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An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs.

Background: Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations may be affected by the hydration status.Aim: This study aimed to evaluate the effect of dehydration on plasma NT-proANP and NT-proBNP concentrations in healthy dogs. Methods: This prospective study included five clinically healthy dogs. Furosemide was administered intravenously at 2–4 mg/kg every 1–2 h until completion of the dehydration model. The dehydration model was considered complete when weight loss was ≥5% and findings of dehydration on physical examination were observed. Plasma NT-proANP and NT-proBNP concentrations were compared at three time points: before the dehydration model was created (point 1), at the completion of the dehydration model (point 2), and when dehydration was judged to have improved (point 3). Association between plasma NT-proANP and NT-proBNP concentrations, and each clinical variable (physical examination, blood pressure, blood chemistry, blood gases, and echocardiography) was assessed using linear regression analysis. Results: Plasma NT-proANP concentration decreased significantly from point 2 to point 1 (p < 0.05), whereas plasma NT-proBNP concentration showed a decreasing trend but did not differ significantly between points 1 and 2. Plasma NT-proANP concentration correlated significantly with body weight (R2 = 0.178) and plasma NT-proBNP concentration (R2 = 0.284) (p < 0.05, respectively), and plasma NT-proBNP concentration correlated significantly with electrolytes (sodium, R2 = 0.439; potassium, R2 = 0.444; chloride, R2 = 0.419), and echocardiographic parameters (diastolic left ventricular internal diameter [LVIDd], R2 = 0.519; weight-standardised LVIDd, R2 = 0.535) (p < 0.01, respectively). Conclusion: The plasma NT-proANP concentrations decreased with dehydration. However, the plasma NT-proBNP concentration did not change with mild dehydration and reflected left ventricular morphology.

BACKGROUND: Ivabradine is used to treat tachycardia; unlike atenolol, it does not affect blood pressure or myocardial contractility. This study compared the impact of ivabradine and atenolol on heart rate (HR) and HR variability (HRV) during a 24 h period, feeding and sleeping times, via a Holter electrocardiogram in healthy cats. We hypothesised that ivabradine and atenolol would lower the HRs equally well, even at times of excitement and rest, such as during feeding and sleep; that ivabradine, unlike atenolol, would have an effect on HRV. METHODS: Five clinically healthy cats were used in the prospective blinded crossover study receiving 3 days of ivabradine (0.30 mg/kg per os twice daily) followed by atenolol (6.25 mg/cat per os twice daily, range 1.3-2.0 mg/kg) or receiving atenolol followed by ivabradine. A placebo period was initiated before the start of the crossover test, data obtained during that period were used as a baseline (BL). Evaluation parameters included HR and HRV, for the whole 24 h period and for feeding and sleeping times, comparing the effect of ivabradine and atenolol with BL. RESULTS: The HR for the whole 24 h, feeding and sleeping times, were significantly lower with ivabradine and atenolol, compared to BL (p < 0.05). The HRV for the whole 24 h and sleeping time were significantly higher after ivabradine compared with BL and after atenolol. CONCLUSIONS: In healthy cats, ivabradine and atenolol significantly reduced the HR regardless of excitement and rest; their effects were comparable. Ivabradine significantly increased HRV in comparison to BL whereas atenolol did not.

Background and Aim: Electrocardiography (ECG) is an adjunct for cardiac enlargement diagnosis. However, its efficacy in assessing left cardiac remodeling (left atrial and left ventricular enlargement) in dogs with myxomatous mitral valve disease (MMVD) remains unclear. This study aimed to evaluate the association between ECG parameters and left cardiac remodeling and to investigate whether the rate of change in ECG waveforms in the same individual reflected left cardiac remodeling in dogs with MMVD.Materials and Methods: This retrospective study included 20 healthy dogs and 140 dogs with MMVD. Data on clinical variables were obtained through physical examination, thoracic radiography, and echocardiography. The ECG parameters were the P-wave duration, PR interval, QRS complex duration, P-wave amplitude, R-wave amplitude, and mean electrical axis. Dogs with examination data that could be obtained multiple times during the study period were classified into the non-progressive and progressive groups.Results: Only the P-wave and QRS complex durations were selected as significant variables associated with imaging test parameters (p &lt; 0.05); they had a relatively higher discriminatory ability for the left cardiac remodeling than other ECG parameters. The rates of change in the PR interval and R-wave amplitude were significantly higher in the progressive group than in the non-progressive group.Conclusion: In dogs with MMVD, the P-wave and QRS complex durations were significantly correlated with the left cardiac remodeling indicators. Furthermore, an increased rate of change in the PR interval and R-wave amplitude in the same individual may indicate left cardiac remodeling.

OBJECTIVES: This study aimed to define the prevalence of upper urolithiasis in cats with chronic kidney disease (CKD) in a referral population, and to compare urinary calcium:creatinine ratio (UCa:Cr), and total and ionised calcium between cats with CKD with and without upper urolithiasis. METHODS: The medical records of cats diagnosed with CKD were reviewed for signalment, body weight, diet and prevalence of upper urolithiasis. Cats with preserved urine samples were further classified into two groups: urolithiasis group (upper urolithiasis identified by abdominal ultrasonography) and control group (CKD of unknown origin). Serum biochemical analysis, CKD stage, blood gas analysis, urine specific gravity and UCa:Cr were compared between groups using a two-sample t-test or Mann-Whitney U-test for continuous variable and a χ2 test or Fisher's exact test for categorical variables. Multivariable binary logistic regression analysis was used to identify risk factors. RESULTS: Among the 140 cats with CKD, the prevalence of upper urolithiasis was 73%. Fifty cats (5, 29 and 16 cats with CKD stages 1, 2 and 3, respectively) with urine samples met the inclusion criteria and were included in the analysis. Among cats with CKD, being purebred (odds ratio [OR] = 81.56; P = 0.03) and being fed dry food only (OR = 25.06; P = 0.001) were identified as independent upper urolithiasis risk factors; those with upper urolithiasis were more likely to be exclusively fed with urine-acidifying food (P <0.001) and have increased serum ionised calcium (iCa) (P = 0.044), fractional excretion of calcium (P = 0.45) and UCa:Cr (P = 0.005) than cats with CKD without upper urolithiasis. CONCLUSIONS AND RELEVANCE: Cats with CKD that were purebred, fed dry food and fed urine-acidifying food only often had upper urolithiasis. A higher UCa:Cr may be a result of increased serum iCa and may cause upper urolithiasis.

This study compared canine and feline fibroblast growth factor (FGF)-23 concentration measurements between automated chemiluminescence assay (CLEIA) and enzyme-linked immunosorbent assay (ELISA). Seventy serum samples each from dogs and cats were evaluated. FGF-23 measurements by CLEIA significantly correlated with those of ELISA in both dogs and cats. The Bland-Altman test showed that FGF-23 between CLEIA and ELISA had fixed and proportional biases, respectively, in both dogs and cats. Measurements by CLEIA were lower than those of ELISA, especially in higher serum FGF-23 concentrations. This study showed that FGF-23 concentrations in dogs and cats can be evaluated by automated CLEIA. However, FGF-23 cannot be directly compared between CLEIA and ELISA.

OBJECTIVES: This study investigated whether serum fibroblast growth factor (FGF)-23 concentrations are associated with serum total calcium (tCa) and blood ionised calcium (iCa) concentrations in cats with chronic kidney disease (CKD) and upper urolithiasis. METHODS: Serum samples and the medical records of cats with CKD with nephroliths, ureteroliths or both were investigated retrospectively. Cats with a serum creatinine concentration >250 μmol/l and/or a serum phosphorus concentration ⩾1.50 mmol/l were excluded. Based on cut-offs for serum tCa (2.70 mmol/l) or blood iCa (1.40 mmol/l), cats were divided into the following groups: total hypercalcaemia (H-tCa) (>2.70 mmol/l) and total normocalcaemia (N-tCa) (⩽2.70 mmol/l) groups, or ionised hypercalcaemia (H-iCa) (>1.40 mmol/l) and ionised normocalcaemia (N-iCa) (⩽1.40 mmol/l) groups, respectively. Serum FGF-23 concentrations were compared between groups and correlation analysis was performed. RESULTS: Thirty-two cats with CKD and upper urolithiasis were included. Serum FGF-23 concentrations in the H-tCa group (median 573 pg/ml [range 125-3888]; n = 12) were significantly higher compared with the N-tCa group (median 245 pg/ml [range 94-627]; n = 20) (P = 0.001). Serum FGF-23 concentrations in the H-iCa group (median 1479 pg/ml [range 509-3888]; n = 6) increased significantly compared with the N-iCa group (median 245 pg/ml [range 94-637]; n = 26) (P <0.001). Serum FGF-23 concentrations significantly correlated with serum tCa (r = 0.511, P = 0.003) and blood iCa concentrations (r = 0.425, P = 0.015) but not serum creatinine (r = 0.279, P = 0.122) or phosphorus concentrations (r = 0.208, P = 0.253).Conclusions and relevance Increased serum FGF-23 concentrations were associated with hypercalcaemia independently of creatinine and phosphate status in cats with CKD and upper urolithiasis.

Objective: The treatment of syncope depends largely on its possible etiology. Therefore, identifying the cause of syncope is very important in treatment planning. Herein, we report an etiology of syncope caused by pulmonary hypertension (PH) associated with canine filariasis, followed by syncope due to bradyarrhythmia 1 year later. Materials and Methods: An 8-year-old male English Cocker Spaniel was referred to our hospital for a second opinion regarding syncope that the dog had started experiencing approximately 2 months prior. Based on the examination findings, we diagnosed that the fainting was due to heartworm disease and associated PH. After increasing the dose of pimobendan (0.50 mg/kg, q12h), the syncope subsided. However, syncope recurred on the 215th day of the first episode. Results: The findings that differed from those during the initial examination were that car¬diac arrest was observed for approximately 5 sec during auscultation, along with sinus arrest. Therefore, to further investigate for syncope, a Holter electrocardiograph was obtained for 3 days. Consequently, sinus arrest was identified as the etiology of the recurrent syncope, and the patient was diagnosed with sick sinus syndrome, Rubenstein classification type II. Following cilostazol (10 mg/kg, q12h) administration, the syncope subsided. Conclusion: This case reports syncope in a dog, which typically occurs due to different etiologies. When a dog has PH, it may be important to think about the possibility of arrhythmias caused by a bigger right heart.

Background: A patch Holter electrocardiograph (P-Holter) is cordless, making it lightweight, unlike the conventional Holter electrocardiograph (C-Holter). A P-Holter can also take continuous measurements for up to 14 days without replacing the battery or SD card. Aim: To compare the performance of the P-Holter and the C-Holter in healthy cats. Additionally, we aimed to investigate whether multiday recordings with the P-Holter decrease sympathetic nerve activity or improve the accuracy of arrhythmia detection. Methods: Five healthy domestic short-haired cats were used for this study. Both a P-Holter and C-Holter were used on the first day, but only the P-Holter was used on days 2–6. The evaluated variables were the analyzable time of both Holter types, heart rate (HR), HR variability (HRV), and the number of arrhythmia occurrences. Results: For two out of the five cats, measurement of P-Holter was interrupted. Eventually, continuous recordings using the P-Holters were able to be collected from all individuals for 6 days. The 24 hours analyzable time from the P-Holter and C-Holter was almost identical (p = 0.94). The 24 hours mean HR did not differ across Holter types (p = 0.67). In addition, the timing of the occurrences of arrhythmias was almost identical to the P-Holter and C-Holter. Results of HRV suggested that sympathetic nerve activity was likely to decrease and vagal nerve activity was likely to increase after 4–5 days of measurement, compared to the second day of measurement (p < 0.05). When only the P-Holter was installed, the number of arrhythmia occurrences was similar on days 2–6. Conclusion: In this study, the P-Holter may be as useful as the C-Holter in cats with suspected intermittent arrhythmias, although the P-Holters were placed on cats without a clinical indication. However, cats may have individual differences in their adaptation to the device. P-Holter recordings taken for more than 4–5 days may allow the cat to acclimate to the device and reduce sympathetic nerve activity. The accuracy of arrhythmia detection across multiday P-Holter recordings requires further investigation using clinical cases.

BACKGROUND: Fibroblast growth factor (FGF)-23 is increased first in the sequence of changes associated with chronic kidney disease (CKD)-mineral and bone disorder. Thus, its measurement may serve as a predictive indicator of incident hyperphosphatemia. OBJECTIVES: To investigate whether serum FGF-23 concentration in normophosphatemic dogs with CKD is associated with the risk of the subsequent development of hyperphosphatemia and CKD progression. ANIMALS: Forty-two normophosphatemic dogs with CKD. METHODS: Blood samples and medical records were retrospectively investigated. Hyperphosphatemia was defined as a serum phosphorous concentration >5.0 mg/dL. Progression was defined as a >1.5-fold increase in serum creatinine concentration. The time periods and hazard ratios for these outcomes were assessed using Kaplan-Meier analysis, log-rank test, and univariate Cox regression analysis. The variables associated with the outcomes in the univariate analysis were included in the multivariate Cox regression model with backward selection. RESULTS: Serum FGF-23 concentration >528 pg/mL was associated with a shorter time to development of hyperphosphatemia (P < .001) and CKD progression (P < .001). In multiple Cox regression analysis, increased FGF-23 concentration remained a significant variable associated with these outcomes (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased FGF-23 concentration in normophosphatemic dogs with CKD was associated with significant risk of development of hyperphosphatemia, independent of CKD stage, and of the progression of CKD. Future research focusing on whether interventions that decrease FGF-23 secretion will slow the development of hyperphosphatemia and CKD progression is needed.

OBJECTIVES: The aim of this study was to investigate serum fibroblast growth factor (FGF)-23 concentrations in young and mature adult cats with chronic kidney disease (CKD). METHODS: The present study retrospectively investigated the serum samples and medical records of 1-8-year-old clinically healthy cats (control group, n = 7) and cats with CKD (n = 54). Cats with CKD were divided into four stages based on serum creatinine concentrations, according to the International Renal Interest Society (IRIS) CKD guidelines. Serum FGF-23 concentrations were compared between cats in the control group, IRIS stages 1, 2 and 3-4 CKD. Continuous variables were analysed using correlations and multiple linear regression. RESULTS: Serum FGF-23 concentrations were significantly higher in cats with IRIS stages 1, 2 and 3-4 CKD, compared with those in the control group (P = 0.02, P = 0.002 and P = 0.002, respectively). Additionally, serum FGF-23 concentrations in cats with IRIS stages 3-4 CKD had higher serum FGF-23 concentrations than those with IRIS stages 1 and 2 CKD (P = 0.04 and P = 0.02, respectively). In the multiple linear regression analysis, serum urea nitrogen concentration, serum phosphorus concentration and blood ionised calcium concentration were independent variables predicting serum FGF-23 concentration. CONCLUSIONS AND RELEVANCE: Serum FGF-23 concentrations in younger cats with CKD increased in early-stage CKD and were associated with mineral metabolic markers, as also occurs in geriatric cats.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.

Serum cystatin C levels (CysC) are used in human medicine to document progressive kidney failure. Although CysC are not thought to be useful for the diagnosis of kidney dysfunction in dogs, there has been no specific consideration of body weight as a confounding issue. The aim of this study was to assess that the utility of CysC for the diagnosis of decreased glomerular filtration rate (GFR) in smaller vs. larger dogs. In clinically healthy dogs, serum creatinine (Cre) and CysC correlate directly with body weight; we found that dogs weighing <20 kg had significantly lower CysC than those weighing ≥20 kg (0.27 ± 0.07 vs. 0.34 ± 0.05 mg/l, respectively, P<0.001). In dogs weighing <20 kg, CysC had superior diagnostic accuracy for the detection of mildly decreased plasma iohexol clearance (PCio) (<1.8 ml/min/kg) compared with Cre (sensitivity 100% vs. 80.9% and specificity 100% vs. 85.7%); this was not true for dogs weighing ≥20 kg. Additionally, using a cut-off PCio of <1.8 ml/min/kg, the area under receiver-operating characteristics curve (AUC) of CysC was significantly higher than that of Cre in dogs weighing <20 kg (P<0.05); this was not true for dogs weighing ≥20 kg (P=0.695). In conclusion, CysC is a useful marker for the detection of a mild decreasing GFR compared with Cre in dogs weighing <20 kg.

Renal proteinuria is associated with promoted renal dysfunction and a shorter survival period in dogs with chronic kidney disease (CKD). Renin angiotensin- aldosterone system inhibitors are primarily used to treat renal proteinuria. In this retrospective, open-label study, we aimed to evaluate the anti-proteinuric and anti-hypertensive effects of telmisartan (angiotensin II receptor blocker) in dogs with proteinuric CKD. A total of 28 dogs with proteinuric CKD were included in the study, all dogs received telmisartan 1 mg/kg q24h, PO. The urine protein-to-creatinine ratio (UPC), urine albumin-to-creatinine ratio (UAC) and systolic blood pressure (SBP) decreased significantly after telmisartan administration (P < 0.05). The median rate of change in UPC, UAC and SBP at Day 120 were - 65.1%, -75.9% and - 9.7%. Ten dogs (36.7%) achieved UPC < 1.0 at Day 120, of which six dogs had UPC < 0.5. A reduction of UPC to ≥50% was achieved in 10 dogs (36%) at Day 45 and 17 dogs (61%) at Day 120. Seventeen dogs (61%) had hypertension at baseline, of which 10 dogs (59%) had SBP < 160 mmHg at Day 120. Two-way repeated measures analysis of variance did not attribute the observed changes in SBP, UPC or UAC to feeding with a renal diet. In conclusion, telmisartan therapy provides anti-proteinuric and anti-hypertensive effects in dogs with proteinuric CKD.

The effects of different doses of orally administered sildenafil on pulmonary haemodynamics in dogs with pulmonary hypertension (PH) have not been documented in an invasive and quantitative manner. In this study, we examined the effects of oral sildenafil using a canine model of chronic embolic PH (CEPH). This CEPH model was created by repeatedly injecting microspheres through a catheter into the pulmonary artery under general anaesthesia at regular weekly intervals over several months. The CEPH dogs received 1, 2 or 4 mg/kg of sildenafil orally twice a day for seven days. Then, haemodynamic measurements including pulmonary artery pressure (PAP), systemic artery pressure (SAP), pulmonary artery wedge pressure (PAWP), right atrial pressure (RAP) and cardiac output (CO) were obtained after seven days of sildenafil administration via right heart catheterisation and oscillometric blood pressure measurements. Sildenafil was well tolerated in this study. Sildenafil administered at doses of 2 and 4 mg/kg significantly decreased systolic PAP compared with before administration. In addition, all doses of sildenafil significantly decreased the mean and diastolic PAP. Furthermore, 4 mg/kg of sildenafil significantly decreased PAP compared with 1 mg/kg. Sildenafil also significantly decreased pulmonary vascular resistance without notable changes in SAP or systemic vascular resistance. The PAWP, RAP and CO did not increase significantly at any doses. In conclusion, the oral administration of sildenafil to CEPH models decreased PAP in a dose-dependent manner.

BACKGROUND:Sildenafil improves autonomic dysfunction caused by pulmonary hypertension (PH) in humans, but its effect is unknown in dogs with PH. This prospective study aimed to evaluate the autonomic nervous system function of a canine model of chronic embolic PH (CEPH) and the autonomic nervous system function of a canine model of CEPH in which sildenafil was administered. METHODS:This study used five clinically healthy female beagle dogs. Evaluation parameters included hemodynamic parameters, heart rate (HR) and heart rate variability (HRV). Each evaluation parameter was compared before and after creating the CEPH model (before, BL; after, CEPHBL) and between the CEPHBL model and after the administration of sildenafil (1 mg/kg, BID) in the CEPH model dogs (CEPHSil). RESULTS:In the CEPHBL model, the hemodynamic parameters indicated cardiac hypofunction, and HR was significantly increased and HRV was significantly decreased compared with BL. Further, in the CEPHSil model, the hemodynamic parameters suggested improvement in cardiac function, and HRV was significantly increased. CONCLUSIONS:From the results of the CEPH model dogs, autonomic dysfunction was shown to occur in PH dogs. In addition, the administration of 1 mg/kg of sildenafil to CEPH model dogs may improve autonomic dysfunction.

INTRODUCTION/OBJECTIVES: The American College of Veterinary Internal Medicine (ACVIM) guidelines suggest that pimobendan should be initiated in dogs which meet all criteria of stage B2 myxomatous mitral valve disease (MMVD): murmur intensity ≥ 3/6, left atrial-to-aortic ratio ≥ 1.6, normalized left ventricular internal diameter in diastole ≥ 1.7, and vertebral heart size > 10.5. Recently, a new radiographic index for left atrial enlargement, vertebral left atrial size (VLAS), was proposed. The objective of the present study was to evaluate whether VLAS is useful in staging MMVD and if it can distinguish between ACVIM stages B1 and B2. ANIMALS: Ninety-seven client-owned dogs with MMVD were evaluated and classified as ACVIM stage B1, B2, or C-D. MATERIALS AND METHODS: The echocardiographs and radiographs of all the dogs were retrospectively evaluated to obtain left atrial-to-aortic ratio, normalized left ventricular internal diameter in diastole, and VLAS values. The data were analyzed to assess the correlation between these measurements and VLAS, and the optimal cutoff value of VLAS was determined. RESULTS: A VLAS cutoff value of 2.6 provided the greatest diagnostic accuracy for identification of dogs with ACVIM stage B2 MMVD (area under the curve, 0.96; sensitivity, 95%; specificity, 84%). A VLAS ≥2.5 exhibited the highest sensitivity (sensitivity, 100%; specificity, 78%), and a VLAS ≥ 3.1 exhibited the highest specificity (sensitivity, 47%; specificity, 100%). CONCLUSIONS: VLAS is a helpful index for monitoring MMVD using radiography. A VLAS cutoff value of 2.5 could be used to identify dogs that may benefit from echocardiography to determine if they have reached ACVIM stage B2.

Information regarding the pharmacokinetics of oral sildenafil in dogs with pulmonary hypertension is limited. In this study, we examined the pharmacokinetics of oral sildenafil in a canine model of chronic embolic pulmonary hypertension (CEPH). The CEPH model was developed by repeatedly injecting microspheres into the pulmonary arteries. The pharmacokinetics of oral sildenafil at 1, 2 and 4 mg/kg was evaluated using four dogs with pulmonary hypertension in the fasted state. The plasma concentrations of sildenafil were determined using high-performance liquid chromatography, and pharmacokinetic parameters were calculated using a noncompartmental analysis. Sildenafil was well tolerated in this study. Proportional increments in the maximum plasma concentration and area under the curve extrapolated to infinity at drug doses of 1, 2 and 4 mg/kg were detected using a power model analysis. No significant differences were observed among the three doses in the time to maximum plasma concentration. The mean residence time and elimination half-life were slightly but significantly higher at a dose of 4 mg/kg than at a dose of 1 mg/kg.

現在、アテノロールは肥大型心筋症に罹患した猫では心拍数(HR)を減少させる目的で用いられている。近年、イバブラジンは血圧と心筋収縮性に影響を与えず、アテノロールと同程度にHRを減少させる抗頻脈薬として注目されている。しかし、猫でのイバブラジンとアテノロールを比較した研究は極めて少ない。そこで、本研究では24時間の総HR、心拍変動および催不整脈性に注目して両者の効果を比較した。その結果、健康猫ではイバブラジンはアテノロールより有意に総HRを減少させること、交感神経活性を抑制し得ること、そして心室性不整脈を発生し得ることが明らかになった。(著者抄録)

血清Galectin-3(Gal-3)濃度は組織線維化のバイオマーカーとして近年注目されており、医学領域ではその有用性が報告されている。しかし、獣医学領域ではこのバイオマーカーの有効性に関する報告は少ないのが現状である。そこで、本研究では薬剤誘発性レニン-アンジオテンシン-アルドステロン系活性化モデルの犬において、抗アルドステロン薬の臓器保護効果を血清Gal-3濃度を指標に評価した。その結果、スピロノラクトン2mg/kg、SIDまたはBIDの投与で一時的ではあるが血清Gal-3濃度を有意に低下させた。したがって、これらの用量で投与した際のスピロノラクトンは臓器保護効果を得る上で有用である可能性がある。(著者抄録)

血清Galectin-3(Gal-3)濃度は組織線維化のバイオマーカーとして近年注目されており、医学領域ではその有用性が報告されている。しかし、獣医学領域ではこのバイオマーカーの有効性に関する報告は少ないのが現状である。そこで、本研究では薬剤誘発性レニン-アンジオテンシン-アルドステロン系活性化モデルの犬において、抗アルドステロン薬の臓器保護効果を血清Gal-3濃度を指標に評価した。その結果、エプレレノン5mg/kgまたは10mg/kg、SIDで、血清Gal-3濃度の有意な低下は認められなかった。したがって、これらの用量で投与した際のエプレレノンは臓器保護効果を得る上で有用でない可能性がある。そのため、犬でのエプレレノンの臓器保護効果を評価するためのさらなる研究が期待される。(著者抄録)

Basic information related to the association between right heart echocardiographic parameters and invasive pulmonary artery pressure (PAP) in dogs with pulmonary hypetension (PH) is scarce. The aim of this study was to examine the association between conventional right heart echocardiographic parameters and invasive PAP by right heart catheterization (RHC) before and after PH. Five female beagle dogs regarded as clinically healthy were used. Echocardiography and RHC were conducted before and after creating chronic embolic pulmonary hypertension (CEPH) models. The acceleration time to ejection time ratio in pulmonary artery flow profile (AT/ET), the ratio of the pulmonary artery and aortic diameter in diastole (PA/Ao), the right pulmonary artery distensibility index by M-mode method (RPAD M-mode), the normalized right ventricular internal diameter in diastole (RVIDdn), and the normalized tricuspid annular plane systolic excursion (TAPSEn) were correlated with the invasive systolic PAP (sPAP), mean PAP (mPAP) and diastolic PAP (dPAP). Multiple linear regression analysis identified AT/ET and RVIDdn as independent predictors of sPAP, PA/Ao and RVIDdn as independent predictors of mPAP, and PA/Ao and RPAD M-mode as independent predictors of dPAP. AT/ET and PA/Ao had high sensitivity and specificity for predicting CEPH. In conclusion, AT/ET, PA/Ao, RPAD M-mode, RVIDdn and TAPSEn were significantly correlated with invasive PAP and alterations in PA/Ao or AT/ET might enable clinicians to predict PH, even if tricuspid regurgitation is not observed.

Basic information related to the pharmacokinetics of sildenafil in dogs is scarce. This study aimed to describe the pharmacokinetic properties of oral sildenafil and determine the effect of feeding and dose proportionality. The effect of feeding on pharmacokinetics of sildenafil (1 mg/kg) was investigated using a crossover study with six dogs. In addition, the dose proportionality of sildenafil ranging 1–4 mg/kg was evaluated using five dogs in the fasted states. The plasma concentrations of sildenafil were determined using high-performance liquid chromatography, and pharmacokinetic parameters were calculated using a noncompartmental analysis. Sildenafil administrations were well tolerated in all studies. Feeding reduced the area under the curve extrapolated to infinity (AUCinf) and the maximum plasma concentration (Cmax) significantly. The elimination half-life (T1/2) did not differ between the fasted and the fed states. For dose proportionality, nonproportional increases in AUCinf and Cmax at 1–4 mg/kg doses were detected by a power model analysis.

テルミサルタン(TEL)はアンジオテンシンII受容体拮抗薬の1つである。慢性腎臓病のネコではTELの抗蛋白尿効果が報告されているが、イヌでの効果は不明である。今回、我々は、蛋白漏出性腎症(PLN)のイヌに対してTELを投与した場合の抗蛋白尿効果および有害事象を評価した。結果として、イヌでもTELの抗蛋白尿効果が証明され、蛋白尿が寛解(尿蛋白/クレアチニン比<0.5)した症例もいた。有害事象としては高カリウム血症が最も多く認められた。(著者抄録)