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.     

Influence of the estrous cycle on urodynamic and morphometric measurements of the lower portion of the urogenital tract in dogs

OBJECTIVES: To compare the values of the urodynamic parameters of the lower portion of the urinary tract and vaginourethral measurements obtained during the phases of the estrous cycle in dogs and determine possible functional or anatomic modifications of the lower portion of the urinary tract associated with those phases. ANIMALS: 7 adult female Beagles. PROCEDURE: Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed in each dog during proestrus; estrus; early, mid, and late diestrus; and early and late anestrus. The maximum urethral pressure (MUP), maximum urethral closure pressure (MUCP), urethral functional and anatomic profile lengths (UFPL and UAPL, respectively), integrated pressure, threshold pressure, threshold volume, compliance, urethral length, and vaginal length and width were measured. RESULTS: For all measurements, significant interindividual variation was detected. Integrated and threshold pressures, APL, and each morphometric value significantly increased from late anestrus to proestrus. Compared with other phases, MUP, MUCP, and integrated pressure values were significantly lower in estrus and early diestrus; UAPL and UFPL values were significantly lower in late diestrus. At each cycle phase in old dogs, MUP, MUCP, threshold pressure, and vaginal length and width were significantly lower (except in proestrus for vaginal measurements) and threshold volume and compliance values were significantly higher, compared with middle-aged dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Urodynamic and morphometric measurements of the lower portion of the urogenital tract are affected by the changes in hormonal balance that occur during the estrous cycle. In sexually intact female dogs, estrous phase determination is important for the interpretation of urodynamic data.     

Vestibular, vaginal, and urethral relations in spayed dogs with and without lower urinary tract signs

The purpose of this study was to evaluate the urogenital anatomy in female spayed dogs with and without signs of lower urinary tract disease by using conventional vaginourethrography, computed tomography (CT) vaginourethrography, and uroendoscopy. Nineteen dogs with lower urinary tract disease and 12 normal dogs were evaluated prospectively. Measurements made included vaginal length, vaginal height, vaginal width, vestibule length, vestibule height, vestibule width, vestibulovaginal ratios, cingulum height, cingulum width, cingulum area, urethral length, urethral height, urethral width, angle of urethra to vestibule, and angle of vaginal to vestibule. Group comparisons were made between dogs with and without lower urinary tract disease. Comparisons between conventional vaginourethrography and CT vaginourethrography were made when the same anatomical measurement was made by the 2 imaging modalities. There was no significant difference in all of the measurements (P > .01), including vestibulovaginal ratios and cingulum areas, between dogs with and without lower urinary tract disease. There was a larger proportion of dogs with a vestibulovaginal ratio <0.33 in normal dogs (8 of 12) compared with the clinical dogs (8 of 16). A significant difference between vestibulovaginal ratios or cingulum areas between dogs with and without lower urinary tract disease could not be identified. This suggests that a vestibulovaginal ratio of <0.33 may only be an incidental finding and the term "vestibulovaginal stenosis" may need to be redefined.     

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.     

Differences in the expression of luteinizing hormone and follicle-stimulating hormone receptors in the lower urinary tract between intact and gonadectomised male and female dogs

Receptors for LH (LHR) and FSH (FSHR) are expressed in the canine lower urinary tract (LUT). As gonadectomy results in an increase in plasma LH and FSH, the objective of this study was to determine whether there are any differences in the expression of LHR and FSHR in the LUT between intact and gonadectomised dogs. Four regions of the LUT, i.e. body and neck of the bladder as well as proximal and distal urethra, were collected from 20 healthy dogs (5 intact males, 5 intact anoestrous females, 4 castrated males and 6 spayed females). The mRNA and protein expression of receptors was determined by in situ hybridization and immunohistochemistry, respectively, and assessed semi-quantitatively incorporating both the distribution and the intensity of specific staining. Expression of LHR and FSHR was present in all tissue layers (epithelium, sub-epithelial stroma and muscle) of each region with different levels of the expression. Overall mRNA and protein expression for both LHR and FSHR was significantly (P < 0.001) lower in gonadectomised dogs. Intact dogs had more (P < 0.05) LHR and FSHR mRNA and protein in all tissue layers of the four regions, except for LHR mRNA expression in the sub-epithelial stroma where no differences were observed between the two statuses. Decreases in LHR and FSHR mRNA and protein in gonadectomised dogs appeared to be more consistent in spayed bitches compared to castrated males. Lower expression of LHR and FSHR observed in gonadectomised dogs may adversely affect the normal canine LUT function.     

Functional anatomy and neural regulation of the lower urinary tract in female dogs: A review

Summary

A review of the literature of the functional anatomy and neural regulation of the lower urinary tract is presented. The two main functions of the lower urinary tract are the storage and the periodic elimination of urine. The smooth muscle of the bladder exhibits intermittent contractions as the bladder adapts its capacity to increasing volumes and it exhibits sustained contractions associated with relaxation of the external sphincter to effect micturition. During storage, tension receptors in the bladder wall initiate external sphincter contraction (somatic), internal sphincter contraction (sympathetic), detrusor inhibition, and parasympathetic ganglion inhibition (sympathetic). The storage phase can be switched to the micturition phase either voluntarily or involuntarily. Neuroanatomical and electrophysiological studies reveal that medial and lateral cell groups in the dorsolateral pons may be regarded as micturition and storage control centres, respectively.     

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.     

Functional anatomy and neural regulation of the lower urinary tract in female dogs: a review.

A review of the literature of the functional anatomy and neural regulation of the lower urinary tract is presented. The two main functions of the lower urinary tract are the storage and the periodic elimination of urine. The smooth muscle of the bladder exhibits intermittent contractions as the bladder adapts its capacity to increasing volumes and it exhibits sustained contractions associated with relaxation of the external sphincter to effect micturition. During storage, tension receptors in the bladder wall initiate external sphincter contraction (somatic), internal sphincter contraction (sympathetic), detrusor inhibition, and parasympathetic ganglion inhibition (sympathetic). The storage phase can be switched to the micturition phase either voluntarily or involuntarily. Neuroanatomical and electrophysiological studies reveal that medial and lateral cell groups in the dorsolateral pons may be regarded as micturition and storage control centres, respectively.     

Histomorphometry and μCT scan analysis of osteoporosis in spayed female dogs

Background:Both humans and small animals suffer from similar metabolic and structural diseases that impact the musculoskeletal system; however, instead of studying animal disease in its own right, animals are more often used as models for research into various human ailments, such as osteoporosis. There are few studies indicating that animals may suffer from osteoporosis, which raises the question of why small animals, which we believe to be equally susceptible, receive so little attention. With this research, we hope to draw the attention of researchers to the fact that the examination of animals for this disease is just as important as the examination of humans; human osteoporosis research receives a great deal of attention, while animals and their health are neglected.Aims:We aimed to analyze the bone volume fraction (BV/TV) and thickness of first (L1) and second (L2) lumbar vertebrae samples from five cadavers using histomorphometric analysis. In addition, we aimed to investigate one cadaver using microcomputed tomography (μCT) imaging.Methods:The L1 and L2 vertebrae from five dog carcasses were used to evaluate the BV/TV and the trabecular thicknesses. We used precise sampling criteria, and also developed a methodological approach to the study of the vertebrae. Using semi-automated methods, we performed histomorphometric analysis and μCT data analysis.Results:We used five dog cadavers in this research. During the histomorphometry study, we observed that the lowest L1 BV/TV ratio was 7.88% and the highest was 23.08%. The L2 vertebrae BV/TV ranged from 11.58% to 23.7%. The L1 and L2 lumbar trabeculae thicknesses were also measured. L1’s smallest trabecula was 17.34 microns and its largest was 31.88. The L2 vertebrae trabecula thickness was 18.76–30.75 microns. BV/TV and trabecular thickness were positively correlated (and vice versa). The two-tailed p value was less than 0.00001. This difference is statistically significant. After μCT analysis, we discovered regions in the vertebral body with low porosity; these cavities are usually filled with connective tissue. The bone tissue in these areas is more vulnerable, meaning fracture risk has increased.Conclusions:Animals should not just be considered as models for osteoporosis in humans, but also as potential patients. A single test, such as histomorphometry, may not be sufficient; more advanced technology, such as μCT, is required, since it reveals the pores that make the vertebral column more brittle and susceptible to fracture.     

Steroid hormone concentration profiles in healthy intact and neutered dogs before and after cosyntropin administration

The purpose of this study was to determine steroid hormone concentration profiles in healthy intact and neutered male and female dogs. Seventeen intact female dogs, 20 intact male dogs, 30 spayed female dogs, and 30 castrated male dogs were used in this study. Serum samples were collected before and 1h after cosyntropin administration, and serum concentrations were determined for cortisol, progesterone, 17-OH progesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, and estradiol. Intact male dogs had greater concentrations of DHEAS, androstenedione, and testosterone. Intact female dogs had greater concentrations of progesterone. There was no significant difference in estradiol concentration among the four groups. Intact male dogs had lower concentrations of cortisol post-stimulation. DHEAS and testosterone did not increase in response to ACTH in intact males, and estradiol concentrations did not increase in response to ACTH in any group. Results from this study will enhance interpretation of suspected adrenal and/or gonadal disorders of dogs. Because estradiol concentrations were similar in all groups of dogs, measuring estradiol may not be a useful diagnostic test. Cortisol concentrations for intact male dogs with hyperadrenocorticism may be lower than those of female or neutered dogs.     

Antinociceptive effects of epidural magnesium sulphate alone and in combination with morphine in dogs

ObjectiveTo compare the antinociceptive effects of magnesium sulphate (MgSO₄) when administered epidurally alone and in combination with morphine.Study designExperimental, randomized, ‘blinded’, crossover study.AnimalsSix healthy adult Beagle dogs.MethodsEvaluated treatments were MgSO₄ (2.5 mg kg⁻¹) alone (Mg), morphine (0.1 mg kg⁻¹) alone (Mo), MgSO₄ in combination with morphine (Mm), and sterile water (0.115 mL kg⁻¹; Co) that were injected in the lumbosacral epidural space using an epidural catheter. Antinociception was measured using the von Frey mechanical threshold device applied to the carpal pads, both sides of the thorax and metatarsi. Measurements were obtained at time points: before treatment (baseline) and 0.5, 1, 2, 4, 6, 12, 18 and 24 hours after the epidural injection. Sedation, behaviour score and presence of motor deficits were assessed. Data were analyzed using a linear mixed model and Bonferroni adjustments, with significance set at p < 0.05.ResultsThere were significant effects of treatment and time in all regions. Overall threshold values in grammes force [median (interquartile range)] when stimulation regions were combined were significantly higher in Mg [164 (135–200)], Mo [156 (129–195)] and Mm [158 (131–192)] compared to Co [145 (120–179)]. Thresholds were significantly higher compared to Co in Mg, Mo and Mm at the thorax and metatarsi, but only in Mg and Mo at the carpal pads. No motor deficits were observed at any time point. Thresholds (combined regions) were increased from baseline at one or more time points with all treatments, including control.Conclusion and clinical relevanceEpidural MgSO₄ produced an antinociceptive effect characterised by an increase in the mechanical thresholds of similar magnitude to that produced by epidural morphine, compared with the control group, without causing any motor deficits. No potentiation of morphine antinociception was observed. The onset and offset times of antinociception could not be clearly established. To what extent these results can be extrapolated to clinical cases requires further investigation.     

Pharmacokinetics of a florfenicol-tylosin combination after intravenous and intramuscular administration to beagle dogs

A pharmacokinetic study of a commercial florfenicol-tylosin (2:1) combination product was conducted in six beagle dogs after intravenous (IV) and intramuscular (IM) administration at doses of 10 mg/kg (florfenicol) and 5 mg/kg (tylosin). Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection. A rapid and nearly complete absorption of both drugs with a mean IM bioavailability of 103.9% (florfenicol) and 92.6% (tylosin), prolonged elimination half-life, and high tissue penetration with steady state volume of distribution of 2.63 l/kg (florfenicol) and 1.98 l/kg (tylosin) were observed. Additional studies, including pharmacodynamic and toxicological evaluation are required before recommendations can be made regarding the clinical application of the product in dogs.     

Hemodynamic effects in dogs after intramuscular administration of a combination of dexmedetomidine-butorphanol-tiletamine-zolazepam or dexmedetomidine-butorphanol-ketamine

Objective-To evaluate hemodynamic effects in dogs after IM administration of dexmedetomidine (7.5 μg/kg, butorphanol (0.15 mg/kg), and tiletamine-zolazepam (3 mg/kg [DBTZ]) or dexmedetomidine (15 μg/kg), butorphanol (0.3 mg/kg), and ketamine (3 mg/kg [DBK]). Animals-5 healthy adult mixed-breed dogs. Procedures-Each dog received DBTZ and DBK in a randomized crossover study with a 48-hour interval between treatments. Anesthesia was induced and maintained with sevoflurane in 100% oxygen while instrumentation with Swan-Ganz and arterial catheters was performed. Following instrumentation, hemodynamic measurements were recorded at 3.54% (1.5 times the minimum alveolar concentration) sevoflurane; then sevoflurane administration was discontinued, and dogs were allowed to recover. Six hours after cessation of sevoflurane administration, baseline hemodynamic measurements were recorded, each dog was given an IM injection of DBTZ or DBK, and hemodynamic measurements were obtained at predetermined intervals for 70 minutes. Results-DBTZ and DBK induced hypoventilation (Paco(2), approx 60 to 70 mm Hg), respiratory acidosis (pH, approx 7.2), hypertension (mean arterial blood pressure, approx 115 to 174 mm Hg), increases in systemic vascular resistance, and reflex bradycardia. Cardiac output, oxygen delivery, and oxygen consumption following DBTZ or DBK administration were similar to those following sevoflurane administration to achieve a surgical plane of anesthesia. Blood l-lactate concentrations remained within the reference range at all times for all protocols. Conclusions and Clinical Relevance-In healthy dogs, both DBTZ and DBK maintained oxygen delivery and oxygen consumption to tissues and blood lactate concentrations within the reference range. However, ventilation should be carefully monitored and assisted when necessary to prevent hypoventilation.     

Proliferative lesions of serous membranes in ovariectomised female and entire male dogs after stilboestrol administration

This paper reports the effects of prolonged stilbestrol administration in ovariectomized female dogs and some observations on the effects of this hormone on a group of male dogs. It was shown previously that ovarian tumors, which frequently metastasise to serous surfaces, can be produced in dogs by prolonged administration of stilbestrol. Total amounts of stilbestrol given to individual dogs in this study ranged from 180 to 570 mg, mainly over a period of 48 weeks. The ability of non-ovarian serous surfaces to proliferate in response to stilbestrol, independently of ovarian metastases, was studied in 5 females and 4 males. Papillary proliferations occurred on the uterine serosae in 3 females and on the testicular and epididymal serosae in 2 males. In no case was there papillary proliferation on serous membranes of non-genital organs. One of 2 entire females given stilbestrol had proliferations regarded as metastases of ovarian origin on non-genital serous membrane. In addition to ovarian changes, stilbestrol can cause primary proliferative lesions in the serous membranes of certain genital organs in both sexes. There is no evidence that serous membranes of non-genital organs be capable of a primary proliferative response to stilbestrol.     

Frequency of urinary tract infection in dogs with inflammatory skin disorders treated with ciclosporin alone or in combination with glucocorticoid therapy: a retrospective study

Background – Few studies have investigated the frequency of urinary tract infection (UTI) in dogs receiving long‐term ciclosporin therapy. Hypothesis/Objectives – The goal of the study was to investigate the frequency of UTI in dogs receiving ciclosporin with or without glucocorticoids. A secondary goal was to determine whether bacteriuria, pyuria and urine specific gravity were good predictors of UTI, and if ciclosporin dose, concurrent ketoconazole therapy, sex or duration of therapy affected the frequency of UTI. Animals – Eighty‐seven dogs with various inflammatory skin disorders and 59 control dogs with inflammatory skin conditions that had not received glucocorticoids or ciclosporin for 6 months were enrolled. Methods – This study was retrospective. The first urine culture from dogs receiving ciclosporin was compared with control dogs using Fisher’s exact test. A logistic mixed model was used to test for association between a positive bacterial culture and duration of treatment, dose of ciclosporin, concurrent ketoconazole therapy and sex. The sensitivities and specificities for bacteriuria, pyuria and urine specific gravity were determined. Results – Twenty‐six of 87 (30%) ciclosporin‐treated dogs had at least one positive culture. Compared with 3% positive control samples, 15% were positive in treated dogs (P = 0.027). The sensitivity and specificity were, respectively, 64.1 and 98.1% for bacteriuria, 74.4 and 70.9% for pyuria, and 56.4 and 65.3% for urine specific gravity. All other analysed parameters were not significantly different. Conclusions and clinical importance – The results suggest that routine urine cultures and assessment of bacteriuria by cystocentesis should be part of the monitoring for dogs on long‐term ciclosporin with and without glucocorticoids.     

Hematologic changes associated with the appearance of eccentrocytes after intragastric administration of garlic extract to dogs

OBJECTIVE: To determine whether dogs given garlic extract developed hemolytic anemia and to establish the hematologic characteristics induced experimentally by intragastric administration of garlic extract. ANIMALS: 8 healthy adult mixed-breed dogs. PROCEDURE: 4 dogs were given 1.25 ml of garlic extract/kg of body weight (5 g of whole garlic/kg) intragastrically once a day for 7 days. The remaining 4 control dogs received water instead of garlic extract. Complete blood counts were performed, and methemoglobin and erythrocyte-reduced glutathione concentrations, percentage of erythrocytes with Heinz bodies, and percentage of eccentrocytes were determined before and for 30 days after administration of the first dose of garlic extract. Ultrastructural analysis of eccentrocytes was performed. RESULTS: Compared with initial values, erythrocyte count, Hct, and hemoglobin concentration decreased to a minimum value on days 9 to 11 in dogs given garlic extract. Heinz body formation, an increase in erythrocyte-reduced glutathione concentration, and eccentrocytes were also detected in these dogs. However, no dog developed hemolytic anemia. CONCLUSIONS AND CLINICAL RELEVANCE: The constituents of garlic have the potential to oxidize erythrocyte membranes and hemoglobin, inducing hemolysis associated with the appearance of eccentrocytes in dogs. Thus, foods containing garlic should not be fed to dogs. Eccentrocytosis appears to be a major diagnostic feature of garlic-induced hemolysis in dogs.