RESUMEN
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.
Asunto(s)
ARN de Transferencia/metabolismo , Taurina/deficiencia , Uridina/análogos & derivados , Animales , Proteínas Portadoras/fisiología , Gatos , Preescolar , Femenino , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/fisiología , Células HEK293 , Células HeLa , Humanos , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , ARN de Transferencia/química , Proteínas de Unión al ARN , Uridina/biosíntesisRESUMEN
Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+ sensitivity of muscle contraction. We have previously shown that a heart-specific myosin light chain phosphatase small subunit (hHS-M21) increases the Ca2+ sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M21 in vivo and the causative role of abnormal Ca2+ sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21 increased the Ca2+ sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M21 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-M21 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-M21) and to examine the effects of hHS-M21 on cardiac function. Elevation of hHS-M21 induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias.
Asunto(s)
Arritmias Cardíacas/enzimología , Insuficiencia Cardíaca/enzimología , Miocitos Cardíacos/enzimología , Fosfatasa de Miosina de Cadena Ligera/metabolismo , Animales , Arritmias Cardíacas/genética , Arritmias Cardíacas/patología , Arritmias Cardíacas/fisiopatología , Señalización del Calcio , Miosinas Cardíacas/metabolismo , Cardiomiopatías/enzimología , Cardiomiopatías/genética , Cardiomiopatías/fisiopatología , Modelos Animales de Enfermedad , Fibrosis , Predisposición Genética a la Enfermedad , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca , Humanos , Ratones Endogámicos C57BL , Ratones Transgénicos , Contracción Miocárdica , Miocitos Cardíacos/patología , Cadenas Ligeras de Miosina/metabolismo , Fosfatasa de Miosina de Cadena Ligera/genética , Fenotipo , Fosforilación , Subunidades de Proteína , Regulación hacia Arriba , Disfunción Ventricular Izquierda/enzimología , Disfunción Ventricular Izquierda/genética , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda , Remodelación Ventricular , Quinasas Asociadas a rho/metabolismoRESUMEN
BACKGROUND: "Arterialization" of the dorsal hand vein is well-established in human medicine, but not in veterinary medicine. OBJECTIVES: To compare cephalic and saphenous venous blood collected by continuously heating the paws to 37°C ("arterialization"), with arterial blood (AB) for measurement of blood gas variables in well-perfused dogs. ANIMALS: Eight healthy dogs. METHODS: Experimental study. Fore and hind paws were continuously heated to 37°C to "arterialize" cephalic and saphenous venous blood. AB and "arterialized" cephalic and saphenous venous blood (ACV and ASV, respectively) were simultaneously collected from lightly anesthetized dogs with induced metabolic and respiratory acid-base disorders. The pH, partial pressures of carbon dioxide (PCO2 ) and oxygen (PO2 ), bicarbonate concentration [HCO3 - ], and base excess (BE) were measured once in each state. Systolic blood pressure was maintained above 100 mm Hg. The AB, ACV, and ASV values were compared. RESULTS: The pH, [HCO3 - ], and BE values had no significant difference and good agreement, the PCO2 values had a strong correlation (correlation coefficient of .91-1.00), and the PO2 values had a significant difference (P < .01) and poor agreement between AB and ACV, and between AB and ASV. The PCO2 values of ASV overestimated those of AB by ~3.0 mm Hg, which was considered within clinically allowable limits, while those of ACV were not within clinically allowable limits. CONCLUSIONS AND CLINICAL IMPORTANCE: Under experimental conditions, the ASV samples were more identical to the AB samples than the ACV samples for pH, PCO2 , [HCO3 - ], and BE values in well-perfused dogs. The saphenous vein is suitable for "arterialization."
Asunto(s)
Calefacción , Vena Safena , Animales , Humanos , Perros , Concentración de Iones de Hidrógeno , Análisis de los Gases de la Sangre/veterinaria , Oxígeno , Dióxido de CarbonoRESUMEN
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.
Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , Nitrofenoles/uso terapéutico , Taquicardia Supraventricular/veterinaria , Taquicardia/veterinaria , Animales , Antihipertensivos/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Compuestos Organofosforados/uso terapéutico , Sístole/efectos de los fármacos , Sístole/fisiología , Taquicardia/tratamiento farmacológico , Taquicardia Supraventricular/tratamiento farmacológico , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Cateterismo Cardíaco/veterinaria , Puente Cardiopulmonar/veterinaria , Enfermedades de los Perros/cirugía , Estenosis de la Válvula Pulmonar/veterinaria , Animales , Perros , Ecocardiografía Doppler/veterinaria , Masculino , Estenosis de la Válvula Pulmonar/cirugíaRESUMEN
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.
Asunto(s)
Anemia Hemolítica Autoinmune/veterinaria , Candidiasis/veterinaria , Enfermedades de los Perros/microbiología , Inmunosupresores/efectos adversos , Pericarditis/veterinaria , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anemia Hemolítica Autoinmune/inmunología , Animales , Candida albicans/crecimiento & desarrollo , Candidiasis/microbiología , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/inmunología , Perros , Resultado Fatal , Masculino , Pericardiocentesis/veterinaria , Pericarditis/microbiologíaRESUMEN
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.
Asunto(s)
Implantación de Prótesis Vascular/veterinaria , Prótesis Vascular/veterinaria , Enfermedades de los Perros/cirugía , Arteria Pulmonar/cirugía , Estenosis de la Válvula Pulmonar/veterinaria , Animales , Implantación de Prótesis Vascular/métodos , Enfermedades de los Perros/patología , Perros , Femenino , Fibrosis/patología , Histocitoquímica/veterinaria , Masculino , Microscopía Electrónica de Rastreo/veterinaria , Miocardio/patología , Arteria Pulmonar/patología , Arteria Pulmonar/ultraestructura , Estenosis de la Válvula Pulmonar/patología , Estenosis de la Válvula Pulmonar/cirugíaRESUMEN
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.
Asunto(s)
Implantación de Prótesis Vascular/veterinaria , Prótesis Vascular/veterinaria , Enfermedades de los Perros/cirugía , Estenosis de la Válvula Pulmonar/veterinaria , Animales , Presión Sanguínea/fisiología , Implantación de Prótesis Vascular/métodos , Angiografía Coronaria/veterinaria , Enfermedades de los Perros/patología , Perros , Ecocardiografía/veterinaria , Femenino , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/cirugía , Masculino , Arteria Pulmonar/patología , Arteria Pulmonar/cirugía , Estenosis de la Válvula Pulmonar/patología , Estenosis de la Válvula Pulmonar/cirugíaRESUMEN
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.
Asunto(s)
Bioprótesis/veterinaria , Perros/cirugía , Válvula Mitral/cirugía , Análisis de Varianza , Animales , Presión Sanguínea , Ecocardiografía , Electrocardiografía , Compuestos Epoxi , GlutaralRESUMEN
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.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Insuficiencia Cardíaca/prevención & control , Ventrículos Cardíacos/efectos de los fármacos , Animales , Ecocardiografía Transesofágica , Puente Cardíaco Derecho , Insuficiencia Cardíaca/cirugía , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Metoprolol/uso terapéutico , Células Musculares/efectos de los fármacos , Células Musculares/fisiología , Ratas , Disfunción Ventricular Izquierda/prevención & control , Disfunción Ventricular Izquierda/cirugía , Función Ventricular Izquierda/efectos de los fármacos , Función Ventricular Izquierda/fisiologíaRESUMEN
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.
Asunto(s)
Bioprótesis/veterinaria , Enfermedades de los Perros/cirugía , Prótesis Valvulares Cardíacas/veterinaria , Válvula Mitral/cirugía , Porcinos , Animales , Puente Cardiopulmonar/veterinaria , Perros , Masculino , Factores de TiempoRESUMEN
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.
Asunto(s)
Enfermedades de los Perros/cirugía , Estenosis de la Válvula Pulmonar/cirugía , Estenosis de la Válvula Pulmonar/veterinaria , Animales , Cateterismo/veterinaria , Enfermedades de los Perros/patología , Perros , Masculino , Estenosis de la Válvula Pulmonar/patologíaRESUMEN
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.
Asunto(s)
Enfermedades de los Perros/cirugía , Conducto Arterioso Permeable/veterinaria , Embolización Terapéutica/veterinaria , Animales , Perros , Conducto Arterioso Permeable/cirugía , Embolización Terapéutica/instrumentación , Embolización Terapéutica/métodos , Femenino , Masculino , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Cardiomiopatías/tratamiento farmacológico , Epoprostenol/análogos & derivados , Fibrosis/tratamiento farmacológico , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacología , Animales , Esquema de Medicación , Endocardio/patología , Epoprostenol/administración & dosificación , Epoprostenol/farmacología , Insuficiencia Cardíaca/prevención & control , Pruebas de Función Cardíaca , Ventrículos Cardíacos/patología , Longevidad , Ratas , Ratas Endogámicas DahlRESUMEN
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.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bencimidazoles/farmacología , Compuestos de Bifenilo/farmacología , Cardiomiopatía Dilatada/tratamiento farmacológico , Cardiomiopatía Dilatada/veterinaria , Fibrosis Endomiocárdica/tratamiento farmacológico , Fibrosis Endomiocárdica/veterinaria , Peptidil-Dipeptidasa A/metabolismo , Serina Endopeptidasas/metabolismo , Tetrazoles/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Animales , Bencimidazoles/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Peso Corporal/efectos de los fármacos , Cardiomiopatía Dilatada/enzimología , Cardiomiopatía Dilatada/patología , Quimasas , Cricetinae , Ecocardiografía , Fibrosis Endomiocárdica/enzimología , Fibrosis Endomiocárdica/patología , Ventrículos Cardíacos/patología , Histocitoquímica , Masculino , Miocardio/enzimología , Tamaño de los Órganos/efectos de los fármacos , Distribución Aleatoria , Tetrazoles/uso terapéuticoRESUMEN
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.
Asunto(s)
Insuficiencia Cardíaca/veterinaria , Peptidil-Dipeptidasa A/metabolismo , Serina Endopeptidasas/metabolismo , Remodelación Ventricular/fisiología , Angiotensina II/biosíntesis , Animales , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/veterinaria , Peso Corporal/fisiología , Quimasas , Cricetinae , Modelos Animales de Enfermedad , Enfermedades de los Perros/enzimología , Enfermedades de los Perros/patología , Perros , Ecocardiografía , Insuficiencia Cardíaca/enzimología , Insuficiencia Cardíaca/patología , Ventrículos Cardíacos/patología , Histocitoquímica , Masculino , Mesocricetus , Miocardio/enzimología , Tamaño de los ÓrganosRESUMEN
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.
Asunto(s)
Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Dinitrato de Isosorbide/administración & dosificación , Donantes de Óxido Nítrico/administración & dosificación , Administración Oral , Animales , Aorta Abdominal/cirugía , Peso Corporal , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Fibrosis Endomiocárdica/patología , Histocitoquímica , Hipertrofia Ventricular Izquierda/patología , Masculino , Miocitos Cardíacos/citología , Tamaño de los Órganos , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Fístula Arteriovenosa/tratamiento farmacológico , Resistencia a Medicamentos/fisiología , Dinitrato de Isosorbide/uso terapéutico , Vasodilatadores/uso terapéutico , Análisis de Varianza , Animales , Fístula Arteriovenosa/complicaciones , Presión Sanguínea , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Cardiomiopatía Hipertrófica/etiología , Preparaciones de Acción Retardada/uso terapéutico , Ecocardiografía , Dinitrato de Isosorbide/administración & dosificación , Masculino , Ratas , Ratas Wistar , Telemetría , Vasodilatadores/administración & dosificaciónRESUMEN
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.
Asunto(s)
Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía , Enfermedades de la Próstata/veterinaria , Ultrasonografía/veterinaria , Animales , Enfermedades de los Perros/patología , Perros , Masculino , Necrosis , Enfermedades de la Próstata/diagnóstico por imagen , Enfermedades de la Próstata/patología , Enfermedades de la Próstata/cirugía , Factores de Tiempo , Ultrasonografía/instrumentaciónRESUMEN
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.