Roles of thromboxane A2 and 5-hydroxytryptamine in endotoxin-induced digital vasoconstriction in horses

OBJECTIVE: To evaluate the roles of 5-hydroxytryptamine (5-HT), thromboxane A2 (TxA2), and platelet-activating factor (PAF) in endotoxin-induced digital hypoperfusion in horses. ANIMALS: 6 healthy adult Thoroughbreds. PROCEDURES: Horses were treated with IV administration of saline (0.9% NaCl) solution (control treatment) or the 5-HT 1B/D selective antagonist, GR55562 (0.3 mg/kg), prior to tryptamine infusion (1.6 microg/kg/min for 30 minutes) to establish an effective GR55562 dose. In a crossover study, horses were treated with IV administration of saline solution (control treatment), aspirin (4 mg/kg, 2 hours or 4 days before lipopolysaccharide [LPS] infusion), GR55562 (0.3 mg/kg), the PAF antagonist WEB2086 (3 mg/kg), or aspirin plus GR55562 prior to LPS infusion (30 ng/kg for 30 minutes). Digital blood flow was measured by use of Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures were made. Serial blood samples were collected and plasma 5-HT and TxA2 concentrations determined. RESULTS: GR55562 abolished tryptamine-induced digital hypoperfusion. Neither WEB2086 nor GR55562 affected LPS-induced alterations in digital perfusion or plasma mediator concentrations. Aspirin given 2 hours before LPS administration abolished the increase in plasma TxA2 concentration and significantly attenuated LPS-induced digital hypoperfusion. Aspirin given 4 days before LPS significantly attenuated the increase in plasma TxA2 concentration and digital hypothermia. Aspirin plus GR55562 had a greater effect on LPS-induced digital hypothermia than aspirin alone. CONCLUSIONS AND CLINICAL RELEVANCE: Thromboxane A2 and 5-HT played a role in mediating LPS-induced digital hypoperfusion in horses. Platelet-activating factor appeared unimportant in mediating LPS-induced 5-HT or TxA2 release or digital hypoperfusion.     

Effects of subanesthetic doses of ketamine on hemodynamic and immunologic variables in dogs with experimentally induced endotoxemia

OBJECTIVE: To determine the effects of ketamine hydrochloride on hemodynamic and immunologic alterations associated with experimentally induced endotoxemia in dogs. ANIMALS: 9 mixed-breed dogs. PROCEDURES: In a crossover study, dogs were randomly allocated to receive ketamine (0.5 mg/kg, IV, followed by IV infusion at a rate of 0.12 mg/kg/h for 2.5 hours) or control solution (saline [0.9% NaCl] solution, 0.25 mL, IV, followed by IV infusion at a rate of 0.5 mL/h for 2.5 hours). Onset of infusion was time 0. At 30 minutes, lipopolysaccharide (LPS; 1 microg/kg, IV) was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma tumor necrosis factor (TNF)-alpha activity, and a CBC were evaluated. RESULTS: Mean SAP was significantly reduced in dogs administered ketamine or saline solution at 2 and 2.5 hours, compared with values at time 0. However, there was no significant difference between treatments. At 1, 2, and 2.5 hours, dogs administered ketamine had a significantly lower HR than dogs administered saline solution. Although plasma TNF-alpha activity significantly increased, compared with values at time 0 for both groups, ketamine-treated dogs had significantly lower peak plasma TNF-alpha activity 1.5 hours after LPS administration. All dogs had significant leukopenia and neutropenia after LPS administration, with no differences detected between ketamine and saline solution treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a subanesthetic dose of ketamine had immunomodulating effects in dogs with experimentally induced endotoxemia (namely, blunting of plasma TNF-alpha activity). However, it had little effect on hemodynamic stability and no effect on WBC counts.     

Effects of preemptive atropine administration on incidence of medetomidine-induced bradycardia in dogs

OBJECTIVE: To determine the cardiorespiratory effects of preemptive atropine administration in dogs sedated with medetomidine. DESIGN: Randomized crossover trial. ANIMALS: 12 healthy adult dogs. PROCEDURES: Dogs underwent 6 treatments. Each treatment consisted of administration of atropine (0.04 mg/kg [0.018 mg/lb] of body weight, IM) or saline solution (0.9% NaCl, 1 ml, IM) and administration of medetomidine (10, 20, or 40 microg/kg [4.5, 9.1, or 18.2 microg/lb], IM) 10 minutes later. Treatments were administered in random order, with a minimum of 1 week between treatments. Cardiorespiratory effects before and after atropine and medetomidine administration were assessed. Duration of lateral recumbency and quality of sedation and recovery were assessed. RESULTS: Bradycardia (heart rate < 60 beats/min) was seen in all dogs when saline solution was administered followed by medetomidine, and the dose of medetomidine was not associated with severity or frequency of bradycardia or second-degree heart block. However, a medetomidine dose-dependent increase in mean and diastolic blood pressures was observed, regardless of whether dogs received saline solution or atropine. Preemptive atropine administration effectively prevented bradycardia and second-degree heart block but induced pulsus alternans and hypertension. The protective effects of atropine against bradycardia lasted 50 minutes. Blood gas values were within reference limits during all treatments and were not significantly different from baseline values. Higher doses of medetomidine resulted in a longer duration of lateral recumbency. CONCLUSIONS AND CLINICAL RELEVANCE: Preemptive administration of atropine in dogs sedated with medetomidine effectively prevents bradycardia for 50 minutes but induces hypertension and pulsus alternans.     

Comparison of heartworm extract-induced shock and endotoxin-induced shock in dogs by determination of serum tumor necrosis factor concentrations

OBJECTIVE: To compare the mechanisms of heartworm (HW) extract-induced shock and endotoxin-induced shock in dogs by determination of serum tumor necrosis factor (TNF) concentrations. ANIMALS: 11 mixed-breed dogs (7 without and 4 with HW infections). PROCEDURE: Eight dogs were treated with 2 ml of HW extract IV, and 3 dogs were given endotoxin (Escherichia coli lipopolysaccharide [LPS]) at 40 or 400 microg/kg of body weight, IV. Changes in clinical and hematologic findings and serum TNF concentrations were examined from before treatment to 120 minutes after treatment in dogs given HW extract or from before treatment to 180 minutes after treatment in dogs given LPS. Tumor necrosis factor concentration was determined by cytotoxic assay, using WEHI-164 murine sarcoma cells, and plasma endotoxin concentration was determined in 2 dogs treated with HW extract, using the endotoxin-specific chromogenic test. RESULTS: Eight dogs developed shock 3 to 16 minutes after HW extract treatment. Rectal temperature did not change during examination. Serum TNF concentration was detected at a low concentration only 60 and 120 minutes after HW extract treatment, and plasma endotoxin was not detected during examination. In dogs treated with LPS, rectal temperature increased to > 40 C in 2 of 3 dogs, and serum TNF concentration began to increase 30 minutes after LPS treatment, reaching a maximum concentration by 60 minutes. CONCLUSIONS: The cause and mechanism of HW extract-induced shock may be different from those of endotoxin-induced shock, because TNF, which was a pivotal mediator in endotoxin-induced shock, increased minimally in serum of dogs treated with HW extract.     

Total intravenous anesthesia in greyhounds: pharmacokinetics of propofol and fentanyl--a preliminary study

OBJECTIVE: To evaluate concomitant propofol and fentanyl infusions as an anesthetic regime, in Greyhounds. ANIMALS: Eight clinically normal Greyhounds (four male, four female) weighing 25.58 +/- 3.38 kg. DESIGN: Prospective experimental study. METHODS: Dogs were premedicated with acepromazine (0.05 mg/kg) by intramuscular (i.m.) injection. Forty five minutes later anesthesia was induced with a bolus of propofol (4 mg/kg) by intravenous (i.v.) injection and a propofol infusion was begun (time = 0). Five minutes after induction of anesthesia, fentanyl (2 microg/kg) and atropine (40 microg/kg) were administered i.v. and a fentanyl infusion begun. Propofol infusion (0.2 to 0.4 mg/kg/min) lasted for 90 minutes and fentanyl infusion (0.1 to 0.5 microg/kg/min) for 70 minutes. Heart rate, blood pressure, respiratory rate, end-tidal carbon dioxide, body temperature, and depth of anesthesia were recorded. The quality of anesthesia, times to return of spontaneous ventilation, extubation, head lift, and standing were also recorded. Blood samples were collected for propofol and fentanyl analysis at varying times before, during and after anesthesia. RESULTS: Mean heart rate of all dogs varied from 52 to 140 beats/min during the infusion. During the same time period, mean blood pressure ranged from 69 to 100 mm Hg. On clinical assessment, all dogs appeared to be in light surgical anesthesia. Mean times (+/- SEM), after termination of the propofol infusion, to return of spontaneous ventilation, extubation, head lift and standing for all dogs were 26 +/- 7, 30 +/- 7, 59 +/- 12, and 105 +/- 13 minutes, respectively. Five out of eight dogs either whined or paddled their forelimbs in recovery. Whole blood concentration of propofol for all eight dogs ranged from 1.21 to 6.77 microg/mL during the infusion period. Mean residence time (MRTinf) for propofol was 104.7 +/- 6.0 minutes, mean body clearance (Clb) was 53.35 +/- 0.005 mL/kg/min, and volume of distribution at steady state (Vdss) was 3.27 +/- 0.49 L/kg. Plasma concentration of fentanyl for seven dogs during the infusion varied from 1.22 to 4.54 ng/mL. Spontaneous ventilation returned when plasma fentanyl levels were >0.77 and <1.17 ng/mL. MRTinf for fentanyl was 111.3 +/- 5.7 minutes. Mean body clearance was 29.1 +/- 2.2 mL/kg/min and Vdss was 2.21 +/- 0.19 L/kg. CONCLUSION AND CLINICAL RELEVANCE: In Greyhounds which were not undergoing any surgical stimulation, total intravenous anesthesia maintained with propofol and fentanyl infusions induced satisfactory anesthesia, provided atropine was given to counteract bradycardia. Despite some unsatisfactory recoveries the technique is worth investigating further for clinical cases, in this breed and in mixed breed dogs.     

Sedative effects of intramuscular administration of a low dose of romifidine in dogs

OBJECTIVE: To evaluate sedative effects of IM administration of a low dose of romifidine in dogs. ANIMALS: 13 healthy adult Beagles. PROCEDURE: Physiologic saline solution (0.2 ml), 0.1 % romifidine (10, 20, or 40 microg/kg), or 10% xylazine (1 mg/kg) was given IM in a crossover study design. Heart rate, respiratory rate, rectal temperature, hemoglobin saturation, and scores for sedation, muscle relaxation, posture, auditory response, and positioning response were recorded before and at regular intervals for up to 240 minutes after drug administration. RESULTS: Scores for sedation, muscle relaxation, posture, auditory response, and positioning response increased in a dose-dependent manner after romifidine administration. Sedation induced by the highest dose of romifidine (40 microg/kg) was comparable to that induced by xylazine (1 mg/kg). Heart rate, respiratory rate, and rectal temperature decreased in a dose-dependent manner after romifidine administration, but hemoglobin saturation did not change. CONCLUSIONS AND CLINICAL IMPLICATIONS: Romifidine (10, 20, or 40 microg/kg, IM) is an effective sedative in dogs, but causes a decrease in heart rate, respiratory rate, and rectal temperature.     

Changes in the minimum alveolar concentration of isoflurane and some cardiopulmonary measurements during three continuous infusion rates of dexmedetomidine in dogs

OBJECTIVE: To measure the change in the minimum alveolar concentration of isoflurane associated with three constant rate infusions of dexmedetomidine. STUDY DESIGN: Prospective, randomized, and blinded experimental trial. Animals Six healthy 6-year-old Beagles weighing between 13.0 and 17.7 kg. METHODS: The dogs received each of four treatments; saline or dexmedetomidine at 0.1, 0.5 or 3 microg kg(-1) loading dose given intravenously (IV) over 6 minutes followed by infusions at 0.1, 0.5 or 3 microg kg(-1) hour(-1), respectively. There were 2 weeks between treatments. The dogs were mask-induced with and maintained on isoflurane in oxygen. Acetated Ringer's (5 mL kg(-1) hour(-1)) and saline or dexmedetomidine (each at 0.5 mL kg(-1) hour(-1)) were given IV. Pulse rate, blood pressure, samples for the measurement of blood gases, pH, lactate, packed cell volume (PCV), total protein (TP) and dexmedetomidine concentrations were obtained from an arterial catheter. Sixty minutes after induction minimum alveolar concentration (MAC) was determined by intermittently applying supramaximal electrical stimuli to the thoracic and pelvic limbs. Cardiopulmonary measurements and arterial blood samples were collected before each set of stimuli. Statistical analyses were conducted with analysis of variance or mixed models according to the experimental design. RESULTS: There was a significant decrease in the MAC of isoflurane associated with 0.5 and 3 microg kg(-1) hour(-1) but not with 0.1 mg kg(-1)hour(-1). Serum concentrations of dexmedetomidine were not measurable at the 0.1 mg kg(-1) hour(-1) and averaged 0.198 +/- 0.081 and 1.903 +/-0.621 ng mL(-1) for the 0.5 and 3 microg kg(-1) hour(-1) infusion rates, respectively. Heart rate decreased with increasing doses of dexmedetomidine while blood pressure increased. Packed cell volume increased at 3 microg kg(-1) hour(-1) but not with other doses. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine infusions decrease the intra-operative requirement for isoflurane and may be useful in managing dogs undergoing surgery, where the provision of analgesia and limitation of the stress response is desirable.     

Cardiorespiratory responses and plasma cortisol concentrations in dogs treated with medetomidine before undergoing ovariohysterectomy

OBJECTIVE: To evaluate effects of medetomidine on anesthetic dose requirements, cardiorespiratory variables, plasma cortisol concentrations, and behavioral pain scores in dogs undergoing ovariohysterectomy. DESIGN: Randomized, prospective study. ANIMALS: 12 healthy Walker-type hound dogs. PROCEDURE: Dogs received medetomidine (40 micrograms/kg [18.2 micrograms/lb] of body weight, i.m.; n = 6) or saline (0.9% NaCl) solution (1 ml, i.m.; 6) prior to anesthesia induction with thiopental; thiopental dose needed for endotracheal intubation was compared between groups. Ovariohysterectomy was performed during halothane anesthesia. Blood samples were obtained at various times before drug administration until 300 minutes after extubation. Various physiologic measurements and end-tidal halothane concentrations were recorded. RESULTS: In medetomidine-treated dogs, heart rate was significantly lower than in controls, and blood pressure did not change significantly from baseline. Plasma cortisol concentrations did not increase significantly until 60 minutes after extubation in medetomidine-treated dogs, whereas values in control dogs were increased from time of surgery until the end of the recording period. Control dogs had higher pain scores than treated dogs from extubation until the end of the recording period. CONCLUSION AND CLINICAL RELEVANCE: Administration of medetomidine reduced dose requirements for thiopental and halothane and provided postoperative analgesia up to 90 minutes after extubation. Dogs undergoing ovariohysterectomy by use of thiopental induction and halothane anesthesia benefit from analgesia induced by medetomidine administered prior to anesthesia induction. Additional analgesia is appropriate 60 minutes after extubation.     

Evaluation of sedative and cardiorespiratory effects of romifidine and romifidine-butorphanol in cats

OBJECTIVE: To determine sedative and cardiorespiratory effects of romifidine alone and romifidine in combination with butorphanol and effects of preemptive atropine administration in cats sedated with romifidine-butorphanol. DESIGN: Randomized crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were given saline (0.9% NaCl) solution followed by romifidine alone (100 microg/kg [45.4 microg/lb], i.m.), saline solution followed by a combination of romifidine (40 microg/kg [18.1 microg/lb], i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or atropine (0.04 mg/kg [0.02 mg/lb], s.c.) followed by romifidine (40 microg/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.). Treatments were administered in random order, with > or = 1 week between treatments. Physiologic variables were determined before and after drug administration. Time to recumbency, duration of recumbency, time to recover from sedation, and subjective evaluation of sedation, muscle relaxation, and analgesia were assessed. RESULTS: Bradycardia developed in all cats that received saline solution and romifidine-butorphanol or romifidine alone. Preemptive administration of atropine prevented bradycardia for 50 minutes in cats given romifidine-butorphanol. Oxyhemoglobin saturation was significantly decreased 10 minutes after romifidine-butorphanol administration in atropine-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that administration of romifidine alone or romifidine-butorphanol causes a significant decrease in heart rate and that preemptive administration of atropine in cats sedated with romifidine-butorphanol effectively prevents bradycardia for 50 minutes.     

Evaluation of a manual technique for detection of neutropenia and thrombocytopenia in dogs receiving chemotherapy

OBJECTIVE: To determine accuracy of a manual technique for detection of neutropenia and thrombocytopenia in dogs receiving chemotherapy. DESIGN: Masked prospective study. ANIMALS: 11 dogs treated with chemotherapy for neoplasia. PROCEDURE: 124 blood samples from dogs being treated with chemotherapy for various neoplasms were processed through an automated cell counter, and results were compared with those obtained by use of a rapid manual technique for estimating neutrophil and platelet concentrations to determine whether the manual technique could accurately detect dogs with neutropenia or thrombocytopenia. RESULTS: By use of automated techniques, neutropenia (< 3,000 cells/microl) was detected in 17 of 124 blood samples, and thrombocytopenia (< 100,000 platelets/microl) was detected in 3 of 124 blood samples. The manual technique correctly identified 16 of 17 (94%) blood samples with neutropenia, with a specificity of 92% (98/107). The manual technique correctly identified 3 of 3 (100%) blood samples with thrombocytopenia, with specificity of 94% (114/121). CONCLUSIONS AND CLINICAL RELEVANCE: Manual estimates of neutrophil and platelet counts are sensitive and specific; however, a full differential cell count is still preferable.     

Butorphanol Tartrate for Partial Reversal of Oxymorphone-Induced Postoperative Respiratory Depression in the Dog

A randomized, blinded, crossover study was designed to evaluate the respiratory, cardiovascular, and behavioral effects of butorphanol given postoperatively to oxymorphone-premedicated and surgically stimulated dogs. Nine healthy adult dogs were premedicated intramuscularly with atropine (0.04 mg/kg), acepromazine (0.10 mg/kg), and oxymorphone (0.2 mg/kg). Anesthesia was induced with thiamylal (12 mg/kg) and maintained with halothane in oxygen. According to the protocol of a concurrent study, all dogs had percutaneous endoscopic gastrostomy (PEG) feeding tubes placed during the first anesthetic episode and removed during the second anesthetic episode. All dogs received postoperatively either butorphanol tartrate (0.2 mg/kg) or an isovol-umetric dose of saline placebo, both given intravenously. Respiratory rate (RR), tidal volume (TV), minute ventilation (MV), end-tidal CO₂ concentration (ET_CO2). heart rate (HR), and indirect diastolic (DP), systolic (SP) and mean arterial (MAP) blood pressures were measured at times 0, 2, 5, 10, 20, 40, 80, and 120 minutes after injection. The time from injection of the test drug until extubation was recorded. RR, MV, HR, and DP were significantly ( P < .05) increased, while ET_co2 was significantly decreased, for a minimum of 30 minutes in butorphanol-treated dogs compared with saline controls. TV, SP, and MAP were transiently (≤15 minutes) increased in butorphanol-treated dogs compared with saline controls. There was no significant difference between the times to extubation in the butorphanol-treated dogs versus the saline control dogs.     

Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).     

Effects of naloxone in treating hemorrhagic shock in dogs with maintained baroreceptor responsiveness

The efficacy of treating hemorrhagic shock with naloxone in conjunction with fluids, compared with fluid therapy alone, was studied. Previously instrumented dogs were anesthetized with 0.04 mg of fentanyl/kg + 2.2 mg of droperidol/kg and pentobarbital sodium (to effect). Blood was withdrawn from each animal to achieve and maintain a mean arterial blood pressure of 40 to 50 mm of Hg for the first 2 hours of the experiment (t = 0 to 120 minutes). At t = 120 minutes, IV fluid administration was begun (all dogs) and continued for 1 hour (lactated Ringer's solution at a dosage of 70 ml/kg/hr). Hypothermia was corrected. Control dogs were given no other treatment. Dogs in the naloxone plus fluids group were given an IV bolus of naloxone (1 mg/kg) at t = 120 minutes and 1 mg of naloxone/kg/hr in the fluids from t = 120 to t = 180 minutes. Treatment (either naloxone plus fluids or fluids alone) was stopped at t = 180 minutes, and measuring of response was continued for an additional hour (posttherapeutic period). Significant differences were not seen in mean arterial pressures, left ventricular peak systolic pressures, dP/dt max, time constant T (a measure of left ventricular elasticity), and mean pulmonary arterial pressures between the dogs given naloxone and fluid therapy and those given fluid therapy alone. All dogs in both groups survived the procedure.     

Sedative, analgesic, and cardiovascular effects of levomedetomidine alone and in combination with dexmedetomidine in dogs

OBJECTIVE: To determine whether a high dose of levomedetomidine had any pharmacologic activity or would antagonize the sedative and analgesic effects of dexmedetomidine in dogs. ANIMALS: 6 healthy Beagles. PROCEDURE: Each dog received the following treatments on separate days: a low dose of levomedetomidine (10 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 25 microg/kg/h; a high dose of levomedetomidine (80 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 200 microg/kg/h; and a dose of isotonic saline (0.9% NaCl) solution, IV, as a bolus, followed by continuous infusion (control). For all 3 treatments, the infusion was continued for 120 minutes. After 60 minutes, a single dose of dexmedetomidine (10 microg/kg) was administered IV. Sedation and analgesia were scored subjectively, and heart rate, blood pressure, respiratory rate, arterial blood gas partial pressures, and rectal temperatures were monitored. RESULTS: Administration of levomedetomidine did not cause any behavioral changes. However, administration of the higher dose of levomedetomidine enhanced the bradycardia and reduced the sedative and analgesic effects associated with administration of dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of dexmedetomidine alone may have some cardiovascular benefits over administration of medetomidine, which contains both dexmedetomidine and levomedetomidine. Further studies are needed to confirm the clinical importance of the effects of levomedetomidine in dogs.     

Acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs

OBJECTIVE: To determine acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs. ANIMALS: 14 mature healthy Beagles. PROCEDURE: 12 dogs were anesthetized with morphine and alpha-chloralose. Catheters were placed in the aorta, left ventricle, and right atrium to record systemic and pulmonary pressures and determine vascular resistance and cardiac output. Electrocardiograms (leads I, aVF, and V3) were recorded to determine electrocardiographic changes. Variables were measured before and after IV injection of incremental doses of carvedilol (cumulative doses, 10, 30, 70, 150, 310, and 630 microg/kg of body weight; n = 6) or vehicle alone (6). Pharmacokinetic analysis was performed, using 2 conscious dogs given 160 microg of carvedilol/kg as a single IV injection. RESULTS: Heart rate and velocity of fiber shortening at zero load (Vmax) increased slightly but significantly from baseline values at doses of carvedilol > or = 310 microg/kg and 10 microg/kg, respectively. Carvedilol did not affect systemic and pulmonary pressures or vascular resistances. Intravenous administration of approximately 150 microg of carvedilol/kg resulted in a plasma carvedilol concentration of approximately 100 ng/ml. Mean elimination half-life was 54 minutes, half-life of distribution was 3.5 minutes, and volume of distribution was 2,038 ml/kg. CONCLUSIONS AND CLINICAL RELEVANCE: The therapeutic plasma concentration of carvedilol in humans is 100 ng/ml. At that plasma concentration in dogs, the reduction in afterload and positive inotropic effect that we observed would be beneficial for treating heart failure and minimizing the cardiotoxic effects of doxorubicin.     

Effects of preoperative administration of ketoprofen on whole blood platelet aggregation,buccal mucosal bleeding time,and hematologic indices in dogs undergoing elective ovariohysterectomy

OBJECTIVE: To determine effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs after elective ovariohysterectomy. DESIGN: Randomized, masked clinical trial. ANIMALS: 22 healthy dogs. PROCEDURE: 60 minutes before induction of anesthesia, 11 dogs were given 0.9% NaCl solution (control), and 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], IM). Thirty minutes before induction of anesthesia, glycopyrrolate (0.01mg/kg [0.005 mg/lb]), acepromazine (0.05 mg/kg [0.02 mg/lb]), and butorphanol (0.2 mg/kg 10.09 mg/lb]) were given IM to all dogs. Anesthesia was induced with thiopental (5 to 10 mg/kg [2.3 to 4.5 mg/lb], IV) and maintained with isoflurane (1 to 3%). Ovariohysterectomy was performed and butorphanol (0.1 mg/kg [0.05 mg/lb], IV) was given 15 minutes before completion of surgery. Blood samples for measurement of variables were collected at intervals before and after surgery. RESULTS: In dogs given ketoprofen, platelet aggregation was decreased 95 +/- 10% and 80 +/- 35% (mean +/- SD) immediately after surgery and 24 hours after surgery, respectively, compared with preoperative values. At both times, mean values in dogs given ketoprofen differed significantly from those in control dogs. Significant differences between groups were not observed for mucosal bleeding time or hematologic indices. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of ketoprofen inhibited platelet aggre gation but did not alter bleeding time. Ketoprofen can be given before surgery to healthy dogs undergoing elective ovariohysterectomy, provided that dogs are screened for potential bleeding problems before surgery and monitored closely after surgery.     

A pharmacokinetic study of amoxycillin in febrile beagle dogs following repeated administrations of endotoxin

The pharmacokinetics of amoxycillin was studied in nine male beagle dogs under healthy and febrile conditions. In Period 1, dogs received 20 mg/kg of an oral suspension of amoxycillin. Intravenous doses of saline, 2 and 20 microg/kg of endotoxin (LPS from Escherichia coli serotype) were administered to dogs (three per group) prior to administration of 20 mg/kg of amoxycillin in Period 2. Rectal temperature and behavioral changes were recorded and blood samples were collected over 12 h for pharmacokinetic analysis. Amoxycillin was assessed in plasma using liquid chromatography coupled with mass spectrometry. Plasma concentrations were analysed using a one-compartment model with lag-time for absorption using an iterative two-stage method. As compared with control groups, amoxycillin clearance decreased significantly with preliminary treatments of 2 microg/kg endotoxin (0.209 vs. 0.140 L/h kg, P < 0.05) and 20 microg/kg endotoxin (0.214 vs. 0.075 L/h kg, P < 0.05). As a result of this, the area under curve for the 2 and 20 microg/kg endotoxin groups increased significantly 100.4 vs. 149.4 microg h/mL (P < 0.05) and 99.2 vs. 277.7 microg h/mL (P < 0.05), respectively. Other drugs currently used for the treatment of fever and septic shock should be re-evaluated using a febrile animal model to avoid improper dose administration.     

Comparison of Intra-articular and Epidural Morphine for Analgesia Following Stifle Arthrotomy in Dogs

We prospectively studied 18 dogs that presented for exploratory stifle arthrotomy, with or without meniscectomy, and lateral extracapsular stabilization as a result of cranial cruciate ligament rupture. Dogs were premedicated with acepromazine, induced with thiopental, and maintained with halothane in oxygen. Preoperatively, dogs were assigned to one of three groups. Group 1 (n = 6) received intra-articular morphine (0.1 mg/kg diluted in 1 mL/10 kg body weight of saline) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 2 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 3 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural morphine (0.1 mg/kg of morphine diluted in 1 mL/5 kg body weight saline). The efficacy of each analgesia regimen was evaluated for 6 hours postoperatively with a pain score based on subjective and objective variables. Serum Cortisol and blood glucose concentrations were measured. Butorphanol was used to provide analgesia as needed based on a predetermined maximum pain score. Supplemental analgesics were required postoperatively every 2 to 3 hours for 6 hours in all dogs that did not initially receive analgesics (group 2). Pain scores were significantly lower in dogs administered morphine intra-articularly (group 1) and epidurally (group 3) at 30 minutes and 30, 120, and 360 minutes, respectively, compared with dogs that did not initially receive analgesics (group 2). One dog in group 1 and one dog in group 3 required supplemental analgesia with butorphanol. There was no difference between analgesia produced by intra-articular morphine compared with that of epidural morphine. Side effects after intra-articular or epidural morphine were not observed. Intra-articular administration of morphine can produce effective analgesia in dogs comparable with that produced by epidural administration of morphine.     

Effects of carprofen on renal function during medetomidine-propofol-isoflurane anesthesia in dogs

OBJECTIVE: To investigate effects of carprofen on indices of renal function and results of serum bio-chemical analyses and effects on cardiovascular variables during medetomidine-propofol-isoflurane anesthesia in dogs. ANIMALS: 8 healthy male Beagles. PROCEDURES: A randomized crossover study was conducted with treatments including saline (0.9% NaCl) solution (0.08 mL/kg) and carprofen (4 mg/kg) administered IV. Saline solution or carprofen was administered 30 minutes before induction of anesthesia and immediately before administration of medetomidine (20 microg/kg, IM). Anesthesia was induced with propofol and maintained with inspired isoflurane in oxygen. Blood gas concentrations and ventilation were measured. Cardiovascular variables were continuously monitored via pulse contour cardiac output (CO) measurement. Renal function was assessed via glomerular filtration rate (GFR), renal blood flow (RBF), scintigraphy, serum biochemical analyses, urinalysis, and continuous CO measurements. Hematologic analysis was performed. RESULTS: Values did not differ significantly between the carprofen and saline solution groups. For both treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses; a transient, significant increase in urine alkaline phosphatase activity; and blood flow diversion to the kidneys. The GFR increased significantly in both groups despite decreased CO, mean arterial pressure, and absolute RBF variables during anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen administered IV before anesthesia did not cause detectable, significant adverse effects on renal function during medetomidine-propofol-isoflurane anesthesia in healthy Beagles.