Publications by authors named "Yoshihisa Yamane"

43 Publications

Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance.

Am J Physiol Heart Circ Physiol 2018 06 16;314(6):H1192-H1202. Epub 2018 Feb 16.

Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University , Tokyo , Japan.

Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca sensitivity of muscle contraction. We have previously shown that a heart-specific myosin light chain phosphatase small subunit (hHS-M) increases the Ca sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M in vivo and the causative role of abnormal Ca sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M. We confirmed that hHS-M increased the Ca sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M transgenic mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase inhibitor fasudil. Our findings suggested that the overexpression of hHS-M results in cardiac dysfunction and conduction disturbance via non-myosin light chain 2 phosphorylation-dependent regulation. NEW & NOTEWORTHY The present study is the first to develop mice with transgenic overexpression of a heart-specific myosin light chain phosphatase small subunit (hHS-M) and to examine the effects of hHS-M on cardiac function. Elevation of hHS-M induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00696.2017DOI Listing
June 2018

Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease.

Nucleic Acids Res 2018 02;46(4):1565-1583

Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Modified uridine containing taurine, 5-taurinomethyluridine (τm5U), is found at the anticodon first position of mitochondrial (mt-)transfer RNAs (tRNAs). Previously, we reported that τm5U is absent in mt-tRNAs with pathogenic mutations associated with mitochondrial diseases. However, biogenesis and physiological role of τm5U remained elusive. Here, we elucidated τm5U biogenesis by confirming that 5,10-methylene-tetrahydrofolate and taurine are metabolic substrates for τm5U formation catalyzed by MTO1 and GTPBP3. GTPBP3-knockout cells exhibited respiratory defects and reduced mitochondrial translation. Very little τm5U34 was detected in patient's cells with the GTPBP3 mutation, demonstrating that lack of τm5U results in pathological consequences. Taurine starvation resulted in downregulation of τm5U frequency in cultured cells and animal tissues (cat liver and flatfish). Strikingly, 5-carboxymethylaminomethyluridine (cmnm5U), in which the taurine moiety of τm5U is replaced with glycine, was detected in mt-tRNAs from taurine-depleted cells. These results indicate that tRNA modifications are dynamically regulated via sensing of intracellular metabolites under physiological condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gky068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829720PMC
February 2018

Nuclear accumulation of androgen receptor in gender difference of dilated cardiomyopathy due to lamin A/C mutations.

Cardiovasc Res 2013 Aug 30;99(3):382-94. Epub 2013 Apr 30.

Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Bunkyo-Ku, Tokyo 113-8510, Japan.

Aims: Dilated cardiomyopathy (DCM) is characterized by ventricular dilation associated with systolic dysfunction, which could be caused by mutations in lamina/C gene (LMNA). LMNA-linked DCM is severe in males in both human patients and a knock-in mouse model carrying a homozygous p.H222P mutation (LmnaH222P/H222P). The aim of this study was to investigate the molecular mechanisms underlying the gender difference of LMNA-linked DCM.

Methods And Results: A whole-exome analysis of a multiplex family with DCM exhibiting the gender difference revealed a DCM-linked LMNA mutation, p.R225X. Immunohistochemical analyses of neonatal rat cardiomyocytes expressing mutant LMNA constructs and heart samples from the LMNA-linked DCM patients and LmnaH222P/H222P mice demonstrated a nuclear accumulation of androgen receptor (AR) and its co-activators, serum response factor, and four-and-a-half LIM protein-2. Role of sex hormones in the gender difference was investigated in vivo using the LmnaH222P/H222P mice, where male and female mice were castrated and ovariectomized, respectively, or treated with testosterone or an antagonist of AR. Examination of the mice by echocardiography, followed by the analyses of histological changes and gene/protein expression profiles in the hearts, confirmed the involvement of testicular hormone in the disease progression and enhanced cardiac remodelling in the LmnaH222P/H222P mice.

Conclusion: These observations indicated that nuclear accumulation of AR was associated with the gender difference in LMNA-linked DCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvt106DOI Listing
August 2013

Extreme tetralogy of Fallot in a dog.

J Vet Med Sci 2013 5;75(8):1111-4. Epub 2013 Apr 5.

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.

A four-month-old female Labrador retriever was brought to the Tokyo University of Agriculture and Technology Animal Medical Center for examination of its main symptoms of cough, tachypnea and exercise intolerance. Upon examination, the dog was found to have cyanosis and inadequate growth. Echocardiography revealed tetralogy of Fallot. Cardiac catheterization confirmed that the main pulmonary artery was completely occluded and that blood flowed from the aorta to the pulmonary artery. Accordingly, the animal was diagnosed with extreme tetralogy of Fallot.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.12-0319DOI Listing
April 2014

Predicting metastatic potential of gastrointestinal stromal tumors in dog by ultrasonography.

J Vet Med Sci 2012 Nov 8;74(11):1477-82. Epub 2012 Jun 8.

Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.

Gastrointestinal stromal tumor (GIST), a mesenchymal neoplasm affecting the gastrointestinal tract, shows a variety of clinical behaviors from inactive benign to aggressive malignant in dogs. In this study, the feasibility of using clinically significant ultrasonographic features to predict the metastatic potential of canine GIST was investigated through comparison with actual metastatic incidence and findings of malignancy obtained by postoperative pathological examination. Ultrasonographic features, including large tumor size, irregular margin and heterogeneous internal echogenicity with large hypoechoic areas, related closely with the presence of metastasis as well as a high-risk ranking by the human classification system according to pathological findings. Based on these ultrasonographic features, the potential of metastasis in canine GIST could be preoperatively predicted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.11-0553DOI Listing
November 2012

Efficacy and safety of firocoxib for the treatment of pain associated with soft tissue surgery in dogs under field conditions in Japan.

J Vet Med Sci 2012 Oct 31;74(10):1283-9. Epub 2012 May 31.

Merial Japan, Tokyo Opera City Tower, 3-20-2 Nishi Shinjuku, Shinjuku, Tokyo, Japan.

Use of firocoxib in dogs for postoperative pain control has not been published in any of the journals in Japan. A field study was conducted to evaluate the efficacy and safety of firocoxib in dogs in controlling pain associated with soft tissue surgery in Japan. The study followed a negative control, double-blind, multicenter clinical efficacy study using a randomized block design. A total of 131 client-owned dogs presented to the clinical practices for soft tissue surgery were enrolled. Sixty-nine dogs were allocated to the firocoxib-treated group and received 5 mg/kg of firocoxib orally on Day 0 before the surgery and once daily through Day 2, while 62 dogs were allocated to the non-treated group handled in a similar manner only without the firocoxib administration. Pain assessment took place on Day 0 before the surgery through Day 2. The primary efficacy variable was a success/failure variable based on whether the dog needed rescue medication (based on pain assessment after the surgery or Investigator's judgment) and a significant difference between firocoxib-treated group (16.4%) and non-treated group (50.0%) (P=0.0031) was observed. There was no adverse event during the study that was considered to be related to the administration of firocoxib. This study indicated the clinical efficacy and safety profile of firocoxib administered to control pain associated with soft tissue surgery under field condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.11-0306DOI Listing
October 2012

Epidemiological and morphological studies of double-chambered right ventricle in dogs.

J Vet Med Sci 2011 Oct 7;73(10):1287-93. Epub 2011 Jun 7.

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.

The double-chambered right ventricle (DCRV) is a rare congenital cardiac disease in dogs, and its detailed epidemiological and morphological features are not clearly understood. By investigating the profile, clinical signs, and characteristics of examination findings of eleven dogs with DCRV by means of a retrospective study, we attempted to clarify the epidemiology and morphology of the condition. The study group consisted of nine males and two females. Breeds included Pug (n=3), Miniature Dachshund (n=1), French Bull-dog (n=1), Shiba (n=1), and Retrievers (n=5). The attachment site of the anomalous muscular bundle was continuous with the cardiac apex in nine dogs, and it was attached to the right ventricle free wall in the other two dogs. In dogs with DCRV, at least one of the following conditions was present concurrently: congenital or acquired tricuspid valve regurgitation (TR), ventricular septal defect, and atrial septal defect. Also, the pressure difference between the two chambers increased over time, and progressive right-sided heart failure was observed. In summary, DCRV occurs in small breeds of dog as well as in large breeds of dog and it may be more prevalent in males. The existence of two types of DCRV in dogs was established. Dog with DCRVs will have a high incidence of concurrent cardiac abnormalities. Concurrent TR may be either congenital or acquired. DCRV is a congenital disorder, but the clinical condition progresses as the dog develops.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.10-0485DOI Listing
October 2011

Effects of enfonidipine hydrochloride in dogs with experimental supraventricular tachyarrhythmia.

J Vet Med Sci 2010 Jul 23;72(7):833-8. Epub 2010 Feb 23.

Laboratory of Veterinary Surgery, Tokyo University of Agriculture and Technology, Tokyo, Japan.

It is required not to increase the ventricular rate and to preserve the ventricular systolic function in treating supraventricular tachyarrhythmia (SVTA). The objective of this study is to investigate whether or not Efonidipine hydrochloride (EH), a T and L dual type Ca(2+) channel blocker, suppresses the increasing ventricular rate without reducing the ventricular systolic function using canine SVTA models by rapid atrial pacing (RAP) method. Clinically healthy fourteen beagles were used. The 14 dogs were randomly assigned to the EH-administered group (EH group, n=7) and non-EH-administered group (control group, n=7). The EH group was orally-administered EH at 5 mg/kg SID during RAP. On the other hand, the control group was applied RAP without oral administration of EH. Duration of RAP was for 3 weeks for both groups. The ventricular rate for the EH group was significantly lower than that for the control group. The left ventricular- fractional shortening for the control group declined significantly compared to baseline. Those for the EH group did not show any changes over time and were significantly higher than the control group. The ratio between pre-ejection period and ejection for the EH group were significantly lower than those of the control group. In conclusion, the study demonstrated that EH suppresses the increasing ventricular rate without reducing the ventricular systolic function in canine SVTA model. Therefore, EH is expected to become a new treatment for canine SVTA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.09-0358DOI Listing
July 2010

Purulent pericarditis in a dog administered immune-suppressing drugs.

J Vet Med Sci 2009 May;71(5):669-72

Animal Clinical Research Foundation, Tottori, Japan.

A 5-year-old castrated mongrel dog was brought to our hospital with anorexia and vomiting. Laboratory testing revealed immune-mediated hemolytic anemia (IMHA), and so treatment was initiated with multiple immune-suppressing drugs, achieving partial remission from IMHA. However, cardiac tamponade due to purulent pericarditis was identified as a secondary disease. Culture of pericardial fluid yielded numerous Candida albicans and multidrug-resistant Acinetobacter sp. Pericardiocentesis was performed, and the condition of the dog improved. However, the dog died the next day.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.71.669DOI Listing
May 2009

Effect of beraprost sodium (BPS) in a new rat partial unilateral ureteral obstruction model.

Prostaglandins Leukot Essent Fatty Acids 2009 May-Jun;80(5-6):263-7. Epub 2009 May 23.

Takenaka Animal Hospital, 3-10-3 Zao-cho, Fukuyama, Hiroshima 721-0971, Japan.

Unilateral ureteral obstruction (UUO) is a representative model for investigating the common mechanism of decreasing renal function in chronic renal failure. In this study, we present a new partial UUO model in adult rats and evaluated the effect of beraprost sodium (BPS: stable prostaglandin I(2) (PGI(2)) analog). We could make reproductive and uniform partial UUO by ligating the left ureter together with a 0.5 mm diameter stainless steel wire with nylon thread, and withdrawing the stainless wire. One week later, the ureteral obstruction was released. After 3 weeks from the release of UUO, all animals of control group, without BPS administration, developed basophilic degeneration of tubular epithelium, tubular dilatation and interstitial fibrosis. The areas of tubular degeneration and fibrosis were significantly reduced in the BPS group, orally administered BPS 300 microg/kg twice a day from the next day of the release of obstruction, than in control group. In conclusion, we can established the adult rat partial UUO-release model and revealed that BPS can inhibit renal tubular damage and tubulointerstitial fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plefa.2009.03.002DOI Listing
September 2009

Cardiovascular effects of right ventricle-pulmonary artery valved conduit implantation in experimental pulmonic stenosis.

J Vet Med Sci 2009 Apr;71(4):477-83

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.

Right ventricle (RV)-pulmonary artery (PA) valved conduit (RPVC) implantation decreases RV systolic pressure in pulmonic stenosis (PS) by forming a bypass route between the RV and the PA. The present study evaluates valved conduits derived from canine aortae in a canine model of PS produced by pulmonary artery banding (PAB). Pulmonary stenosis was elicited using PAB in 10 conditioned beagles aged 8 months. Twelve weeks after PAB, the dogs were assigned to one group that did not undergo surgical intervention and another that underwent RPVC using denacol-treated canine aortic valved grafts (PAB+RPVC). Twelve weeks later, the rate of change in the RV-PA systolic pressure gradient was significantly decreased in the PAB+RPVC, compared with the PAB group (60.5 +/- 16.7% vs. 108.9 +/- 22.9%; p<0.01). In addition, the end-diastolic RV free wall thickness (RVFWd) was significantly reduced in the PAB+RPVC, compared with the PAB group (8.2 +/- 0.2 vs. 9.4 +/- 0.7 mm; p<0.05). Thereafter, regurgitation was not evident beyond the conduit valve and the decrease in RV pressure overload induced by RPVC was confirmed. The present results indicate that RPVC can be performed under a beating heart without cardiopulmonary bypass and adapted to dogs with various types of PS, including "supra valvular" PS or PS accompanied by dysplasia of the pulmonary valve. Therefore, we consider that this method is useful for treating PS in small animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.71.477DOI Listing
April 2009

Histological study of right ventricle-pulmonary artery valved conduit implantation (RPVC) in dogs with pulmonic stenosis.

J Vet Med Sci 2009 Apr;71(4):409-15

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyTokyo, Japan.

We examined whether right ventricle-pulmonary artery valved conduit (RPVC) implantation can overcome the disadvantages of current procedures for pulmonic stenosis (PS). We histologically evaluated the feasibility of RPVC using a homograft in PS model dogs. Eight dogs underwent pulmonary artery banding (PAB) and then 12 weeks later were assigned to PAB (n=4) or PAB+RPVC (n=4) groups. Dogs in the PAB group received no treatment throughout the experimental period, whereas the PAB+RPVC group underwent RPVC. At 1 year after PAB, hearts and conduits were explanted from euthanized dogs and histologically evaluated. The ratios (%) of myocardial fibrosis on right ventricle (RV) epicardial, median and endocardial layers were significantly lower in the PAB+RPVC, than in the PAB group. The ratio of myocardial fibrosis on left ventricular (LV) epicardial and endocardial layers were significantly lower in the PAB+RPVC, than in the PAB group. Neo-intimal thickness in the anastomosis areas of the Denacol and PAB+RPVC groups was 42.77 +/- 30.19 and 88.30 +/- 27.24 microm, respectively, with no significant differences between the groups. Calcification and neo- intima hypertrophy were not obvious in the valve area. Immunohistological staining showed that the internal surface of the anastomosis and intermediate areas were positive for endothelial cells. We concluded that RPVC using a bioprosthetic graft can apparently overcome the disadvantages of current procedures for pulmonic stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.71.409DOI Listing
April 2009

Successful surgical correction of supravalvular pulmonary stenosis under beating heart using a cardiopulmonary bypass system in a dog.

J Vet Med Sci 2009 Feb;71(2):203-6

Department of Veterinary Surgery, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.

A male Pomeranian dog aged 1 year and 8 months was presented for evaluation of severe systolic ejection, cardiac murmur and syncope on excitation. Supravalvular pulmonary stenosis was diagnosed. An echocardiogram showed a supravalvular membranous stricture and a severely increased pulmonary arterial velocity in the stricture (6.49 m/s, pressure gradient of 169 mmHg). The supravalvular stricture was surgically removed by pulmonary arteriotomy with the heart beating using a cardiopulmonary bypass system. The postoperative pulmonary arterial velocity at the narrow area decreased to 3.80 m/s, and the pressure gradient decreased to 57.7 mmHg. Six months after the operation, there were no signs of restenosis, and the dog was in good condition without syncope. Surgical correction of pulmonary stenosis with the heart beating using a cardiopulmonary bypass system is useful because of the improvement it brings in safety and reliability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.71.203DOI Listing
February 2009

Hydrodynamic characteristics of porcine aortic valves cross-linked with glutaraldehyde and polyepoxy compounds.

ASAIO J 2009 Jan-Feb;55(1):13-8

Faculty of Agriculture, Department of Veterinary Surgery, Tokyo University of Agriculture and Technology, Saiwai-cho, Fuchu-shi, Tokyo, Japan.

Porcine aortic valve (AoF) tissues cross-linked with glutaraldehyde and epoxy compounds were reported to have high anticalcification properties, but their hydrodynamic characteristics have not been evaluated. The aim of the present study was to investigate the hydrodynamic differences between porcine AoFs, cross-linked with concomitant use of an epoxy compound and glutaraldehyde, at different fixation periods. The valves were mounted on a pulsatile flow circulation mimicking a left heart. The left atrial and left ventricular pressures and mitral and aortic flows were measured at every 0.002 seconds, and the hydrodynamic factor of the valves mounted on the mitral position was estimated. Effective orifice area and the regurgitation volume, which are used as indicators of valve efficiency, failed to detect significant differences due to glutaraldehyde fixation time. In addition, the pressure gradient across the bioprosthetic valve and the variation of mitral flow also had no significant differences. The flow circuit model of the present study was mimicking of a left heart. The evaluation of the mitral valvular function with different glutaraldehyde fixation times was accomplished by relating the pressure with the flow, and by estimating the time lag between valve motion and transvalvular flow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0b013e31818f2880DOI Listing
March 2009

Effects of beta-blocker on left ventricular remodeling in rats with volume overload cardiac failure.

J Vet Med Sci 2008 Nov;70(11):1231-7

Department of Veterinary Clinical Oncology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.

The beneficial effects of beta-blockers on left ventricular (LV) remodeling have been reported in association with several conditions that cause heart failure, but their effects on the volume overloaded heart failure have not been well defined. Fifty Wistar rats that survived aortocaval (AC) shunt creation were randomly allotted into the following two groups: untreated animals (ACS; n=26) and animals treated with 100 mg/kg/day metoprolol (MP; ACS+MP; n=24). The effects of MP were evaluated at 1, 4 and 12 weeks post-surgery through echocardiographic, hemodynamic and pathologic studies. At 12 weeks post-surgery, LV wall thinning associated with chamber dilatation was observed in ACS but not in ACS+MP. LV end-diastolic pressure and diastolic wall stress were lower in ACS+MP than in ACS. The increase in LV weight was similar in both ACS and ACS+MP at 1 and 4 weeks post-surgery, but at 12 weeks post-surgery, it was significantly greater in ACS+MP than in ACS. At the cellular level, although the cardiac myocyte length progressively increased to a similar extent in both groups, the mean cross-sectional diameter of these cells in ACS+MP was greater than in ACS. In conclusion, MP did not prevent early eccentric hypertrophy in response to volume overload. However, in the late phase of volume overload-induced heart failure, MP appears to allow for myocyte cross-sectional growth and thus prevents LV wall thinning, resulting in a net increase in LV mass. In this manner, MP might contribute to reduction of diastolic wall stress and thereby delay progression of heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.70.1231DOI Listing
November 2008

Long-term clinical evaluation of mitral valve replacement with porcine bioprosthetic valves in dogs.

J Vet Med Sci 2008 Mar;70(3):279-83

Animal Clinical Research Foundation, Kurayoshi, Tottori, Japan.

This study evaluated the long-term clinical performance of newly developed porcine bioprosthetic valves cross-linked with glutaraldehyde and polyepoxy compound for mitral valve replacement (MVR) in dogs. Five beagle dogs underwent MVR using the porcine bioprosthetic valves during cardiopulmonary bypass. Antithrombotic drugs were administered only for one month after MVR. Six months after MVR, transvalvular regurgitation was not observed in all dogs, paravalvular leakage was seen only in one dog. Twelve months after MVR, mild transvalvular regurgitations were observed in two dogs. Although diastolic atrioventricular pressure gradient was increased gradually, no significant differences were observed. Pressure half-time and valve area were within normal ranges as the bioprosthetic value. There was no clinical symptom of the thrombosis and the thrombogenesis was not observed in the porcine bioprosthetic valve and the annulus in all dogs for twelve months after MVR. The clinical findings suggest that antithrombogenicity of the valves were maintained, though the duability might not be enough in the long-term period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.70.279DOI Listing
March 2008

Effect of long-term administration of a prostacyclin analogue (beraprost sodium) on myocardial fibrosis in Dahl rats.

J Vet Med Sci 2007 Dec;69(12):1271-6

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Saiwai-cho, Tokyo, Japan.

Beraprost sodium (BPS) is an orally active prostacyclin analogue. The effects of BPS on the heart, including coronary circulation improvement, myocardial and vascular protection and anti-fibrosis effect on myocardium interstitium, have previously been demonstrated. However, the effects of BPS on hemodynamics, cardiac function and myocardial contractility in patients in the hypertrophic phase have not been clarified. Therefore, in the present study, the effects of BPS under long-term administration were investigated using the hypertension model of salt-sensitive Dahl rats. Six-week-old Dahl rats were divided into three groups, an 8% high salt diet group treated with BPS (BPS group), an untreated 8% high salt diet group (HHF group) and an untreated 0.3% low salt diet group (Control group), and observations were conducted until 17 weeks of age. In the BPS and HHF groups, the survival rates after 11 weeks of high salt diet intake were 87.5% and 47.1%, respectively (p<0.05). At 17 weeks of age, the atrial systolic peak velocity/early diastolic peak velocity and heart weight index of the BPS group decreased significantly compared with the HHF group (p<0.05). The HHF group exhibited significantly more severe myocardial fibrosis mainly in the endocardial layer of the left and right ventricles compared with the BPS and Control groups (p<0.05). In the present study, long-term BPS administration preserved diastolic function and prevented myocardial interstitial fibrosis in the non-compensatory phase. The results of the present study suggest that BPS is effective for treatment of hypertensive cardiac hypertrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.69.1271DOI Listing
December 2007

Evaluation of the efficacy and safety of coil occlusion for patent ductus arteriosus in dogs.

J Vet Med Sci 2007 Aug;69(8):857-9

Veterinary Surgery, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.

We performed a retrospective study of 56 dogs with Patent Ductus Arteriosus (PDA) to evaluate the indications for and efficacy of transarterial PDA coil embolization. Transarterial PDA coil embolization was conducted in 37 cases (66.1%) and surgical ligation was conducted in 16 cases (28.6%). Three cases (5.4%) were diagnosed as pulmonary hypertension and were excluded from surgical intervention. Although coil dislodgement was observed in the pulmonary artery in one case, no death occurred during coil embolization or surgical ligation. Echocardiography showed that fractional shortening decreased from 35.4 +/- 6.8% to 30.2 +/- 5.9% (P<0.05) after transarterial PDA coil embolization. Although slight residual shunts were observed in 18 cases, transarterial PDA coil embolization was effective treatment of PDA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.69.857DOI Listing
August 2007

Short-term performance of mitral valve replacement with porcine bioprosthetic valves in dogs.

J Vet Med Sci 2007 Aug;69(8):793-8

Animal Clinical Research Foundation, 214-10 Yatsuya, Kurayoshi, Tottori 682-0025, Japan.

Porcine bioprosthetic valves cross-linked with glutaraldehyde and polyepoxy compound were newly developed for mitral valve replacement (MVR) in dogs. Five beagle dogs were performed a left thoracotomy and underwent MVR using the porcine bioprosthetic valves during cardiopulmonary bypass (CPB). A vein catheter inserted into right atrium and a vent catheter inserted into the right ventricle to drain. The hemodynamic conditions of CPB were excellent during surgery. The left atrial pressure was measured before and after MVR; there was no significant difference and it was normal. Thrombosis and the prosthetic valve regurgitation were not observed one week after MVR. Pressure half time (PHT) prolonged significantly (P<0.05) from 31.40 +/- 4.0 msec presurgery to 99.20 +/- 19.4 msec at seven days after MVR, although it indicated the normal range as the bioprosthetic valve. The symptom of the prosthetic valve failure was not observed. This study indicated that the MVR using porcine bioprosthetic valves under CPB might have been effective in dogs as a short-term evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.69.793DOI Listing
August 2007

Surgical correction of pulmonic stenosis using transventricular pulmonic dilation valvuloplasty (Brock) in a dog.

J Vet Med Sci 2007 Apr;69(4):437-9

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Japan.

A two-month-old male long coated Chihuahua, which had symptoms including anorexia and decreased growth, was diagnosed with pulmonic valvular stenosis. Echocardiography showed the severe progression of pulmonary arterial velocity (6.29 m/s, Pressure gradient (PG); 158 mmHg). Transventricular pulmonic dilation valvuloplasty (Brock) was conducted, and stenosed valve was dilated by the oto forceps. Pleural effusion was observed postoperatively, however, it was diminished under the intensive care for five days after the surgery. The right ventricular systolic pressure was decreased to 60 mmHg in angiocardiography conducted two months postoperatively and the dog has kept a good general condition with recovered vigor and appetite.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.69.437DOI Listing
April 2007

Chronic effect of transrectal split-focus ultrasonic ablation on canine prostatic tissue.

J Vet Med Sci 2006 Aug;68(8):839-45

Central Research Laboratory, Hitachi, Ltd, Kokubunji, Tokyo, Japan.

The treatment time needed for high-intensity focused ultrasound (HIFU) ablation might be decreased substantially by using the split-focus approach, so we made a prototype 4.2-MHz split-focus therapeutic transducer combined with a small 6.5-MHz imaging ultrasonic probe for transrectally treatment of canine prostatic cancer and used it to experimentally evaluate the feasibility of using split-focus transrectal HIFU to ablate canine prostatic tissue without injuring surrounding tissues. The prostates of 5 dogs were transrectally treated with split-focus ablation at a peak intensity in the water of 1.7 kW/cm(2) for 4 s (4 shots) under the guidance of ultrasonic B-mode imaging. After ultrasonic exposure, the prostates became stiff because of thermal effect of HIFU. For the first 3-5 days after treatment, dogs were catheterized daily for urinary management and treated with oral antibiotics to prevent urinary tract infection. The dogs were able to urinate normally by a week after. Within two weeks a large centrally located cystic cavity had formed in the prostate by replacing the necrotic parenchyma around the prostatic urethra. Necropsy three months after treatment found the rectum and prostate capsule to be normal grossly and histologically. The 4 shots of split-focus HIFU destroyed the prostatic parenchyma and created a prostatic cavity 0.34-0.45 cm(3) in volume without injuring surrounding tissues. These results suggest that split-focus HIFU ablation could be used for noninvasive treatment of prostatic cancer in dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.68.839DOI Listing
August 2006

Comparison of right atrium incision and right ventricular outflow incision for surgical repair of membranous ventricular septal defect using cardiopulmonary bypass in dogs.

Vet Surg 2006 Jun;35(4):382-7

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Objective: To compare right atrium incision (RAI) and right ventricular outflow incisions (RVI) for surgical repair of membranous ventricular septal defect (VSD) facilitated by cardiopulmonary bypass (CPB).

Study Design: Retrospective study.

Animals: Dogs (n=10) with VSD.

Methods: Medical records of dogs that had VSD repair were reviewed. Membranous VSD without any malformation and abnormality was confirmed on several clinical examinations and by angiocardiography. RAI (5 dogs) and RVI (5 dogs) was used for VSD access and repair facilitated by CPB. Procedure comparison was by surgical duration, postoperative recovery period, and occurrence of postoperative arrhythmia.

Results: Duration of surgery was similar for RAI and RVI; however, postoperative recovery time was significantly reduced with RAI. Significant moderate operative damage occurred with right atrium incision.

Conclusions: Right atrium incision was more effective than RVI for repair of membranous VSD using CPB.

Clinical Relevance: RAI should be considered in preference to RVI for repair of membranous VSD using CPB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1532-950X.2006.00161.xDOI Listing
June 2006

Cardiac remodeling and angiotensin II-forming enzyme activity of the left ventricle in hamsters with chronic pressure overload induced by ascending aortic stenosis.

J Vet Med Sci 2006 Mar;68(3):271-6

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchushi, Tokyo 183-0054, Japan.

Cardiac remodeling and angiotensin II-forming enzyme activity of the left ventricle on chronic pressure overload were studied in male Syrian hamsters, whose chymase activity is similar to that of dogs. Pressure overload was achieved by banding at the ascending aorta (aortic stenosis). Echocardiography, histological analysis, and analysis of cardiac angiotensin-converting enzyme and chymase-like activities were performed. At 10 weeks after banding, concentric hypertrophy of the left ventricle was evident. At 20 weeks after banding, the ventricular weight-to-body ratio, cardiac fibrosis, and cardiac chymase-like activity were significantly increased, while cardiac angiotensin-converting enzyme activity was significantly decreased. This suggests that cardiac chymase, compared with cardiac angiotensin-converting enzyme, was activated against the chronic pressure overload and was responsible for the cardiac remodeling through the formation of angiotensin II. Considering the utility of the rodents, the interspecies similarity of the Ang II-forming pathway, and the effect of chymase in the hamsters, the present model is considered useful for studies evaluating the effect of Ang II and chymase in the canine heart with chronic pressure overload.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.68.271DOI Listing
March 2006

Effect of Angiotensin II Type 1 receptor blocker on cardiac angiotensin-converting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters.

J Vet Med Sci 2006 Mar;68(3):227-33

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchushi, Tokyo 183-0054, Japan.

It has been reported that cardiac chymase has an effect on cardiac fibrosis through the Angiotensin (Ang) II formation and an Ang II-independent mechanism. In the present study, Ang II type 1 (AT1) receptor blocker (candesartan cilexetil) was administered to dilated cardiomyopathic (DCM; Bio TO2) hamsters for 4 weeks to study the effect of AT1 receptor blocker on cardiac chymase-like activity and cardiac fibrosis. Echocardiography, histological examination, and assessment of cardiac angiotensin-converting enzyme (ACE)/chymase-like activities were conducted. Hamsters showed cardiac dysfunction due to increased left ventricular dimensions and decreased ventricular wall thickness, significant increase in cardiac chymase-like activity, and fibrosis. This result indicates that the cardiac chymase-like activity is responsible for cardiac fibrosis. When candesartan cilexetil was administered to Bio TO2 hamsters, cardiac chymase-like activity increased significantly, whereas cardiac fibrosis decreased significantly. Cardiac ACE and chymase-like activities were unchanged in non-DCM hamsters with candesartan cilexetil. This suggests that the cardiac Ang II formation mechanism was stimulated by suppressing the effect of cardiac Ang II, and cardiac chymase-like activity could be increased. Moreover, this mechanism may be more highly activated if cardiac Ang II is activated in the heart. In conclusion, we demonstrated that AT1 receptor blocker reduced cardiac fibrosis, although cardiac chymase-like activity increased. Because the Ang II-forming pathway and the effect of chymase in hamsters is similar to that in dogs, the results of the present study may supplement the available information for dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.68.227DOI Listing
March 2006

Effect of intermittent administration of sustained release isosorbide dinitrate (sr-ISDN) in rats with pressure-overload heart.

J Vet Med Sci 2006 Mar;68(3):213-7

Department of Veterinary Surgery, Faculth of Agriculture, Tokyo University of Agriculture and Technology, Fuchushi, Tokyo 183-8509, Japan.

Recent studies have demonstrated the benefits of nitric oxide (NO) on myocardial hypertrophy and myocardial fibrosis. It was suggested that NO has a protective effect on myocardial cell through the neurohormonal system. This effect serves to highlight the important role of NO in maintaining the function and form of heart with chronic heart failure. However, there are no known reports about on the effect of prolonged administration of nitrate on pressure over-load heart. This study was conducted to examine the long-term effect of oral nitrate therapy in rats with pressure-overloaded heart. An abdominal aorta constricted (AC) model of pressure-overloaded heart was created in male Wistar rats. Sustained release isosorbide dinitrate (sr-ISDN) (5 mg/kg once a daily) was administered to the rats once a daily for 12 weeks. The animals were euthanized during the study period, and the heart was collected and weighed. Histopathological examination was performed to evaluate the effect of sr-ISDN on myocardial hypertrophy and fibrosis. The ratio of heart to body weight increased significantly in AC rat and this increase was significantly prevented by sr-ISDN treatment. Histopathological examination showed significant increase in fibrotic area of AC rat compared to sham rat, this increase was inhibited by sr-ISDN treatment. Cardiomyocyte transverse diameter was significantly increased in AC rat compared with sham rat, but this increase tended to decrease by sr-ISDN treatment. In conclusion, intermittent administration with sr-ISDN has mild effect in inhibiting cardiac hypertrophy and marked effect in inhibiting fibrosis due to pressure-overload.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.68.213DOI Listing
March 2006

The effect of intermittent administration of sustained release isosorbide dinitrate (sr-ISDN) in rats with volume overload heart.

J Vet Med Sci 2006 Jan;68(1):49-54

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.

Recently, it has been reported that intermittent administration of nitrate, with a nitrate-free interval of 10 to 12 hr eliminated expression of tolerance, and maintained its hypotensive effect. In the present study, we evaluated whether nitrate tolerance developed or not with an intermittent administration of sr-ISDN (5 mg/kg/ once a day) in Wistar rats. The effect of this administration protocol for sr-ISDN on the volume overload heart model, aortovenous fistula, was also examined. Furthermore, blood pressure was monitored by radio telemetry during sr-ISDN (5 mg/kg/once a day) administration. Nitrate tolerance did not develop, and eccentric hypertrophy due to volume overload was moderated by sr-ISDN administration. Sr-ISDN administration maintained blood pressure lower level than the placebo group. In conclusion, prolonged intermittent administration of sr-ISDN maintained its hypotensive effect during the entire experiment period, without developing tolerance, and moderated efferent hypertrophy with attenuated volume overload.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.68.49DOI Listing
January 2006

Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus.

J Vet Med Sci 2005 Oct;67(10):1013-7

Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Morioka, Japan.

Mammary tumors are the most common tumor type in women as well as in female dogs. The BRCA2 gene encodes a large nuclear protein that is involved in DNA repair, and mutations in the human BRCA2 confer an increased risk of female mammary tumors. The BRCA2 protein acts as a tumor suppressor, and inactivation of BRCA2 by loss of heterozygosity is implicated in mammary carcinogenesis. In this study, to establish an appropriate polymorphic marker for loss of heterozygosity analysis of the canine BRCA2, we analyzed the genomic sequences of the exon 27 regions of 30 mammary-tumor-bearing and 21 tumor-free dogs. In addition to 10204ins/delAAA, which is the only polymorphism previously identified for the canine BRCA2 locus, we discovered four novel single nucleotide polymorphisms. The analysis of these five polymorphisms revealed the presence of four allele types. Since 10204ins/delAAA was the most common of the five polymorphisms identified, we developed a PCR-based assay method to assay for this polymorphism. We believe that this method is valuable for loss of heterozygosity analysis of the canine BRCA2 gene in tumor pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.67.1013DOI Listing
October 2005

Megaesophagus was complicated with Billroth I gastroduodenostomy in a cat.

J Vet Med Sci 2005 Sep;67(9):935-7

Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.

A seven-year-old, female, domestic short hair cat was presented with a history of chronic anorexia. Radiographic examination revealed a large space-occupying calcified mass in the abdominal cavity. The mass was located in pylorus and did not extend into the duodenum and surrounding tissues. Billroth I gastroduodenostomy was conducted to remove the mass. Histopathological examination of the mass showed a lymphoma. Although Recovery following the operation was excellent, the patient showed intermittent vomiting unrelated to feeding. Radiographical examination revealed a megaesophagus, which was assumed to be a complication of the Billroth I procedure, since the condition was not observed before the procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.67.935DOI Listing
September 2005

Insertion/deletion polymorphism in the BRCA2 nuclear localization signal.

Biomed Res 2005 Jun;26(3):109-16

Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Morioka 020-8550, Japan.

Mutations in human BRCA2 confer an increased risk of female breast cancer. In this study, we found a novel insertion/deletion polymorphism (10204insAAA causing amino acid change M3332IK) in canine BRCA2, which is located in the putative second nuclear localization signal (NLS2) and C-terminal Rad51-binding region. The nuclear localization of the insAAA C-terminus was more efficient than localization of the delAAA sequence when NLS1 was mutated. Strong, comparable Rad51 binding was observed for both the insAAA and delAAA C-termini. Dogs with the insertion/deletion polymorphism will provide a new model for studying the function of BRCA2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2220/biomedres.26.109DOI Listing
June 2005
-->