Takuma Aoki

Arteriovenous shunts resembling patent ductus arteriosus in dogs: 3 cases

Three dogs presented for the evaluation of cardiac murmurs were diagnosed with aberrant arteriovenous shunts. All cases demonstrated the following findings: 1) relatively soft continuous murmur loudest at the left heart base resembling patent ductus arteriosus (PDA); 2) shunt flow signals in the pulmonary artery on echocardiography; and 3) no PDA on selective angiography, but evidence of anomalous shunting vessels from thoracic aorta to pulmonary vasculature. An aberrant arteriovenous shunt should be considered when a continuous murmur of relatively small intensity is heard.

Assessment of left ventricular longitudinal function in cats with subclinical hypertrophic cardiomyopathy using tissue Doppler imaging and speckle tracking echocardiography.

Hypertrophic cardiomyopathy (HCM) in cats is characterized by concentric left ventricular (LV) hypertrophy and both diastolic and systolic dysfunction. Although impaired cardiac function detected by tissue Doppler imaging (TDI) in cats with HCM was previously reported, reference ranges of TDI in normal cats and cats with HCM have been reported as widely variable. Two-dimensional speckle tracking echocardiography (STE) was useful for assessment of cardiac function in human patients with HCM, but clinical utility was not known in cats. The aim of this study was to assess global and segmental LV myocardial function using STE in cats with HCM whose TDI variables were within the reference range. A total of 35 cats of different breeds were enrolled in this study. The HCM group (n=22) was cats diagnosed as HCM without left atrial enlargement and with normal TDI measurements. HCM cats were further divided into a segmental hypertrophy (S-HCM) group and a diffuse hypertrophy (D-HCM) group. The control group consisted of 13 clinically healthy cats. No cats in any group showed any clinical symptoms. Conventional echocardiography, TDI, and global and segmental STE indices were evaluated and compared between groups. Only the longitudinal strain rate during early diastole was significantly decreased in both HCM groups, even in all segments including those without hypertrophy in S-HCM group. This study suggests that STE parameters are the more sensitive variables compared with conventional TDI parameters to detect early myocardial diastolic dysfunction in cats with HCM.

Feasibility of radial and circumferential strain analysis using 2D speckle tracking echocardiography in cats

The purpose of the present study is to investigate the feasibility of strain analysis using speckle tracking echocardiography (STE) in cats and to evaluate STE variables in cats with hypertrophic cardiomyopathy (HCM). Sixteen clinically healthy cats and 17 cats with HCM were used. Radial and circumferential strain and strain rate variables in healthy cats were measured using STE to assess the feasibility. Comparisons of global strain and strain variables between healthy cats and cats with HCM were performed. Segmental assessments of left ventricle (LV) wall for strain and strain rate variables in cats with HCM were also performed. As a result, technically adequate images were obtained in 97.6% of the segments for STE analysis. Sedation using buprenorphine and acepromazine did not affect any global strain nor strain rate variable. In LV segments of cats with HCM, reduced segmental radial strain and strain rate variables had significantly related with segmental LV hypertrophy. It is concluded that STE analysis using short axis images of LV appeared to be clinically feasible in cats, having the possibility to be useful for detecting myocardial dysfunctions in cats with diseased heart.

Valproic acid, a histone deacetylase inhibitor, decreases proliferation of and induces specific neurogenic differentiation of canine adipose tissue-derived stem cells.

ABSTRACT Adipose tissue-derived stem cells (ADSCs) isolated from adult tissue have pluripotent differentiation and self-renewal capability. The tissue source of ADSCs can be obtained in large quantities and with low risks, thus highlighting the advantages of ADSCs in clinical applications. Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to affect ADSC differentiation in mice and rats; however, few studies have been performed on dogs. We aimed to examine the in vitro effect of VPA on canine ADSCs. Three days of pretreatment with VPA decreased the proliferation of ADSCs in a dose-dependent manner; VPA concentrations of 4 mM and above inhibited the proliferation of ADSCs. In parallel, VPA increased p16 and p21 mRNA expression, suggesting that VPA attenuated the proliferative activity of ADSCs by activating p16 and p21. Furthermore, the effects of VPA on adipogenic, osteogenic or neurogenic differentiation were investigated morphologically. VPA pretreatment markedly promoted neurogenic differentiation, but suppressed the accumulation of lipid droplets and calcium depositions. These modifications of ADSCs by VPA were associated with a particular gene expression profile, viz., an increase in neuronal markers, that is, NSE, TUBB3 and MAP2, a decrease in the adipogenic marker, LPL, but no changes in osteogenic markers, as estimated by reverse transcription-PCR analysis. These results suggested that VPA is a specific inducer of neurogenic differentiation of canine ADSCs and is a useful tool for studying the interaction between chromatin structure and cell fate determination.

Partial Anomalous Pulmonary Venous Connection in 2 Miniature Schnauzers

A 3-year-old, 6.0 kg, intact female Miniature Schnauzer was presented to Azabu University for evaluation of right heart enlargement, incidentally noticed on survey thoracic radiographs. The dog was asymptomatic and no abnormalities were identified on physical examination. Radiographic evaluation of the thorax indicated right heart enlargement (vertebral heart score, 12.1). Two-dimensional echocardiography disclosed right atrial and right ventricular dilatation (Fig 1). An abnormal vascular structure connected to the right atrium at the heart base was observed on color Doppler echocardiography (Fig 2). No other structural heart disease or conditions that could result in right heart dilatation (eg, pulmonary hypertension, atrial septal defect [ASD], tricuspid valve regurgitation) were found. A complete blood count (CBC) and serum biochemistry profile were within normal limits. D-dimer concentration (reference range, <0.2 lg/mL) was normal. Computed tomography angiography (CTA) and cardiac catheterization were performed under general anesthesia, maintained by fentanyl constant rate infusion and isoflurane inhalation, to determine a definitive diagnosis. A 4 Fr multipurpose catheter was introduced from the right jugular vein through a catheter introducer placed by the Seldinger technique. Oxygen saturation (SaO2) of each site within the heart was measured while breathing room air. Mean SaO2 of the cranial and caudal vena cava was 55.9%. SaO2 in the right atrium varied from 81.8 to 99.2%, depending on the location of the catheter tip. SaO2 at the right ventricle and pulmonary artery were 77.0 and 83.2%, respectively. Mean right atrial and pulmonary pressures were 1 and 11 mmHg, respectively. The dog was placed in dorsal recumbency on a clinical 16-multi-detector-row computed tomography scanner. Iodinated contrast medium (2 mg/kg) was rapidly injected via the cephalic vein. Repetitive transverse plane cine scans (120 kV, 99 mAs, 0.625 mm slice thickness, 0.6 s tube rotation time, 0.938 helical pitch) were acquired over the heart. Images were transferred to an image software system for further evaluation. Acquired images were analyzed using multiplanar reconstruction and volume rendering, and it was determined that the pulmonary vein of the right cranial lung lobe was connected to the right atrium. Therefore, a definitive diagnosis of partial anomalous pulmonary venous connection (PAPVC) was made (Fig 3).

Efficacy and safety of tranexamic acid as an emetic in dogs

OBJECTIVE To determine dose dependency of tranexamic acid-induced emesis and the time course of the antifibrinolytic potency of tranexamic acid in dogs. ANIMALS 10 Beagles. PROCEDURES In a dose-escalating experiment, ascending doses of tranexamic acid (10, 20, and 30 mg/kg, IV) were administered at 5-minute intervals until vomiting was observed. In a separate single-dose experiment, ascending doses of tranexamic acid (20, 30, 40, and 50 mg/kg, IV) were administered at 1-week intervals until vomiting was observed. Time to onset of vomiting and number of vomiting episodes were measured in both experiments. In a coagulation experiment, a single 50 mg/kg bolus of tranexamic acid was administered, and blood was obtained 1 hour before and 20 minutes, 3 hours, and 24 hours after administration. Antifibrinolytic potency of tranexamic acid was evaluated by use of a modified rotational thromboelastography method. RESULTS Tranexamic acid induced vomiting in a dose-dependent manner. Vomiting frequency was ≤ 2 episodes, and vomiting concluded ≤ 250 seconds after administration. Antifibrinolytic potency of tranexamic acid was significantly higher at 20 minutes following administration, but not different by 24 hours, when compared with the potency measured before administration. No adverse effects were observed in any experiment. CONCLUSIONS AND CLINICAL RELEVANCE IV administration of tranexamic acid induced emesis in a dose-dependent manner. The antifibrinolytic potency of tranexamic acid decreased in a time-dependent manner and was resolved ≤ 24 hours after administration. Further studies are warranted to investigate the emetic and other adverse effects of tranexamic acid in dogs of various breeds and ages.

Prevalence of Patent Foramen Ovale with Right‐to‐Left Shunting in Dogs with Pulmonic Stenosis

BACKGROUND Right-to-left (R-L) shunt caused by patent foramen ovale (PFO) concurrent with pulmonic stenosis (PS) is considered common, although there is a lack of published evidence. OBJECTIVES To investigate the prevalence of R-L shunt caused by a PFO in dogs with PS. ANIMALS Thirty-one client-owned dogs with PS, without obvious extracardiac disease detected on the clinical examinations. METHODS Case control study: R-L shunt probably caused by PFO was diagnosed when IV injected microbubbles appeared at the left atrial level with an intact atrial septum on echocardiography (bubble-positive dogs). The severity of PS concurrent tricuspid regurgitation (TR), relative thickness of the right ventricle, and relative right atrial area were compared between bubble-positive and bubble-negative dogs. RESULTS The prevalence of R-L shunts caused by PFO was 39% (12 of 31 cases). The instantaneous pressure gradient (PG) across the pulmonic valve and relative thickness of the right ventricle were significantly increased in bubble-positive compared with those in bubble-negative dogs. None of the dogs with mild or moderate PS (pressure gradient < 80 mm Hg, n = 2) demonstrated R-L shunt. The prevalence of TR in bubble-positive dogs was significantly higher than that in bubble-negative dogs. DISCUSSION AND CLINICAL RELEVANCE: Patent foramen ovale PFO with R-L shunt was more common in dogs with very severe PS and absent in dogs with mild PS.

Influence of alterations in heart rate on left ventricular echocardiographic measurements in healthy cats.

Objectives The purpose of this study was to evaluate the effect of sudden alterations in heart rate (HR) on left ventricular (LV) wall thickness and dimensions determined by echocardiography in healthy cats. Methods Six experimental cats were used. All cats were anaesthetised and HR was controlled with right atrial pacing. The interventricular septum and left ventricular free wall thickness at end diastole (IVSd and LVFWd, respectively), left ventricular end-diastolic and end-systolic diameter (LVIDd and LVIDs, respectively) and shortening fraction (FS) of each cat were assessed using echocardiography at pacing rates of 120, 130, 140, 150, 160, 170 and 180 ppm. Results There were significant relationships between HR and IVSd, LVFWd, LVIDd, LVIDs and FS. As the HR increased, LV wall thickness increased and chamber dimensions got smaller in a linear fashion. The maximum and minimum differences in wall thickness between 120 ppm and 180 ppm were 2.0 mm and 0.7 mm in single measurements, respectively. Conclusions and relevance LV wall thickness and dimensions were significantly influenced by alterations in HR.

Restenosis after balloon valvuloplasty in a dog with pulmonary stenosis

A two-month-old female Chihuahua was diagnosed as severe pulmonary valvular stenosis (PS). Although balloon valvuloplasty (BV) was successfully performed, restenosis was observed 19 months after the procedure. Euthanasia was chosen due to low output syndrome during the surgical repair attempted when the dog was 5 years old. Postmortem examination revealed markedly thickened pulmonary valve due to the increase of extracellular matrix which might be produced by increased α smooth muscle actin-positive myofibroblasts. The thickening of the valve was associated with restriction of the valve’s motion, resulting in restenosis in the present case. This is the first case report documented histopathological and immunohistochemical findings of the restenotic pulmonary valve in dogs with PS after BV.

Pharmacodynamics of alacepril in healthy cats

Objectives The aims of this study were to investigate the pharmacodynamics of alacepril and to determine the appropriate dose for clinical usage in cats. Methods Six experimental cats were used. Each cat received alacepril orally at a single dose of 1 mg/kg, 2 mg/kg and 3 mg/kg. Blood samples were collected before administration and at 2, 4, 6, 8, 12, 24, 36, 48 and 72 h after administration to measure serum angiotensin converting enzyme (ACE) activity. Systolic blood pressure was also measured at the same time point. Results Dose-dependent inhibition of ACE activity was observed. Doses of 2 mg/kg and 3 mg/kg alacepril were considered to effectively inhibit ACE activity. There were no significant differences in systolic blood pressue among groups at any time point. Conclusions and relevance Alacepril 2–3 mg/kg q24h may be an appropriate dosage for clinical use in cats.