output, total peripheral resistance, and right atrial pressure did not change significantly. Average pulmonary arterial pressure was increased significantly by endotoxin infusion. This was accompanied by a trend toward increased diastolic pulmonary arterial pressure (P = 0.1), systolic pulmonary arterial pressure (P = 0.08) and pulmonary vascular resistance (P = 0.07). These results suggest that low dosages of endotoxin produce pulmonary hypertension without causing hypotensive, hypodynamic shock.     

Neuromuscular blocking properties of atracurium during sevoflurane or propofol anaesthesia in dogs

OBJECTIVE: To quantify the neuromuscular blockade (NMB) produced by atracurium in either sevoflurane or propofol-anaesthetized dogs. ANIMALS: Twelve healthy, female adult mixed-breed dogs weighing 13 +/- 3 kg (range 10-22 kg). MATERIALS AND METHODS: Three doses of atracurium (0.1, 0.2 and 0.3 mg kg(-1)) were tested at 1-week intervals. Anaesthesia was induced with inhaled sevoflurane or intravenous propofol and maintained with end-tidal sevoflurane concentrations of 1.95% (1.25 x MAC) or propofol 0.6 mg kg(-1) minute(-1) respectively. Acceleromyography and train-of-four stimulation of the fibular nerve were used for the assessment of NMB. The percentage depression of the first twitch (T1) and the fourth to the first twitch ratio (T4/T1), the maximum degree of neuromuscular block achieved and surgical muscle relaxation were recorded. Before and during neuro muscular blockade (at 10 minute intervals) body temperature, ECG, arterial blood pressure, inspired and expired CO2 concentrations and SpO2 were recorded. RESULTS: Atracurium produced a dose-dependent duration of NMB in both propofol and sevoflurane-anaesthetized dogs. Duration of block was longer in dogs anaesthetized with sevoflurane. All studied doses of atracurium caused twitch depression > or =95% with little or no cardiovascular changes. CONCLUSIONS: Sevoflurane produces a clinically relevant potentiation of atracurium-induced NMB in dogs compared with propofol. CLINICAL RELEVANCE: Significant differences in the potentiation of NMB drugs are encountered with commonly used anaesthetics in the dog.     

Comparative hemodynamic effects of halothane and halothane-acepromazine at equipotent doses in dogs.

The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary arterial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twenty-five minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration.     

The cardiorespiratory effects of morphine and butorphanol in horses anaesthetised under clinical conditions

Twenty-five horses admitted for minor orthopaedic or soft tissue surgery were anaesthetised with detomidine, ketamine and halothane. Heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, blood gases and occlusion pressures were measured before and for 30 mins after intravenous (iv) injection of saline, butorphanol 0.05 mg/kg bodyweight (bwt) or morphine 0.02 or 0.05 mg/kg bwt. Drug or saline treatment induced no significant changes from pre-treatment values within a group for arterial blood pressure, heart rate, respiratory rate, arterial carbon dioxide tension, arterial oxygen tension and occlusion pressure. In conclusion, both morphine and butorphanol at the stated doses cause no adverse effects on the cardiovascular and respiratory systems of anaesthetised horses.     

Prolonging dissociative anaesthesia in horses with a repeated bolus injection

The effects of prolonging romifidine/ketamine anaesthesia in horses with a second injection of ketamine alone or both romifidine/ketamine compared with only induction injection of romifidine and tiletamine/zolazepam were studied in 6 horses anaesthetised in lateral recumbency on 3 random occasions. All horses were sedated with romifidine 0.1 mg/kg bwt iv and, on 2 occasions, anaesthesia was induced by iv injection of ketamine 2.2 mg/kg bwt. To prolong the ketamine-induced anaesthesia, either ketamine (I.1 mg/kg bwt iv) or ketamine and romifidine (I.1 mg/kg bwt and 0.04 mg/kg bwt iv, respectively) were given 18–20 min after the start of the ketamine injection for induction. On the third occasion, anaesthesia was induced by iv injection of 1.4 mg/kg bwt Zoletil (0.7 mg/kg bwt tiletamhe + 0.7 mg/kg bwt zolazepam). No statistically significant differences in the measured cardiorespiratory function were found between the 3 groups. Heart rate was decreased significantly after sedation but increased during anaesthesia. Arterial blood pressure increased after sedation and remained high during anaesthesia. A significant decrease in arterial oxygen tension was observed in all groups during anaesthesia. The muscle relaxation induced by romifidine was, in most cases, not sufficient to abolish the catalepsy following a repeated injection of ketamine alone. Zoletil or a repeated injection of ketaminehornifidine resulted in smoother anaesthesia. When additional time is required to complete surgery during field anaesthesia, it is advisable to prolong romifidine/ketamine anaesthesia with an injection of both romifidine and ketamine in healthy horses. When a longer procedure is anticipated from the start Zoletil is an alternative for induction of anaesthesia. The mean time to response to noxious stimuli and mean time spent in lateral recumbency was 28 and 38 min for the anaesthesia prolonged with ketamine, 3.5 and 43 rnin for the anaesthesia prolonged with ketaminehornifidine and 33 and 45 min for the anaesthesia with Zoletil. All horses reached a standing position at the first attempt.     

The effect of differing rates and injection sites on the amount of protamine delivered before detection of hemodynamic alterations in dogs

OBJECTIVES: To determine the effect of the route and rate of protamine administration on the amount of protamine that could be delivered before a hemodynamic reaction occurred in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty adult mixed-breed dogs weighing 25.1+/-2.5 kg. METHODS: Before vascular surgery, the dogs were heparinized to reach an activated clotting time (ACT) of 300 seconds. After completion of the vascular surgery, protamine was administered intravenously until a hemodynamic reaction was recorded. The 4 groups of dogs were given protamine at 5 mg/min (slow) or 10 mg/min (fast) via the cephalic or the jugular veins. Systemic and pulmonary arterial pressures, central venous pressure (CVP), and pulmonary arterial occlusion pressure (PAOP) were recorded before and after protamine administration. The dose of protamine was recorded when a reaction occurred, which was defined as mean arterial pressure (MAP) <60 mm Hg or mean pulmonary arterial pressure (MPAP) >20 mm Hg or more than double the baseline value. RESULTS: Significant decreases in systolic arterial pressure (SAP), MAP, and diastolic arterial pressure (DAP) and significant increases in systolic (SPAP), mean (MPAP), and diastolic (DPAP) pulmonary arterial pressures were recorded after protamine administration. The cephalic slow group had significantly fewer protamine reactions than other groups (chi-square = 8.57, P = .03, df = 3). Significantly more protamine could be delivered from the cephalic vein (52.5+/-14.5 mg) compared with the jugular vein (37.6+/-16 mg) before a reaction occurred (P = .048). CONCLUSION: The rate of administration did not have an effect on the amount of protamine delivered. Adverse reactions were minimized when protamine was administered via the cephalic vein at a slow rate. CLINICAL RELEVANCE: We would recommend delivering protamine after cardiopulmonary bypass or vascular surgery through a peripheral venous route.     

Pulmonary vascular pressures of strenuously exercising Thoroughbreds after administration of varying doses of frusemide

The frusemide dose-response for attenuation of exercise-induced pulmonary capillary hypertension was studied in 7 healthy, exercise-conditioned Thoroughbred horses using previously described haemodynamic procedures. Four different doses of frusemide were tested: 250 mg regardless of bodyweight (amounting to 0.56 +/- 0.03 mg/kg bwt), 1.0 mg/kg bwt, 1.5 mg/kg bwt and 2.0 mg/kg bwt. Frusemide was administered i.v., 4 h before exercise. Haemodynamic data were obtained at rest and during treadmill exercise performed at 14.2 m/s on a 3.5% uphill grade; this workload elicited maximal heart rate of horses. Airway endoscopy was performed post exercise to detect exercise-induced pulmonary haemorrhage (EIPH). In standing horses, frusemide administration resulted in a significant (P<0.05) decrease in mean pulmonary arterial, pulmonary capillary and pulmonary artery wedge pressures, but significant differences among the various frusemide doses were not observed. In the control experiments, exercise caused significant increments in the right atrial as well as pulmonary arterial, wedge, and capillary pressures, and all horses experienced EIPH. Following frusemide administration, the exercise-induced rise in right atrial and pulmonary vascular pressures was significantly attenuated, but significant differences between the frusemide doses of 250 mg, 1.0 mg/kg, and 1.5 mg/kg were not discerned and all horses remained positive for EIPH. Although a further significant (P<0.05) attenuation of the exercise-induced rise in pulmonary capillary blood pressure occurred when frusemide dose increased from 250 mg to 2.0 mg/kg bwt, all horses still experienced EIPH. It is concluded that a linear response to increasing frusemide dosage in terms of attenuation of the pulmonary capillary hypertension does not exist in strenuously exercising Thoroughbred horses.     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol in dogs

OBJECTIVE: To compare sedative, analgesic, and cardiopulmonary effects after IV administration of medetomidine (20 microg/kg), medetomidine-hydromorphone (20 microg of medetomidine/kg and 0.1 mg of hydromorphone/kg), and medetomidine-butorphanol (20 microg of medetomidine/kg and 0.2 mg of butorphanol tartrate/kg) in dogs. ANIMALS: 6 dogs healthy mixed-breed dogs. PROCEDURE: Instruments were surgically inserted, and heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), core body temperature, and cardiac output (CO) were measured 0, 5, 10, 15, 30, 45, and 60 minutes after injection. Cardiac index (CI), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Arterial samples for blood gas analysis were collected 0, 15, and 45 minutes after injection. Intensity of analgesia, degree of sedation, and degree of muscle relaxation were evaluated at aforementioned time points and 75, 90, 120, 150, 180, and 210 minutes after injection. RESULTS: Administration of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol was associated with increases in SAP, MAP, DAP, MPAP, PCWP, CVP, SVR, PVR, core body temperature, and PaCO2 and decreases in HR, CO, CI, SV, SI, RR, pH, and PaO2. Clinically important differences were not detected among treatments. Medetomidine-hydromorphone and medetomidine-butorphanol provided a longer duration of sedation and better quality of analgesia, compared with medetomidine alone. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine-hydromorphone or medetomidine-butorphanol is associated with improved analgesia and sedation but has cardiopulmonary effects comparable to those for medetomidine alone.     

Cardiovascular effects of romifidine in dogs

OBJECTIVE: To characterize the cardiovascular effects of romifidine at doses ranging from 5 to 100 microg/kg of body weight, IV. ANIMALS: 25 clinically normal male Beagles. PROCEDURE: Romifidine was administered IV at a dose of 5, 10, 25, 50, or 100 microg/kg (n = 5/group). Heart rate, arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, body temperature, cardiac output, and PCV were measured immediately prior to and at selected times after romifidine administration. Cardiac index, stroke index, rate-pressure product, systemic and pulmonary vascular resistance indices, and left and right ventricular stroke work indices were calculated. Degree of sedation was assessed by an observer who was blinded to the dose administered. RESULTS: Romifidine induced a decrease in heart rate, pulmonary arterial pressure, rate-pressure product, cardiac index, and right ventricular stroke work index and an increase in central venous pressure, pulmonary capillary wedge pressure, and systemic vascular resistance index. In dogs given romifidine at a dose of 25, 50, or 100 microg/kg, an initial increase followed by a prolonged decrease in arterial pressure was observed. Arterial pressure immediately decreased in dogs given romifidine at a dose of 5 or 10 microg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IV administration of romifidine induces dose-dependent cardiovascular changes in dogs. However, the 2 lowest doses (5 and 10 microg/kg) induced less cardiovascular depression, and doses > or = 25 microg/kg induced similar cardiovascular changes, suggesting that there may be a ceiling on the cardiovascular effects of romifidine.     

Haemodynamic effects of ATP in dogs during hypoxia-induced pulmonary hypertension

Pulmonary hypertension may result from an increase in vascular resistance caused by persistent hypoxia. We have investigated the effects of adenosine triphosphate (ATP), administered into the pulmonary artery, on haemodynamic changes occurring in anaesthetized adult dogs subjected to acute hypoxic pulmonary vasoconstriction. Hypoxia alone (ventilation with 10% O2/90% N2) caused significant increases in mean pulmonary arterial blood pressure (PAP), central venous pressure (CVP), and cardiac index (CI) by 71, 102 and 38%, respectively. ATP (0.03-3.0 micromol/kg/min approximately 0.02-1.65 mg/kg/min), when infused under hypoxic conditions, significantly reduced both mean PAP and systemic arterial blood pressure (ABP) in a dose-dependent manner. The maximum decrease in mean PAP amounted to 20%; mean ABP, on the other hand, was decreased by up to 52% (P<0.01). Heart rate, CI, CVP and pulmonary occlusion pressure were not dose-dependently affected by ATP. Our data indicate that while pulmonary arterial administration of ATP in mature dogs during hypoxic pulmonary hypertension causes dilation in the pulmonary vascular bed, it is even more effective in dilating the systemic vasculature. This result suggests a need for further evaluation and warrants cautious use of ATP in the treatment of hypoxic pulmonary hypertension in adult dogs.     

Urethral pressure profile and hemodynamic effects of phenoxybenzamine and prazosin in non-sedated male beagle dogs

Prazosin is a readily available alpha-adrenergic antagonist that may be useful in the management of functional urethral obstruction in companion animals. This study used urethral pressure profilometry to evaluate the urethral effects of prazosin and phenoxybenzamine in healthy, non-sedated, male Beagle dogs. Heart rate, indirect systolic, diastolic and mean arterial blood pressures were measured, and saline perfusion urethral pressure profilometry was performed at 0, 10, 20, and 40 min following intravenous administration of prazosin (0.025 mg/kg), phenoxybenzamine (0.2 mg/kg), or placebo. Maximal urethral pressure, maximal urethral closure pressure, post peak nadir, and all blood pressure parameters decreased significantly at nearly all treatment intervals following administration of prazosin compared with placebo. Less consistently significant reductions were observed following phenoxybenzamine administration. Maximal decreases in urethral pressure parameters were observed 20 min following the injection of prazosin; maximal blood pressure decreases were evident by 10 min post- injection. In this non-sedated dog model, urethral pressure profilometry was a sensitive method of detecting urethral effects of alpha antagonists. Repeatable reductions in urethral pressure measurements were observed, with prazosin effecting more consistently significant changes than phenoxybenzamine. Significant decreases in systolic, diastolic, and mean arterial blood pressures were seen with prazosin, but not phenoxybenzamine or placebo. Further study of selective alpha-1 antagonists in dogs is needed to determine appropriate oral dosing protocols that will produce maximal urethral effects with minimal hemodynamic effects, and to demonstrate clinical efficacy in dogs with functional urethral obstruction.