Association between echocardiographic indexes and urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in dogs with myxomatous mitral valve disease.

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of tubular damage, and its elevation has been described in human and canine cardiorenal syndrome. The aim was to evaluate the association between echocardiographic indexes and urine NGAL (uNGAL) and uNGAL normalized to urine creatinine (uNGALC) in dogs with MMVD. This is a multicentric prospective cross-sectional study. A total of 77 dogs with MMVD at different ACVIM stages were included. All dogs underwent echocardiography, serum chemistry, and urinalysis. Echocardiographic data analyzed were shortening fraction (SF), left ventricular diastolic (LVIDDn) and systolic (LVIDSn) diameters normalized for body weight, left atrium to aortic root ratio (LA/Ao), maximal (LAVMax) and minimal (LAVMin) left atrial volumes, LA stroke volume (LASV), early diastolic mitral peak velocity (EVmax), EVmax to tissue Doppler E' wave (E/E'), aortic (VTIAo) and mitralic (VTIMit) velocity time integrals and their ratio (VTIMit/VTIAo), and tricuspid regurgitation velocity (TRVmax). In the univariate analysis LASV, TRVmax, LAVMax, LVIDDn, and VTIMit/VTIAo were independent predictors of increased uNGAL and uNGALC; however, only LASV [(OR: 1.96, 95% CI: 1.16 to 3.31) P = 0.01 for NGAL, and (OR: 2.79, 95% CI: 1.50 to 5.17) P < 0.001 for NGALC] and TRVmax [(OR: 1.73, 95% CI: 1.20-2.51) P = 0.002 for NGAL, and (OR: 1.50, 95% CI: 10.07-2.10) P = 0.015 for NGALC] remained statistically significant in the multivariable analysis. Based on our results, LASV and TRVmax are associated with increased uNGAL and uNGALC. These parameters might detect dogs with MMVD at higher risk of developing kidney damage.

Evaluation of urinary neutrophil gelatinase-associated lipocalin to detect renal tubular damage in dogs with stable myxomatous mitral valve disease.

BACKGROUND: Dogs with myxomatous mitral valve disease (MMVD) can experience progressive renal tubular damage and dysfunction. The prevalence of renal tubular damage is not known in dogs with stable MMVD. OBJECTIVE: To evaluate renal tubular damage in dogs with stable MMVD by evaluation of urinary neutrophil gelatinase-associated lipocalin (NGAL). ANIMALS: Ninety-eight MMVD dogs grouped according to the American College of Veterinary Internal Medicine (ACVIM) staging (group B1, n = 23; group B2, n = 27; group C + D, n = 48) and 46 healthy dogs. METHODS: Multicenter prospective observational study. Serum and urine chemistry including NGAL reported as uNGAL concentration (uNGAL) and normalized with urinary creatinine (uNGALC) were compared between MMVD dogs and healthy controls, and among different MMVD ACVIM stages. RESULTS: The MMVD dogs had significantly higher uNGAL and uNGALC (1204 pg/mL; range, 30-39 732 and 1816 pg/mg; range, 22-127 693, respectively) compared to healthy dogs (584 pg/mL; range, 56-4072 and 231 pg/mg; range, 15-2407, respectively; P = .002 and P < .0001, respectively). Both uNGAL and uNGALC increased with the increasing ACVIM stage (P = .001 and P < .001, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Renal tubular damage is present in dogs with stable MMVD, as measured by increased uNGAL. This tubular damage is subclinical, occurs in all stages of MMVD even in the absence of azotemia, and increases with the severity of MMVD. Reno-protective approaches to manage MMVD dogs should be explored to slow the progression of renal tubular damage in these patients.

Suspected Drinking Water Poisoning in a Domestic Kitten with Methemoglobinemia.

A 4-month-old male indoor cat was referred for dyspnea, mental dullness and weakness, which appeared two days earlier. The cat had been adopted at 3 months of age. Physical exam showed cyanosis, dyspnea and mild hypothermia. The "spot test" was supportive of methemoglobinemia. Co-oximetry blood gas analysis revealed severe methemoglobinemia (81.40%), severe hyperchloremia and mild hyponatremia. CBC, biochemistry and urinalysis were within normal limits, blood smear showed the presence of Heinz bodies. Treatment was instituted with oxygen therapy, methylene blue 1% solution, ascorbic acid, intravenous fluid therapy. The clinical course was favorable with rapid improvement of cyanosis and methemoglobinemia (4.2%). Acquired methemoglobinemia was hypothesized. Two weeks after discharge the cat was asymptomatic but mild methemoglobinemia (15.60%) and hyperchloremia were evident. Exposure to oxidants contained in drinking water was suspected so the owners were instructed to use bottled water only. One month later the cat was asymptomatic, and methemoglobinemia and chloremia were within normal limits. Even if a congenital form due to cytochrome b5 reductase deficiency cannot be ruled out, drinking water intoxication is the most likely cause of methemoglobinemia in this cat.

Efficacy of imidacloprid 10%/moxidectin 2.5% spot on (Advocate®, Advantage Multi®) and doxycycline for the treatment of natural Dirofilaria immitis infections in dogs.

Heartworm infection (also known as dirofilariosis due to Dirofilaria immitis) in dogs causes chronic pulmonary disease that, if left untreated, can lead to right-side congestive heart failure. Currently, the only registered drug for adulticide therapy in dogs with heartworm disease (HWD) is melarsomine dihydrochloride. The recent targeting of the bacterial endosymbiont Wolbachia, through antibiotic therapy of the infected host, has offered an interesting alternative for the treatment of HWD. Recent reports of the adulticide activity of an ivermectin/doxycycline combination protocol has lead the American Heartworm Society (AHS) to include in its guidelines that, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period might be considered. In the present study, 20 dogs with confirmed natural D. immitis infection were included following owner consent. Fourteen dogs were treated with a topical formulation containing 10% w/v imidacloprid and 2.5% w/v moxidectin (Advocate®, Advantage Multi®, Bayer), monthly for nine months, associated to doxycycline (10 mg/kg/BID) for the first 30 days. Six dogs were treated with melarsomine (Immiticide®, Merial) (2.5 mg/kg) at enrollment, followed one month later by two injections 24 h apart. The presence of circulating antigens and the number of microfilariae (mf) were evaluated at the moment of enrollment and then at 1, 2, 3, 4, 5, 6, 7, 8, 12, 18, 24 months post enrollment. Echocardiogram and radiographs were performed at month 0, 6, 12, 18, 24. Monthly moxidectin combined with 30 days of doxycycline eliminated circulating microfilariae within one month, thus breaking the transmission cycle very quickly. Furthermore, dogs treated with the combination protocol started to become negative for circulating antigens at 4 months from the beginning of treatment and all except one were antigen negative at 9 months. All dogs treated with melarsomine were antigen negative by 5 months from the beginning of the treatment. No dogs showed worsening of pulmonary patterns or criteria indicative of pulmonary hypertension 12 to 24 months after. For the criteria mf concentration, antigen concentration, radiography and echocardiography at 12, 18 and 24 months the non-inferiority for the moxidectin group could be proven for a non-inferiority margin of 15% for the rate difference. Dogs treated with moxidectin and doxycycline became negative for microfilariae and antigens sooner when compared to melarsomine in the present study and to dogs treated with doxycycline combined with ivermectin in studies previously published.

Use of contrast echocardiography for quantitative and qualitative evaluation of myocardial perfusion and pulmonary transit time in healthy dogs.

OBJECTIVE: To evaluate reproducibility of ejection fraction (EF), myocardial perfusion (MP), and pulmonary transit time (PTT) measured in a group of dogs by use of contrast echocardiography and to examine safety of this method by evaluating cardiac troponin I concentrations. ANIMALS: 6 healthy dogs. PROCEDURES: 2 bolus injections and a constant rate infusion of contrast agent were administered IV. Echocardiographic EF was determined by use of the area-length method and was calculated without and with contrast agent. The PTT and normalized PTT (PTT/mean R-R interval) were measured for each bolus. Constant rate infusion was used for global MP evaluation, and regional MP was calculated by use of a real-time method in 4 regions of interest of the left ventricle. Cardiac troponin I concentration was analyzed before and after contrast agent administration. Intraoberserver and interobserver variability was calculated. RESULTS: EF was easier to determine with the ultrasonographic contrast agent. For the first and second bolus, mean ± SD PTT was 1.8 ± 0.2 seconds and 2.1 ± 0.3 seconds and normalized PTT was 3.4 ± 0.3 seconds and 3.5 ± 0.3 seconds, respectively. A coefficient of variation < 15% was obtained for global MP but not for the regional MPs. No differences were detected between precontrast and postcontrast cardiac troponin I concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Contrast echocardiography appeared to be a repeat-able and safe technique for use in the evaluation of global MP and PTT in healthy dogs, and it improved delineation of the endocardial border in dogs.

Evaluation of plasma activity of matrix metalloproteinase-2 and -9 in dogs with myxomatous mitral valve disease.

OBJECTIVE: To investigate whether plasma activity of matrix metalloproteinase (MMP)-2 and -9 was associated with severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between MMP activity and dog characteristics, echocardiographic variables, systolic arterial blood pressure (SAP), heart rate, cardiac troponin I (cTnI) concentration, and C-reactive protein concentration. ANIMALS: 75 client-owned dogs. PROCEDURES: Severity of MMVD was assessed by use of echocardiography. Plasma activity of latent (pro-MMP) and active MMP-2 and -9 was analyzed via zymography. Plasma concentration of cTnI was analyzed with a high-sensitivity cTnI assay, and C-reactive protein concentration was analyzed with a canine-specific ELISA. RESULTS: Pro-MMP-9, active MMP-9, and pro-MMP-2 were detected, but active MMP-2 was not. No significant differences were found in MMP concentrations among the 4 MMVD severity groups. Activity of pro-MMP-9 decreased with decreases in SAP and was higher in male dogs than in female dogs. Activity of MMP-9 decreased with increases in left ventricular end-systolic dimension and with decreases in SAP and cTnI concentration. Left ventricular end-systolic dimension was the variable most strongly associated with MMP-9 activity. No associations were found between the activity of pro-MMP-2 and investigated variables. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma MMP-9 activity decreased with increases in the end-systolic left ventricular internal dimension and decreases in SAP. Hence, evaluation of MMP-9 activity has the potential to provide unique information about the myocardial remodeling process in dogs with MMVD.

Anatomic distribution and electrophysiologic properties of accessory atrioventricular pathways in dogs.

OBJECTIVE: To evaluate the anatomic distribution and electrophysiologic properties of accessory pathways (APs) in dogs. DESIGN: Case series. ANIMALS: 10 dogs with tachyarrhythmias associated with an AP. PROCEDURES: Each dog underwent electrophysiologic testing to determine the inducibility of documented and undocumented arrhythmias and to identify location, conduction properties, and antegrade and retrograde effective refractory periods of the APs. Radiofrequency catheter ablation was then performed. RESULTS: 15 APs were identified; 7 dogs each had a single AP, and 3 had multiple APs. Fourteen of the 15 APs were right-sided (6 right free wall, 4 posteroseptal, 3 midseptal, and 1 anteroseptal), and 1 was left-sided (left free wall). All APs conducted in an all-or-none fashion. Unidirectional retrograde conduction was observed in 11 APs, and bidirectional conduction was observed in 4. All documented tachyarrhythmias could be induced during electrophysiologic testing; atrial fibrillation was also inducible in 2 dogs. Mean +/- SD cycle duration of orthodromic atrioventricular reciprocating tachycardia was 215.80 +/- 44.87 milliseconds. Mean shortest R-R interval during atrial fibrillation was 247.33 +/- 83.17 milliseconds. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs, most APs are right-sided, had unidirectional retrograde conduction, and are associated with various arrhythmias, including orthodromic atrioventricular reciprocating tachycardia and atrial fibrillation without evidence of pre-excitation.

Radiofrequency catheter ablation of concealed accessory pathways in two dogs with symptomatic atrioventricular reciprocating tachycardia.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is widely used as a curative therapeutic strategy in human beings with paroxysmal supraventricular tachycardia (SVT), but rarely applied in animals. This report describes successful RFCA of atrioventricular accessory pathways (AP) in two dogs with episodic weakness caused by frequent paroxysms of supraventricular tachycardia. METHODS AND RESULTS: Invasive electrophysiological studies (EPS) identified two APs in the 1st dog (right postero-septal, right posterior), and one in the 2nd dog (right posterior). Programmed electrical stimulation demonstrated that all APs had only retrograde unidirectional conduction, and played a role to maintain inducible atrioventricular reciprocating tachycardia (AVRT). The bypass tracts were successfully eliminated with RFCA, with consequent prevention of AVRT induction during post-ablation EPS. At 8months follow-up, the dogs were asymptomatic, and no reoccurrence of tachycardia was seen. CONCLUSION: Concealed APs responsible for AVRT and accompanied symptoms may be safely eliminated using RFCA in dogs.