Functional urethral obstruction in 3 dogs: clinical and urethral pressure profile findings

Three dogs with dysuria and urine retention caused by excessive functional urethral resistance are described. All dogs had clinical histories and urologic signs that previously would have been classified as detrusor-urethral dyssynergia. Diagnosis of functional urinary obstruction was established by exclusion of anatomic urinary obstruction and confirmed by urethral pressure profilometry. In 2 cases, multiple pressure deflections recorded in the urethral pressure profile suggested spasm of urethral musculature, whereas in a 3rd dog, abnormally high pressures were recorded along a portion of the proximal urethra. Functional urinary obstruction was associated with prostatitis in 1 dog and with a history of urethral calculi in 1 dog, and no underlying disorder could be identified in the remaining dog. All 3 dogs improved with medical treatments that included alpha adrenergic antagonists. The etiology, diagnosis, and pharmacologic management of functional urinary obstruction are discussed.     

Comparison of the effect of propofol and sevoflurane on the urethral pressure profile in healthy female dogs

OBJECTIVE: To compare the effects of propofol and sevoflurane on the urethral pressure profile in female dogs. ANIMALS: 10 healthy female dogs. PROCEDURE: Urethral pressure profilometry was performed in awake dogs, during anesthesia with sevoflurane at 1.5, 2.0, and 3.0% end-tidal concentration, and during infusion of propofol at rates of 0.4, 0.8, and 1.2 mg/kg/min. A consistent plane of anesthesia was maintained for each anesthetic protocol. Maximum urethral pressure, maximum urethral closure pressure, functional profile length, and functional area were measured. RESULTS: Mean maximum urethral closure pressure of awake dogs was not significantly different than that of dogs anesthetized with propofol at all infusion rates or with sevoflurane at 1.5 and 2.0% end-tidal concentration. Functional area in awake dogs was significantly higher than in anesthetized dogs. Functional area of dogs during anesthesia with sevoflurane at 3.0% end-tidal concentration was significantly lower than functional area for other anesthetic protocols. Individual differences in the magnitude of effects of propofol and sevoflurane on urethral pressures were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Sevoflurane is an alternative to propofol for anesthesia in female dogs undergoing urethral pressure profilometry. Use of these anesthetics at appropriate administration rates should reliably distinguish normal from abnormal maximum urethral closure pressures and functional areas. Titration of anesthetic depth is a critical component of urodynamic testing.     

Results of cystometry and urethral pressure profilometry in dogs sedated with medetomidine or xylazine

OBJECTIVE: To compare effects of medetomidine and xylazine hydrochloride on results of cystometry and micturition reflexes in healthy dogs and results of urethral pressure profilometry (UPP) in sedated and conscious dogs. ANIMALS: 20 dogs. PROCEDURES: Urodynamic testing was performed 6 times in each dog (3 times after administration of xylazine [1 mg/kg of body weight, IV] and 3 times after administration of medetomidine (30 microg/kg, IM). Before each episode of sedation, UPP was performed. Heart and respiratory rates and indirect blood pressures were recorded prior to and 5, 10, 20, and 30 minutes after injection of sedative. Cystometry measurements included threshold volume, threshold pressure, and tonus limb. The UPP measurements included maximal urethral closure pressure (MUCP), functional profile length, and, in male dogs, plateau pressure. RESULTS: Mean MUCP was decreased markedly in xylazine- and medetomidine-sedated dogs. Xylazine and medetomidine also decreased plateau pressure in male dogs. The MUCP measurements were consistent among days for conscious and xylazine-sedated dogs but were inconsistent for medetomidine-sedated female dogs. The proportion of valid cystometry measurements was greater for xylazine (39 of 60) than for medetomidine (27 of 60). Cystometry was considered invalid when bladder pressure reached 30 cm H2O without initiation of a micturition reflex. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and xylazine have similar effects on measurement of UPP and cystometry. Medetomidine was less consistent among days for UPP in female dogs and produced fewer valid cystometry tests, compared with xylazine. For urodynamic evaluations, medetomidine administered IM cannot be substituted for xylazine administered IV.     

Cardiovascular effects of doxacurium chloride in isoflurane-anaesthetised dogs

The cardiovascular effects of doxacurium were studied in 6 isoflurane-anaesthetised dogs. Each dog was anaesthetised twice, receiving doxacurium (0.008 mg/kg bwt) or placebo iv. Dogs were ventilated to normocapnia. Heart rate, cardiac index, systolic, diastolic, and mean arterial blood pressures, stroke volume, pulmonary vascular resistance, pulmonary artery wedge pressure, systemic vascular resistance, and pulmonary arterial pressure were determined. Neuromuscular blockade was assessed using the train-of-four technique. After recording baseline values, dogs randomly received either doxacurium or placebo iv, and data were recorded at 5, 10, 15, 30, 45, 60, 75, 90, 105 and 120 min. At 120 min, dogs treated with doxacurium received edrophonìum (0.5 mg/kg bwt iv) to antagonise neuromuscular blockade; dogs treated with placebos received saline iv. No statistically significant differences were detected after doxacurium compared to placebo. In both the doxacurium and placebo groups, significant increases in systolic arterial blood pressure, cardiac index, and stroke volume and a significant decrease in systemic vascular resistance occurred with time. Doxacurium depressed twitch tension 100% in all dogs (time to maximal twitch depression, 11 ± 7 min). First twitch tension was less than 10% of baseline values in all dogs at the time (120 min) of edrophonium administration. Additional edrophonium (1.0 ± 0.4 mg/kg iv) was required to obtain a fourth twitch to first twitch ratio of greater than 0.70. In conclusion, doxacurium is a long-acting neuromuscular blocking agent with no significant cardiovascular effects in isoflurane-anesthetised dogs. In dogs, doxacurium is indicated primarily for long surgical procedures requiring neuromuscular blockade and cardiovascular stability.     

Evaluation of the urodynamic and hemodynamic effects of orally administered phenylpropanolamine and ephedrine in female dogs

OBJECTIVE: To compare the urodynamic and hemodynamic effects of different dosages of phenylpropanolamine and ephedrine and determine effective dosages in increasing urethral resistance in female dogs. ANIMALS: 20 sexually intact female Beagles. PROCEDURE: Dogs were allocated into 4 groups and received phenylpropanolamine once, twice, or 3 times daily, or ephedrine twice daily, for 14 days. On days 0, 7, and 14, urethral pressure profiles were performed while dogs were anesthetized with propofol. Variables recorded included maximum urethral pressure, maximum urethral closure pressure, integrated pressure, functional profile length, anatomic profile length, plateau distance, distance before maximum urethral pressure, and maximum meatus pressure. Arterial and central venous pressures were measured before anesthetic induction and 10 and 35 minutes after induction. RESULTS: Administration of phenylpropanolamine once daily or ephedrine twice daily significantly increased maximum urethral pressure and maximum urethral closure pressure. Values for integrated pressure were significantly increased after 14 days of once-daily administration of phenylpropanolamine. Variables did not change significantly from day 7 to day 14. Diastolic and mean arterial blood pressures increased significantly during the treatment periods, and arterial pressure decreased during propofol infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of phenylpropanolamine once daily or ephedrine twice daily increased urethral resistance in clinically normal dogs and may be recommended for management of urethral sphincter mechanism incompetence. Treatment efficacy may be assessed after 1 week. Dogs with concurrent cardiovascular disease should be monitored for blood pressure while receiving alpha-adrenergic agents because of the effects on diastolic and mean arterial pressure.     

Urodynamic and haemodynamic effects of a single oral administration of ephedrine or phenylpropanolamine in continent female dogs

This study investigated the effects of a single oral administration of ephedrine (2 mg/kg) or phenylpropanolamine (PPA) (1.5 mg/kg) on the vesico-urethral and cardiovascular functions in continent female dogs. Urethral pressure profilometry (UPP), arterial blood pressures and heart rate were measured in five control dogs and after single-dose treatment with ephedrine or PPA at T(0), T(2h), T(4h), T(6h), T(12h), T(18h) and T(24h). UPPs were performed under propofol anaesthesia and other measurements were performed on awake dogs. A telemetric urodynamic investigation was performed on three additional dogs for 24 h after the administration of each drug. Urethral pressures increased over 4-6 h and urethral functional lengths increased 2-6h after administration of both drugs. During micturition, a decrease in detrusor pressure coupled with an increase in bladder volume was observed after ephedrine administration and there was also an increase in bladder volume after PPA had been given. With both drugs increased arterial blood pressures at 4-6 h were compensated by a decreased heart rate over 12 h. Urethral function was improved after both ephedrine and PPA, and bladder function also improved during micturition following ephedrine.     

Transobturator vaginal tape inside out for treatment of urethral sphincter mechanism incompetence: preliminary results in 7 female dogs

Objectives: To evaluate the clinical efficacy of the transobturator vaginal tape inside‐out (TVT‐O) in incontinent female dogs affected with urethral sphincter mechanism incompetence (USMI) and to determine its urodynamic and morphologic effects. Study Design: Case series. Animals: Incontinent spayed female dogs (n=7). Methods: TVT‐O tape was inserted in 7 incontinent female dogs diagnosed with USMI. Urethral pressure profilometry (UPP) and vaginourethrograms were performed preoperatively, and 1 and 3 months postoperatively. Clinical efficacy of the technique was evaluated and complications reported. Follow‐up information was evaluated by a telephone questionnaire. Results: All dogs were continent immediately after the procedure. Incontinence recurred 2 months after surgery in 1 dog and was treated by phenylpropanolamine administration. At mean follow‐up time of 11.3 months, 6 of 7 dogs were continent. An iatrogenic urethral tear occurred intraoperatively in 1 dog. No postoperative complications were encountered. The postoperative UPPs showed significantly increased maximal urethral closure pressure and integrated pressure. Postoperative vaginourethrograms were unremarkable. The surgical procedure did not modify the location of the urinary bladder neck in dogs with a “pelvic urinary bladder” preoperatively. Conclusions: TVT‐O was efficient in maintaining short term continence in 6 of 7 dogs affected with USMI.     

Effect of atropine on cystometry and urethral pressure profilometry in the dog

Effects of atropine on cystometry and urethral pressure profilometry were examined in 12 healthy young adult dogs by comparing recordings obtained after xylazine alone with those obtained after administration of xylazine and atropine. Significant differences (P greater than 0.05) were not found, indicating that atropine, when administered SC with xylazine, did not markedly affect cystometrographic results and urethral pressure profiles.     

Pharmacokinetics and cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys (Macaca mulatta)

OBJECTIVE: To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys. ANIMALS: 6 adult male rhesus monkeys. PROCEDURE: Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory. RESULTS: Heart rate and mean arterial pressure decreased transiently following fentanyl administration. Maximal decreases were observed 5 to 15 minutes after administration. Arterial pH, Paco2, and Pao2 ranged from 7.46 +/- 0.04 to 751 +/- 0.05 units, 29.2 +/- 3 to 34.6 +/- 4.4 mm Hg, and 412.6 +/- 105.3 to 482.9 +/- 71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of distribution steady state, mean residence time, area under the curve, elimination rate constant, and half-life were 32.5 +/- 2.48 ml/kg/min, 9.04 +/- 1.91 L/kg, 70 +/- 1.2 L/kg, 218.5 +/- 35.5 min, 0.247 +/- 0.019 mg/ml/min, 0.004 + 0.001/min, and 192.0 +/- 33.5 min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans.     

Urodynamic and morphologic changes in the lower portion of the urogenital tract after administration of estriol alone and in combination with phenylpropanolamine in sexually intact and spayed female dogs

OBJECTIVE: To compare the urodynamic and morphologic effects of the administration of estriol alone and in combination with phenylpropanolamine on the lower portion of the urogenital tract in female dogs. ANIMALS: 3 sexually intact and 3 spayed female Beagles without urinary incontinence. PROCEDURE: Dogs received estriol (2 mg, PO) once daily for 7 days followed by estriol (2 mg, PO) and phenylpropanolamine (1.5 mg/kg, PO) once daily for 7 days. Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed before treatment (day 0) and at days 7 and 14. The maximum urethral pressure (MUP) and closure pressure (MUCP), urethral functional and anatomic profile lengths, integrated pressure (IP), plateau, distance before MUP, maximum meatus pressure, threshold pressure, threshold volume, compliance, urethral length, and vaginal length and width were measured. RESULTS: Before treatment, no urodynamic differences were observed between the 2 groups; however, vaginal length and width were significantly shorter in spayed dogs. Compared with day 0 values, estriol treatment significantly increased MUP, MUCP, and IP values at day 7, but at day 14, this effect decreased despite phenylpropanolamine administration. No morphologic changes from baseline were detected after either treatment in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that estriol mainly acts on the urethral sphincter mechanism by increasing urethral resistance in sexually intact and spayed female dogs without urinary incontinence. Administration of estriol and phenylpropanolamine did not increase the urethral resistance more than estriol alone. The urodynamic effects of estriol in female dogs with urinary incontinence remain to be elucidated.     

Cardiovascular effects of xylazine recorded with telemetry in the dog

Cardiovascular effects of xylazine have not been studied with telemetry in dogs. In the present study, the effects on cardiovascular parameters after intramuscular (i.m.) administration of 2.0 mg/kg xylazine were studied via telemetry in unrestrained dogs. Telemetry transmitters were implanted subcutaneously (s.c.) with a pressure catheter in the femoral artery. Cardiovascular effects and body temperature effects were assessed after i.m. administration of xylazine. Heart rate decreased for about 10 min and was continuously depressed during 60 min. Thereafter, heart rate slowly increased but had not fully reached pre-dose values 4 h after treatment. Both systolic and diastolic blood pressure increased immediately after administration of xylazine. The systolic blood pressure showed a peak increase for about 5-10 min and then decreased below the baseline value not normalizing within 90 min. The diastolic blood pressure peaked 5-10 min after xylazine administration but did not return to baseline level until 50 min after administration. Body temperature decreased continuously for about 90 min and remained low for more than 4 h after treatment. An additional administration of xylazine to the same individuals after a recovery period of 4 weeks induced exactly the same response in systolic and diastolic blood pressure and in heart rate. By using the telemetric recording system it was possible to continuously evaluate xylazine-induced cardiovascular responses in a way that is not possible with conventional techniques.     

Pharmacological relaxation of the urethra in male cats: a study of the effects of phenoxybenzamine, diazepam, nifedipine and xylazine.

Urethral pressure profiles (UPPs) were recorded in ten adult healthy male cats before and after administration of either phenoxybenzamine, diazepam, nifedipine or xylazine. A significant decrease (p less than 0.05) in urethral pressure at the level of the prostate was observed following treatment with all drugs. Xylazine produced a significant decrease in urethral pressure 4 to 7 cm from the tip of the penis in healthy male cats. None of the drugs used decreased urethral pressure in the zones of pure striated muscle or pure smooth muscle in these cats, making current recommendations for pharmacological management of urethral spasm suspect. Further studies are necessary to evaluate clinical cases of urethral spasm and to study the effects of these drugs on the urethral pressure of cats suffering from this spasm.     

Validation and comparison of the use of diuresis cystometry and retrograde filling cystometry at various infusion rates in female Beagle dogs

OBJECTIVES: To compare retrograde filling cystometry at infusion rates of 5, 10, and 20 mL/min with diuresis cystometry for determination of an appropriate infusion rate and to confirm the reproducibility of measurements obtained by urethral pressure profilometry (UPP) and cystometry in female Beagles. ANIMALS: Adult female Beagles. PROCEDURE: Successive UPP and cystometry were performed by use of a water perfusion catheter on dogs anesthetized with propofol. Dogs randomly underwent each of the following at 1-week intervals: retrograde filling cystometry at 5, 10, and 20 mL/min, and diuresis cystometry. The maximum urethral pressure and closure pressure, functional and anatomic profile lengths, threshold pressure, threshold volume, and compliance were measured. RESULTS: For each UPP variable, significant differences were found among dogs, but no significant differences were found in intra- or interstudy measurements for individual dogs. For retrograde filling cystometry, threshold pressure was not significantly different between a 5 and 10 mL/min infusion rate. Threshold pressure was significantly higher during retrograde filling cystometry at 20 mL/min, compared with 5 and 10 mL/min, and was associated with bladder wall damages. Threshold pressure was significantly lower during diuresis cystometry, compared with retrograde filling cystometries. Threshold volume and compliance were not significantly different among retrograde filling cystometries but were significantly higher during diuresis cystometry. CONCLUSIONS AND CLINICAL RELEVANCE: Retrograde filling cystometry at 20 mL/min leads to unacceptable sudden increase in threshold bladder pressure. Retrograde filling cystometry at 10 mL/min can be recommended in a clinical setting, shortening the anesthesia time. However, diuresis cystometry approximates physiologic bladder filling most accurately.     

Changes in blood pressure following escalating doses of phenylpropanolamine and a suggested protocol for monitoring

This prospective, cross-over, blinded study evaluated the effect of various doses of phenylpropanolamine (PPA) on blood pressure in dogs. Dogs were randomized to receive a placebo or 1 of 3 dosages of immediate release PPA, q12h for 7 days [1 mg/kg body weight (BW), 2 mg/kg BW, or 4 mg/kg BW] in a cross-over design. Blood pressure was recorded every 2 h, for 12 h, on days 1 and 7. There were significant increases in systolic, diastolic, and mean blood pressure following administration of PPA at 2 mg/kg BW and 4 mg/kg BW. A significant decrease in heart rate was also noted at all PPA dosages, but not in the placebo. Administration of PPA was associated with a dose response increase in blood pressure. Dosages of up to 2 mg/kg BW should be considered safe in healthy dogs.     

Clinical response and urethral pressure profile changes after phenylpropanolamine in dogs with primary sphincter incompetence

Based on clinical response, urethral pressure profile changes, and lack of side effects, phenylpropanolamine was effective and safe in treating dogs with primary sphincter incompetence. Primary sphincter incompetence was diagnosed in 11 female and 8 male dogs with urinary incontinence. Urodynamics of the dogs were assessed, using a combined urethral pressure profile and urethral sphincter electromyography. Male and female dogs had significantly (P less than 0.05) lower maximal urethral closure pressures, when compared with clinically normally dogs (36.91 +/- 8.20 cm of H2O vs 79.72 +/- 4.61 cm of H2O for female dogs and 48.63 +/- 8.68 cm of H2O vs 99.77 +/- 11.71 cm of H2O for male dogs). After treatment with phenylpropanolamine, there was a significant increase in maximal urethral closure pressure in both sexes to within normal range (77.73 +/- 8.70 cm of H2O in females and 92.50 +/- 14.60 cm of H2O in males). Electromyographic activity was normal before and after treatment. Urinary incontinence resolved clinically in all but 1 male and 1 female dog; however, the condition in these 2 dogs improved considerably. Minimal side effects were seen clinically. Mean arterial blood pressure was not altered by treatment. Plasma estrogen and testosterone concentrations in 8 female dogs were not different from those in continent female dogs. The incontinence in these dogs was considered a sphincter incompetence rather than estrogen responsive.     

Use of fine-wire electrodes for electromyographic evaluation of the external urethral sphincter during urethral pressure profilometry in male cats

Evaluation of urethral pressure profilometry (UPP) with simultaneous fine-wire electromyography of the external urethral sphincter (EUS) was conducted in 11 healthy adult male cats sedated with xylazine and ketamine. A 3.5-F urethral catheter with a closed end and two 1-mm side-ports was infused with sterile 0.9% NaCl solution at a rate of 2 to 3 ml/min. A fine-wire electromyographic (EMG) electrode was placed percutaneously into or near the external urethral sphincter prior to the onset of the UPP. The maximal urethral pressure achieved and functional profile length were recorded from UPP. Setting both catheter withdrawal rate and paper speed at 5 mm/s enabled the measurement of actual urethral length directly from UPP. Sphincter EMG activity was rated as slight (+), moderate (+ +), or intense (+ + +). All recordings were replicated once during each trial for 8 cats and trials were replicated 5 to 7 days later in 4 cats. Before catheterization, EMG activity of the external urethral sphincter was rated slight (+), whereas intense (+ + +) activity accompanied insertion. The activity evoked by movement of the catheter subsided, but intense EMG activity of the external urethral sphincter was recorded from onset to completion of catheter withdrawal in all cats in both trials. The mean maximal urethral pressure was 93.1 +/- 13.29 cm H2O. The mean function urethral length was 8.1 +/- 0.93 cm. Maximal urethral pressure or function profile length did not differ significantly between recordings within trials or between trials. Simultaneous recording of EMG activity and UPP of the external urethral sphincter was shown to be a simple, noninvasive technique for assessing neuromuscular and anatomic urethral function.     

Doppler echocardiographic effects of medetomidine on dynamic left ventricular outflow tract obstruction in cats

OBJECTIVE: To evaluate the effects of medetomidine on dynamic left ventricular outflow tract (LVOT) obstruction in cats with left ventricular hypertrophy. DESIGN: Clinical trial. ANIMALS: 6 domestic shorthair cats with echocardiographic evidence of dynamic LVOT obstruction. PROCEDURE: Cats were restrained in lateral recumbency, and baseline M-mode and Doppler echocardiographic examinations were performed. An ECG was recorded continuously, and blood pressure was measured indirectly with Doppler instrumentation. Medetomidine (20 microg/kg 19.1 microg/lb]) was then administered i.m., and examinations were repeated 15 minutes later. RESULTS: Significant decreases in heart rate, LVOT velocity, and the LVOT pressure gradient were documented following medetomidine administration. After adjusting for the effects of heart rate by ANCOVA, there were no significant differences in any other systolic or diastolic indices of left ventricular function. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of medetomidine to cats with dynamic LVOT obstruction may result in elimination of outflow tract obstruction; medetomidine may be a suitable sedative and analgesic agent in this subpopulation of cats.     

The pharmacodynamics of thiopental, medetomidine, butorphanol and atropine in beagle dogs

This study evaluated the quality of anaesthesia and some of the haemodynamic effects induced by a combination of thiopental, medetomidine, butorphanol and atropine in healthy beagle dogs ( n  = 12). Following premedication with atropine (ATR, 0.022 mg/kg intravenously (i.v.)) and butorphanol (BUT, 0.22 mg/kg i.v.), medetomidine (MED, 22 μg/kg intramuscularly (i.m.)) was administered followed in 5 min by thiopental (THIO, 2.2 mg/kg i.v.). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) were monitored continuously with an ECG and direct arterial blood pressure monitor. Atipamezole (ATI, 110 μg/kg i.v.) was administered to half of the dogs ( n  = 6) following surgery to evaluate the speed and quality of arousal from anaesthesia. Anaesthesia was characterized by excellent muscle relaxation, analgesia and absence of purposeful movement in response to surgical castration. Arousal following antagonism of mede­tomidine was significantly faster ( P  < 0.05) than in unantagonized dogs. Recoveries were smooth but recovery times following atipamezole administration were highly variable among dogs (sternal time range 6–38 min, standing time range 9–56 min). Medetomidine caused a significant ( P  < 0.05) increase in SBP, DBP and MBP. Atropine prevented the medetomidine induced bradycardia. In conclusion, this combination provided adequate surgical anaesthesia in healthy beagle dogs. At the dosages used in this study, it seems prudent that this combination should be reserved for dogs free of myocardial disease.     

Short-term effects of ecadotril in dogs with induced congestive heart failure

OBJECTIVE: To evaluate short-term hemodynamic effects of ecadotril in a model of congestive heart failure in dogs. ANIMALS: 6 conscious adult male dogs. PROCEDURES: Instruments were placed in dogs to measure left ventricular, aortic, and atrial blood pressures. Heart failure was induced by repeated coronary embolization with latex microspheres. Four times, and in random order, dogs were given vehicle or active drug (3, 10, or 30 mg/kg of body weight) orally. Hemodynamic variables, urine flow, and urinary electrolyte excretion were measured before and 30, 90, and 150 minutes, and 10 and 21 hours after drug administration. RESULTS: Changes in urine flow, heart rate, mean arterial pressure, or peak positive and negative rate of change in ventricular pressure were not apparent. Urinary sodium excretion significantly increased in response to the low and high doses of ecadotril but not in response to the 10 mg/kg dose. Left ventricular end diastolic pressure (LVEDP) consistently decreased in dose- and time-dependent manner. Maximal group-averaged reductions in LVEDP were 5.2, 8.1, and 10 mm Hg for the low, middle, and high doses, respectively. The magnitude of the decrease in LVEDP was not related to cumulative change in urine flow. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered ecadotril reduced left ventricular filling pressures in these dogs by a mechanism that does not require a substantial diuretic effect. Ecadotril may be effective for alleviating clinical signs in dogs with left-sided heart failure and may be particularly beneficial for use in dogs that are refractory to traditional diuretic therapy.     

THE EFFECT OF A COMBINATION OF MEDETOMIDINE-BUTORPHANOL AND MEDETOMIDINE, BUTORPHANOL, ATROPINE ON GLOMERULAR FILTRATION RATE IN DOGS

The effects of intramuscularly administered medetomidine and butorphanol (MB), and medetomidine, butorphanol, atropine (MBA) on glomerular filtration rate (GFR) were determined in six dogs as measured by 99m-Tc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) nuclear scintigraphy. Direct systolic, diastolic, and mean arterial blood pressures and heart rate were measured at regular time intervals before, during, and after GFR calculations. The mean GFR measurement following MB was significantly greater (4.44 ml/min/kg) than following MBA (3.82 ml/min/kg) or saline treatment (3.41 ml/min/kg). There was no significant difference between the mean GFR measurements following MBA injection and following saline injection. Diastolic and mean arterial pressures following MBA injection were significantly higher than the values recorded after either MB or saline alone. Heart rate following MB administration was significantly lower than that recorded for dogs receiving MBA or saline alone. The results of this study indicate that the administration of medetomidine in combination with butorphanol significantly increases total GFR in healthy dogs, while the administration of the combination of medetomidine, butorphanol, and atropine does not.