Acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs     

Sawangkoon S  Miyamoto M  Nakayama T  Hamlin RL 《American journal of veterinary research》2000,61(1):57-60

OBJECTIVE: To determine acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs. ANIMALS: 14 mature healthy Beagles. PROCEDURE: 12 dogs were anesthetized with morphine and alpha-chloralose. Catheters were placed in the aorta, left ventricle, and right atrium to record systemic and pulmonary pressures and determine vascular resistance and cardiac output. Electrocardiograms (leads I, aVF, and V3) were recorded to determine electrocardiographic changes. Variables were measured before and after IV injection of incremental doses of carvedilol (cumulative doses, 10, 30, 70, 150, 310, and 630 microg/kg of body weight; n = 6) or vehicle alone (6). Pharmacokinetic analysis was performed, using 2 conscious dogs given 160 microg of carvedilol/kg as a single IV injection. RESULTS: Heart rate and velocity of fiber shortening at zero load (Vmax) increased slightly but significantly from baseline values at doses of carvedilol > or = 310 microg/kg and 10 microg/kg, respectively. Carvedilol did not affect systemic and pulmonary pressures or vascular resistances. Intravenous administration of approximately 150 microg of carvedilol/kg resulted in a plasma carvedilol concentration of approximately 100 ng/ml. Mean elimination half-life was 54 minutes, half-life of distribution was 3.5 minutes, and volume of distribution was 2,038 ml/kg. CONCLUSIONS AND CLINICAL RELEVANCE: The therapeutic plasma concentration of carvedilol in humans is 100 ng/ml. At that plasma concentration in dogs, the reduction in afterload and positive inotropic effect that we observed would be beneficial for treating heart failure and minimizing the cardiotoxic effects of doxorubicin.  相似文献   

Hemodynamic and electrophysiologic effects of ontazolast in dogs     

Hamlin RL  Nakayama T  Brady JT  Stoll RE 《American journal of veterinary research》2000,61(11):1364-1368

OBJECTIVE: To determine whether QT interval is prolonged or sudden death is caused by ventricular fibrillation resulting from torsades de pointes and to identify hemodynamic effects of ontazolast. ANIMALS: 28 Beagles. PROCEDURE: Physiologic variables were measured for 2 hours in conscious dogs given ontazolast (0, 1, or 3 mg/kg of body weight, IV) and for 1 hour in anesthetized dogs given cumulative doses of ontazolast (0, 1, 3, 6, or 8 mg/kg, IV). RESULTS: Ontazolast prolonged QT interval and QT interval corrected for heart rate (QTc) at doses of 6 mg/kg in anesthetized dogs. At 8 mg/kg, both variables remained prolonged but tended to decrease. In conscious dogs, ontazolast increased QT interval and QTc 15 minutes after administration, but both variables returned to reference ranges by 60 minutes. In conscious dogs, ontazolast increased maximum rate of increase of left ventricular pressure and maximal velocity of fiber shortening, indicators of inotropy, and increased tau, indicating a decreased rate of relaxation. One conscious dog receiving 3 mg/kg developed nonfatal torsades de pointes, but another conscious dog developed ventricular fibrillation. Two anesthetized dogs receiving 6 mg/kg developed early afterdepolarizations, and all dogs developed secondary components in theirT waves. CONCLUSION AND CLINICAL RELEVANCE: Ontazolast possesses potent class-III antiarrhythmic properties and induces prolongation of QTc in a dose-dependent fashion. Because there was a clear dose-dependent prolongation of QT interval in all instances, ontazolast may serve as a positive-control compound for studying other compounds that are believed to prolong the QT interval.  相似文献   

Prolymphocytic T-cell lymphosarcoma in a dog     

J Sugimoto  H Nakayama  R Takahashi  K Fujiwara 《Nippon juigaku zasshi. The Japanese journal of veterinary science》1987,49(5):901-902

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Teratogenic action of hypoxia under normal atmospheric pressure     

Y Noguchi  Y Nakayama  Y Kowa 《Nippon juigaku zasshi. The Japanese journal of veterinary science》1967,29(1):11-19

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Gel diffusion test in feline infectious peritonitis with infected suckling mouse brain antigen     

H Nakayama  T Hayashi  Y Watabe  T Yanagisawa  K Fujiwara 《Nippon juigaku zasshi. The Japanese journal of veterinary science》1982,44(4):695-697

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Acute cardiovascular effects of diltiazem in anesthetized dogs with induced atrial fibrillation     

Miyamoto M  Nishijima Y  Nakayama T  Hamlin RL 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2001,15(6):559-563

Atrial fibrillation (AF) is one of the most important arrhythmias of dogs. In a previous study, we determined the dosage of intravenously administered diltiazem necessary to reduce ventricular response (VR), cardiac output (CO), and mean systemic arterial pressure (P(Ao)) to values similar to those observed during sinus rhythm (SR) before induction of AF. The present study was conducted to establish an acute, effective dosage of diltiazem given PO. AF was produced by rapid atrial pacing in healthy, anesthetized Beagle Hounds. Dogs were instrumented to record hemodynamic and electrophysiological parameters. Four dogs were given 2.5 mg/kg diltiazem, and another 4 dogs were given 5 mg/kg diltiazem by stomach tube, whereas 4 other dogs received vehicle in equivalent volumes. Plasma concentrations of diltiazem were measured at various intervals after dosing. A dosage of 5 mg/kg diltiazem produced plasma concentrations of 32-100 ng/mL 3 hours after administration, concentrations within the published effective range for dogs with naturally occurring AF. Between 2 and 3 hours after this dosage, the rate pressure product (RPP) and an index of left ventricular efficiency returned to values similar to those observed during SR. Thus, we believe that diltiazem at anorally administered dosages of 5 mg/kg should be considered to produce therapeutic blood concentrations and favorable hemodynamic effects in dogs with naturally occurring AF. These data must be extrapolated with caution to dogs with long-standing AF produced by natural causes.  相似文献   

Congenital cystic adenomatoid-like malformation in a cynomolgus monkey (Macaca fascicularis)     

Okabayashi S  Ohno C  Kato M  Nakayama H  Yasutomi Y 《Veterinary pathology》2008,45(2):232-235

Congenital cystic adenomatoid malformation (CCAM) is a developmental lung abnormality characterized by abnormal proliferation of mesenchymal elements and failure of bronchiolar structures to mature, ultimately resulting in the compression of normal pulmonary tissue and mediastinal shift with rapid expansion of cysts. Although various clinical and pathologic studies of CCAM in humans exist, CCAM has yet to be reported in animals, even in nonhuman primates. In the present study, histopathologic analyses of a neonatal cynomolgus monkey that died 17 days after birth revealed that normal lung architecture was replaced by disorganized overgrowths of cysts lined with simple cuboidal epithelium. The epithelium projected a few ciliates into the air spaces and produced mucus. To our knowledge, this is the first case study describing CCAM or a CCAM-like lesion in nonhuman primates.  相似文献   

Association of tumour‐infiltrating regulatory T cells with adverse outcomes in dogs with malignant tumours          下载免费PDF全文

K. Sakai  S. Maeda  Y. Yamada  J. K. Chambers  K. Uchida  H. Nakayama  T. Yonezawa  N. Matsuki 《Veterinary and comparative oncology》2018,16(3):330-336

Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and associate with poor prognosis in humans. However, data on association of Treg infiltration with prognosis is limited in canine tumours. The purpose of this study was to examine the number of tumour‐infiltrating Tregs and its association with overall survival (OS) in dogs with malignant tumours. The following 168 canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number of forkhead box P3 (Foxp3)‐positive Tregs in intratumoral and peritumoral areas was investigated by immunohistochemistry. OS was compared between high and low Treg groups. The number of intratumoral and peritumoral Foxp3‐positive Tregs was significantly higher in OMM, OSCC, PA and MC compared with each normal tissue. There were few Foxp3‐positive Tregs in MCT and HCC. With intratumoral Tregs, the OS in the high Treg group was significantly shorter than that in the low Treg group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant difference for OS between the 2 groups in each tumour type. These results suggest that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs are associated with poor prognosis in some solid tumour types.  相似文献   

Aspiration pneumonia as a cause of neonatal death in three captive bottlenose dolphins (Tursiops truncates)     

Makara M  Shimada A  Kawamura N  Murase T  Morita T 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2007,69(3):325-327

Neonatal weakness of calves is one of the common reproductive-related problems in captive cetaceans; clinical signs can be observed in the first few hours after delivery. Three 3-day-old bottlenose dolphins died with history of weakness since birth. Pathological study demonstrated purulent bronchopneumonia associated with prominent bacterial colonies and foreign substances in alveoli, suggesting aspiration pneumonia as a cause of neonatal weakness and resultant death of the three calves.  相似文献   

TRIPLE‐PHASE HELICAL COMPUTED TOMOGRAPHY IN DOGS WITH HEPATIC MASSES     

Kenji Kutara  Mamiko Seki  Chieko Ishikawa  Manabu Sakai  Yumiko Kagawa  Gentoku Iida  Kumiko Ishigaki  Kenji Teshima  Kazuya Edamura  Tomohiro Nakayama  Kazushi Asano 《Veterinary radiology & ultrasound》2014,55(1):7-15

The purpose of this study was to determine the utility of triple‐phase helical computed tomography (CT) for differentiating canine hepatic masses. Seventy dogs with hepatic masses underwent triple‐phase CT followed by surgical removal of the hepatic masses. Triple‐phase helical CT scans for each dog included precontrast, arterial phase, portal venous phase, and delayed phase studies. The removed hepatic masses were histopathologically classified as hepatocellular carcinoma (n = 47), nodular hyperplasia (n = 14), and hepatic metastatic tumors (n = 9) in dogs. Of the 47 hepatocellular carcinomas, the most common CT findings included a heterogeneous pattern with hyper‐, iso‐, and hypoenhancement in both the arterial and portal venous phases (40/47, 85.1%). Of the 14 nodular hyperplasias, the most common CT findings were a homogeneous pattern with hyper‐ and isoenhancement in both the portal venous and delayed phases (13/14, 92.9%). Of nine hepatic metastatic tumors, the most common CT findings included a homogeneous hypoenhancement pattern in both the arterial and portal venous phases (8/9, 88.9%). In addition, 5 (55.6%) showed homogeneous hypoenhancement patterns in the delayed phase. Findings from our study indicated that triple‐phase CT is a useful tool for preoperative differentiation of hepatocellular carcinoma, nodular hyperplasia, and hepatic metastatic tumors in dogs.  相似文献