Tony M. Glaus

Effect of Pimobendan or Benazepril Hydrochloride on Survival Times in Dogs with Congestive Heart Failure Caused by Naturally Occurring Myxomatous Mitral Valve Disease: The QUEST Study

BACKGROUND Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. HYPOTHESIS Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. ANIMALS Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. METHODS A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. RESULTS Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL IMPORTANCE Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hb-induced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO- and O2-binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.

Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma

BACKGROUND Measurement of high concentrations of urine catecholamines and metanephrines is useful in diagnosing pheochromocytoma in humans. Stress increases catecholamine excretion in urine. HYPOTHESIS Stress of a hospital visit increases urinary catecholamine and metanephrine excretion in dogs. ANIMALS Fourteen clinically normal dogs, 2 dogs with pheochromocytoma. METHODS Voided urine samples were collected by the owners 7 days before (t-7), during the hospital visit immediately after diagnostic procedures (t0), as well as 1 (t1) and 7 days (t7) after the hospital visit. Urine catecholamine and metanephrine concentrations were measured using high-pressure liquid chromatography and expressed as ratios to urine creatinine concentration. RESULTS In client-owned dogs epinephrine and norepinephrine ratios at t0 were significantly higher compared with ratios at t7. Metanephrine and normetanephrine ratios at t-7, t0, and t1 did not differ significantly from each other; however, at t7 they were significantly lower compared to values at t-7. In staff-owned dogs no significant differences were detected among the different collecting time points for any variable. Metanephrine and normetanephrine ratios were significantly higher in client-owned dogs compared to staff-owned dogs at t-7, t0, and t1 but not at t7. CONCLUSIONS AND CLINICAL IMPORTANCE Stress associated with a hospital visit and with the sampling procedure causes increases in urine catecholamine and metanephrine excretion. Urine collection for the diagnosis of pheochromocytoma probably should take place at home after adaptation to the sampling procedure.

The Effects of Hydrocortisone on Systemic Arterial Blood Pressure and Urinary Protein Excretion in Dogs

BACKGROUND Hypertension and proteinuria are commonly recognized in dogs with spontaneous hypercortisolism. There is, however, little information regarding the effect of exogenous glucocorticoids on blood pressure (BP) and proteinuria and whether these changes are reversible. HYPOTHESIS Hydrocortisone administration increases systemic BP and urinary protein excretion, and these effects are reversible after hydrocortisone withdrawal. ANIMALS Six control dogs and 6 dogs treated with hydrocortisone. METHODS BP, urine protein : creatinine ratio (UPC), microalbuminuria (MALB), urine albumin : creatinine ratio (UAC), and urine gel electrophoresis were evaluated before, during, and after administration of hydrocortisone (8 mg/kg PO q12h for 12 weeks) or placebo. RESULTS BP and UPC increased substantially during hydrocortisone administration from 123 mmHg (range 114-136 mmHg) and 0.17 (0.15-0.28) to a maximum of 143 mmHg (128-148 mmHg) and 0.38 (0.18-1.78), respectively, on day 28. MALB developed in 4 dogs and UAC significantly increased in all dogs during hydrocortisone administration with the maximum on day 84. Both increases in BP and proteinuria were reversible and completely resolved within 1 month after stopping hydrocortisone administration. SDS-AGE revealed the proteinuria to be primarily albuminuria with a pronounced increase during hydrocortisone treatment. Furthermore, a protein of 25-30 kDa was found in male dogs, identified by mass spectrometry to be arginine esterase, the major secretory prostatic protein. CONCLUSIONS AND CLINICAL IMPORTANCE Long-term hydrocortisone treatment results in significant but only mild increases in systemic BP and urinary protein excretion, which are both reversible within 1 month after discontinuation of hydrocortisone.

Effects of benazepril in the treatment of feline hypertrophic cardiomyopathy Results of a prospective, open-label, multicenter clinical trial.

OBJECTIVES To evaluate the efficacy of benazepril on clinical signs and echocardiographic parameters in cats with primary hypertrophic cardiomyopathy (HCM). BACKGROUND ACE-inhibitors have positive effects in man with HCM, and contribute to a reduction of myocardial hypertrophy. Addition of an ACE-inhibitor to the standard treatment of HCM in cats may have beneficial effects. METHODS A total of 32 cats which were either asymptomatic or in stabilised congestive heart failure (ISACHC* class Ib, II or IIIa) were included in a one-year, prospective, open-label, clinical trial in 5 centres in Switzerland. 28 of these cats were allocated to one of two treatment groups: 1) standard therapy (ST) alone (n=9), consisting of a long-acting formulation of diltiazem (6-9 mg/kg sid) and optional acetylsalicylic acid (50 mg twice weekly, or 2) the same ST plus benazepril (0.33 - 0.75 mg/kg sid, n=19). RESULTS Cats treated with benazepril showed a statistically significant decrease (mean +/- SEM, 0.11 +/- 0.03 mm/month, p = 0.002) in the left ventricular wall thickness (LVWD) from baseline, while no change (increase of 0.02 +/- 0.04 mm/month, p=0.66) was observed in cats on ST alone. Differences in LVWD between the two groups reached statistical significance (p=0.02). Benazepril treated cats showed more improvement in clinical signs (20-53%) than cats receiving ST alone (0-20%) but differences between the groups were not statistically significant (p>0.1). No change in septal thickness (IVSD) or left atrial to aortic root ratio (LA/Ao) was observed in either group. CONCLUSIONS Benazepril had some beneficial effects on clinical signs and cardiac remodelling in cats with HCM and was well tolerated. These results, however, need to be confirmed in additional controlled studies. * ISACHC classification is described in the previous paper (Bench-study).

Spontaneous Crenosoma vulpis infection in 10 dogs: laboratory, radiographic and endoscopic findings

Crenosoma (C.) vulpis infection was diagnosed in 10 dogs aged between 0.5 and 12 years (median 4 years) during a 4-year period. The predominant clinical sign in all dogs was coughing which lasted from 1 day to > 4 months. Hematological abnormalities included eosinophilia in 5/9 dogs, basophilia in 3/9 dogs, and mild monocytosis in 6/9 dogs. Thoracic radiographs (n = 9) were normal in 1 dog, showed a mild bronchial or interstitial pattern in 4 dogs, and moderate to marked changes (bronchial-interstitial to alveolar) in 4 dogs. Endoscopic findings (n = 9) varied from mild erythematous bronchitis (n = 3) to marked bronchitis with accumulation of large amounts of mucus (n = 2), irregular nodular mucosal surface (n = 2), accumulation of pus (n = 1), and bronchial hemorrhage (n = 1). Adult worms were observed in 2 dogs. Bronchial lavage cytology revealed inflammation with predominance of eosinophils in 7/10 dogs, eosinophils and neutrophils in 2/10 dogs, and neutrophils in 1/10 dogs. C. vulpis larvae were identified in the BAL of 5/10 dogs. Fecal examinations with the Baermann technique was the most sensitive method and positive in all 10 dogs. C. vulpis infection has to be considered in the differential diagnosis in dogs of all ages presenting with acute or chronic cough.

Microbiologic evaluation of gallbladder bile of healthy dogs and dogs with iatrogenic hypercortisolism: a pilot study.

BACKGROUND In people, hypercortisolism (HC) has been associated with acalculous cholecystitis and biliary dyskinesia, which may potentiate ascending biliary infections. In dogs, an association between HC and gallbladder disease recently has been documented, although the role of bacteria remains controversial. Furthermore, there is no information on the gallbladder bile microbial flora in healthy dogs. OBJECTIVES To investigate the microbial flora in gallbladder bile in healthy dogs, the relationship between iatrogenic hyperadrenocorticism and bactibilia and possible changes in biliary microbial flora after cortisol withdrawal in dogs. ANIMALS Six control dogs and 6 dogs treated with hydrocortisone. METHODS Gallbladder bile obtained by percutaneous ultrasound-guided cholecystocentesis was cultured aerobically and anaerobically and examined cytologically before (d0), during (d28, d56, d84), and after (d28p, d56p, d84p) administration of hydrocortisone (8 mg/kg PO q12h). RESULTS In the control group, 2/42 bile cultures yielded bacterial growth (Enterococcus sp.; Escherichia coli on d0) and 1/42 bile smears had cytological evidence of bacteria (d28). In the HC group, 2/42 bile cultures yielded bacterial growth (Enterococcus sp. on d28; Bacillus sp. on d28p) and 3/42 bile smears had cytological evidence of bacteria (d84, d84, d28p). All dogs remained healthy throughout the study period (168d). CONCLUSIONS AND CLINICAL IMPORTANCE Based on the results of conventional bacterial culture techniques, gallbladder bile of healthy dogs periodically may harbor bacteria, which do not appear to be clinically relevant. A 3-month period of iatrogenic HC was not associated with bactibilia. A higher prevalence of bactibilia may be detected with micromolecular techniques.

THORACIC COMPUTED TOMOGRAPHY, ANGIOGRAPHIC COMPUTED TOMOGRAPHY, AND PATHOLOGY FINDINGS IN SIX CATS EXPERIMENTALLY INFECTED WITH AELUROSTRONGYLUS ABSTRUSUS

Aelurostrongylus abstrusus infection is common in endemic areas and may cause severe respiratory clinical signs. Computed tomography (CT) is an important tool to diagnose pulmonary disease, because it allows detection of small lesions and discrimination of superimposed structures. The purpose of this study was to characterize by CT and angiographic CT the pulmonary lesions in six cats before, and 48 and 81 days after inoculation with 100 or 800 A. abstrusus infective larvae. Histological examination of the accessory lung lobe was performed to determine the microscopic, pathomorphologic correlate of the CT findings. The predominant CT lesion consisted of multiple nodules of varying size distributed throughout the lungs, severity depending on infectious dose. The histological correlate of the nodular lesions was multifocal dense granulomatous to mixed inflammatory cell infiltrates, including eosinophils distributed in the parenchyma and obliterating the alveoli. Marked, multifocal, dose-dependent thickening of the bronchi and adjacent interstitial changes blurred the margins of the outer serosal surface of the bronchi and vessels. Histologically, this was due to peribronchial mixed cell inflammation. During the course of infection some of the nodular and peribronchial changes were replaced by areas of ground-glass opacity. In addition to providing detailed depiction of pulmonary lesions resulting from an infectious cause and clearly defining lesions with respect to time and severity of infection, CT allowed quantitative assessment of bronchial thickness and lymph node size during the course of disease. Findings indicated that CT characteristics of this disease are consistent with pathologic findings.

Reproducible and long-lasting success of balloon dilation of nasopharyngeal stenosis in cats.

LIKE other nasopharyngeal disorders, nasopharyngeal stenosis leads to signs of upper airway obstruction, with stertorous breathing, dyspnoea and gagging, which are sometimes more pronounced during eating and sleeping. In cats, the first successful treatment was surgical resection of the stenotic tissue (Mitten 1988); however, several authors have described recurrences of the condition following the use of this technique (Coolman and others 1998, Novo and Kramek 1999, Glaus and others 2002). Alternative surgical techniques have been described, such as the application of a stent in addition to surgical resection (Novo and Kramek 1999), and using a mucosal advancement flap (Griffon and Tasker 2000). The first successful treatment of nasopharyngeal stenosis in a cat by balloon dilation was reported by Glaus and others (2002), and another successful balloon dilation in a cat was described by Boswood and others (2003). With the exception of the report by Mitten (1988), all of the treatments with successful outcomes were described in single case reports. This short communication describes a series of six cats with nasopharyngeal stenosis in which balloon dilation was performed and longterm follow-up was available. Between 1999 and 2003, nasopharyngeal stenosis was diagnosed endoscopically in six cats and balloon dilation was performed at the Clinic for Small Animal Internal Medicine, University of Zurich. A previously reported case is included in this series (Glaus and others 2002). There was one Siamese cat and five domestic shorthair cats; three were neutered males and three neutered females, and they ranged in age from five to 11 years (median 7·5 years) and bodyweight from 4·3 to 4·9 kg (median 4·5 kg).All the cats displayed loud, stertorous breathing. Two cats showed sporadic respiratory difficulties, characterised by increased respiratory effort and open-mouth breathing. The signs had lasted from six months to nine years (median three years) before diagnosis. One of the cats had been treated previously for upper airway infection, but in retrospect it is not known whether these signs were actually due to nasopharyngeal stenosis. In the other five cats no association with any previous disease was evident, and none of the six cats showed any signs of upper airway infection during the follow-up time. On endoscopic examination all the cats had severe nasopharyngeal stenosis (Figs 1, 2a). For the procedure the cats were placed under general anaesthesia and positioned in ventral recumbency. The whole procedure was monitored by endoscopic control from the retroflexed pharyngeal view using a flexible bronchoscope (Olympus). A well lubricated valvuloplasty balloon dilation catheter (inflated diameter 15 mm, balloon length 2 cm; Cook) was introduced through one nasal opening and passed in an orthograde fashion along the ventral nasal canal to the nasopharynx through the stenotic area, until the whole inflatable part was beyond the stenosis. In cases where the stenosis Short Communications

Pulmonary Artery Thrombosis in Experimental Angiostrongylus vasorum Infection Does Not Result in Pulmonary Hypertension and Echocardiographic Right Ventricular Changes

BACKGROUND Dogs experimentally inoculated with Angiostrongylus vasorum develop severe pulmonary parenchymal lesions and arterial thrombosis at the time of patency. HYPOTHESIS A. vasorum-induced thrombosis results in arterial hypoxemia, pulmonary hypertension (PH), and altered cardiac morphology and function. ANIMALS Six healthy Beagles experimentally inoculated with A. vasorum. METHODS Thoracic radiographs and arterial blood gas analyses were performed 8 and 13 weeks postinoculation (wpi) and 9 weeks posttherapy (wpt). Echocardiography was done before and 2, 5, 8, 13 wpi and 9 wpt. Invasive pulmonary artery pressure (PAP) measurements were obtained 8 wpi. Two untreated dogs were necropsied 13 wpi and 4 treated dogs 9 wpt. RESULTS All dogs had patent infections at 7 wpi and clinical respiratory signs at 8 wpi. Moderate hypoxemia (median PaO2 of 73 and 74 mmHg) present at 8 and 13 wpi had resolved by 9 wpt. Echocardiographically, no evidence of PH and no abnormalities in cardiac size and function were discernible at any time point. PAP invasively measured at 8 wpi was not different from that of control dogs. Severe radiographic pulmonary parenchymal and suspected thrombotic lesions at 13 wpi were corroborated by necropsy. Most histopathologic changes had resolved at 9 wpt, but focal inflammatory, thrombotic, and fibrotic changes still were present in all dogs. CONCLUSION In experimentally infected Beagles, pulmonary and vascular changes induced by A. vasorum are reflected by marked radiographic changes and arterial hypoxemia. These did not result in PH and echocardiographic changes in cardiac size and function.