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

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.

Effects of transforming growth factor-ß3 and matrix metalloproteinase-3 on the pathogenesis of chronic mitral valvular disease in dogs.

OBJECTIVE: To investigate the roles of transforming growth factor-ß (TGF-ß) isoforms and matrix metalloproteinases (MMPs) in development of chronic mitral valvular disease (CMVD) in dogs. SAMPLE POPULATION: 12 mitral valve leaflets collected from cadavers of 5 clinically normal dogs and from 7 dogs with CMVD. PROCEDURES: Expression of TGF-ß isoforms 1, 2, and 3; MMPs 1, 2, 3, and 9; TGF-ß receptor II (TßR-II); and α smooth muscle actin (αSMA) in mitral valves of dogs with CMVD was compared with that in mitral valves from clinically normal dogs. Additionally, responses of valvular interstitial cells (VICs) to TGF-ß3, MMP-3, and angiotensin-converting enzyme inhibitor (ACEI) as a suppressor of TGF-ß3 were examined in vitro. RESULTS: Expression of TGF-ß3, TßR-II, αSMA, and MMP-3 was only detected in mitral valves of dogs with CMVD. Concentrations of αSMA and proteoglycans in cultured VICs were significantly increased following incubation with TGF-ß3; treatment with MMP-3 resulted in increased amounts of active and total TGF-ß3, and total TGF-ß3 in VICs was significantly decreased by incubation with ACEI. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that increased TGF-ß3 and MMP-3 contribute to the pathogenesis of valvular degeneration associated with CMVD. In addition, it is possible that the use of ACEI could effectively block pathological alterations in VICs associated with CMVD in vitro. Impact on Human Medicine-CMVD is associated with primary mitral valve prolapse and Marfan syndrome in humans. Results of the study reported here will help to elucidate the molecular mechanisms of CMVD in dogs and humans.

Local intra-arterial administration of urokinase in the treatment of a feline distal aortic thromboembolism.

A 5-year old neutered male cat was admitted to our hospital in the early morning with sudden onset of bilateral hindlimbs paralysis. Conservative anticoagulant therapy using heparin, warfarin, and dipyridamole, and thrombolytic therapy with urokinase administered by intravenous infusion were started. However, no improvement was noted even after 2 days of treatment, and the cat was started on local intra-arterial administration of urokinase via a catheter on disease day 3. Successful thrombolysis could be accomplished by this approach, and the motor function of both hindlimbs recovered on disease day 5. The cat could be discharged on disease day 9. Complications such as hemorrhage and hyperkalemia were not observed during the thrombolytic therapy. These results suggest that local intra-arterial administration of urokinase may be an effective approach for the treatment of FATE.

Assessments of factors that affect glomerular filtration rate and indirect markers of renal function in dogs and cats.

Chronic kidney disease is one of the most common disorders in dogs and cats. The plasma urea nitrogen (P-UN) and creatinine (P-Cre) concentrations are not sufficiently sensitive for early diagnosis of renal dysfunction. Although urine and plasma clearance methods allow earlier detection of reductions in the GFR, it is difficult to estimate a mildly reduced GFR from the values obtained by these methods, as they are also affected by physiological factors, such as body weight (BW) and age. The present study is a retrospective survey designed to assess the factors that affect markers of kidney function and to revaluate the clinical utility of the markers, including P-UN, P-Cre and GFR determined by plasma iohexol clearance (PCio) in dogs and cats. The P-UN, P-Cre and PCio values in dogs and the P-Cre and PCio values in cats were significantly correlated with BW (P<0.001). PCio in smaller dogs (≤ 15.0 kg) was significantly and inversely correlated with age. In smaller dogs, increase of P-UN alone might warrant a suspicion of a decreased GFR, but in contrast, P-Cre may be inefficient for detecting renal dysfunction or determining the severity of CKD compared with that in larger dogs (≥ 15.1 kg). P-Cre in larger dogs correlated better with PCio than in smaller dogs, suggesting that P-Cre in larger dogs was a more sensitive marker of reduced GFR.

Application of gel permeation HPLC for lipoprotein profiling in dogs.

A high performance liquid chromatography system with a gel permeation column (GP-HPLC) and an on-line dual enzymatic system was applied to lipoprotein analysis in dogs. A high density lipoprotein (HDL) fraction obtained by conventional ultracentrifugation gave a single peak at around 28-29 min. Similarly, a low density lipoprotein (LDL) fraction gave single peak at around 24-25 min. The lipoprotein profiles of healthy dogs were contained large HDL peaks and small LDL peaks, and VLDL and CM were only marginally detected. In diabetic dogs, concentrations of VLDL-triglyceride and VLDL-total-cholesterol were elevated significantly. The lipoprotein profile analysis by GP-HPLC method would be useful in explication of abnormality of lipid metabolism in dogs.

Effects of enfonidipine hydrochloride in dogs with experimental supraventricular tachyarrhythmia.

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.

Evaluation of a single sampling method for estimation of plasma iohexol clearance in dogs and cats with various kidney functions.

Plasma iohexol clearance (PCio) is a practical method for measuring the glomerular filtration rate (GFR) in clinical settings. However, it is too time-consuming for routine application and requires hospitalization for at least half a day. Therefore, the development of a simpler procedure for plasma clearance is necessary to allow the frequent measurement of GFR in clinical settings. The purpose of the present study was to evaluate a single sampling method for estimation of PCio in dogs and cats with various kidney functions. The PCio determined by the 1-compartment model using 3 samples (PCio (3samples)) was used as a reference for the evaluation of the single sampling method (PCio (single)). Plasma iohexol concentration was determined by a cerium arsenite colorimetric method. PCio single was calculated using the equation obtained by nonlinear regression analysis. PCio (single) was significantly correlated with PCio (3samples) in both dogs and cats (dogs: R(2)=0.985, P<0.001, cats: R(2)=0.986, P<0.001). In a receiver operating characteristics analysis, the area under the curve, sensitivity, and specificity for detecting decreased GFR were 0.995 [SE, 0.003], 98%, and 93% for dogs and 0.993 [SE, 0.003], 98%, and 93% for cats, respectively. These results demonstrate that PCio (single) may be very useful for the detection of decreasing GFR in dogs and cats.

Effect of diet on the cardiovascular system in healthy beagles.

In management of canine cardiac disorders, cardiac drugs are commonly administered with food, although the cardiovascular effects of feeding and frequency of feeding are unknown. This study investigated the cardiovascular effect of feeding and frequency of feeding using a telemetry monitoring system in unanesthetized and unrestrained dogs. Systolic and diastolic blood pressure, heart rate and double product were steeply elevated during the five minutes immediately before feeding. They showed a sharp fall within 60 min after feeding time, especially the systolic and diastolic blood pressure, which showed lower values than from before feeding time. There were no significant differences in the means of preprandial elevation, postprandial fall or 24-hr averages in the once- and twice-daily feeding periods.

Evaluation of the measurement of serum cystatin C by an enzyme-linked immunosorbent assay for humans as a marker of the glomerular filtration rate in dogs.

The serum cystatin C (Cys-C) concentration is a better filtration marker than plasma creatinine (Cre) concentration in humans. In veterinary medicine, a few studies have shown that the serum Cys-C concentration in dogs is also a better marker than the plasma Cre concentration. The purpose of this study is to evaluate the applicability of measuring the serum Cys-C concentration by an enzyme-linked immunosorbent assay (ELISA) as a marker of the glomerular filtration rate in dogs with various renal dysfunctions. The serum Cys-C concentration in dogs with chronic kidney disease (CKD) was significantly higher (1.23 +/- 0.21 mg/L) than that in 76 control dogs (0.85 +/- 0.15) (P<0.001). The reference range of the serum Cys-C concentrations in samples from the 76 control dogs was 0.55-1.15 mg/l. Serum Cys-C concentration was more strongly correlated with plasma iohexol clearance (r=-0.704, P<0.001) than plasma Cre concentration in dogs (r=-0.598, P<0.001). In a receiver operating characteristics analysis, significant differences between the serum Cys-C and plasma Cre concentrations were found with regard to their AUC (0.949, [SE, 0.019] and 0.849 [SE, 0.029]) and diagnostic sensitivity (90.3% and 73.6%) for detecting decreased PCio (P<0.05). Therefore, the measurement of serum Cys-C concentration by ELISA is more useful for the detection of early CKD than measuring the plasma Cre concentration.

Evaluation of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in dogs with mitral valve insufficiency.

The diagnostic significance of the plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was evaluated in 72 dogs with mitral valve insufficiency and 36 control dogs. In the controls, the plasma NT-proBNP concentration was 163.9 +/- 114.7 (SD) pmol/l. The values in those with International Small Animal Cardiac Health Council (ISACHC) functional classification of heart failure class Ia, Ib, II and IIIa mitral valve insufficiency were 302.8 +/- 257.1 (n=21), 634.2 +/- 642.5 (n=23), 1,277.9 +/- 756.2 (n=18) and 1,908.9 +/- 538.8 (n=10) pmol/l, respectively; those in the class Ib or severer groups were significantly higher than that in the controls. In dogs in which the intensity of cardiac murmurs was Levine 3, 4, 5 and 6, plasma NT-proBNP concentrations were 647.6 +/- 577.3 (n=27), 1,184.7 +/- 841.0 (n=18), 1,532.4 +/- 784.2 (n=10) and 1,461.8 +/- 932.2 (n=4) pmol/l, respectively, and were significantly higher than that in the controls. The plasma NT-proBNP concentration was significantly correlated with the cardiac size (VHS) and LA/Ao (r=0.611, n=89, p<0.01; and r=0.705, n=91, p<0.01, respectively). When dogs with ISACHC class II or IIIa were regarded as heart failure, the cut-off value was 713.5 pmol/l, and the sensitivity and specificity were 0.913 and 0.857, respectively. These findings could indicate that plasma NT-proBNP concentration was significantly associated with the severity of heart failure due to mitral valve insufficiency in dogs. Further investigation is required to determine factors other than heart failure affecting plasma NT-proBNP concentration.

A bolus infusion of xylitol solution in the treatment of cow ketosis does not cause a surge in insulin secretion.

When a solution of xylitol was rapidly administered intravenously (bolus infusion) to healthy cattle or those with ketosis, different results were obtained. In healthy cattle, a temporary surge in insulin secretion was observed, whereas in ketotic cattle no such surge was found, but instead a moderate level of secretion continued for a lengthy period. No significant difference in the areas under the insulin curve (AUC) was found between healthy cattle and ketotic cattle up to 120 min after xylitol infusion. These results clearly demonstrated that a bolus infusion of xylitol solution in ketotic cattle does not cause a temporary surge in insulin secretion unlike in healthy animals, but rather results in a continuous, gradual rise in secretion.

Changes in peripheral lymphocyte subsets in the type 1 diabetic dogs treated with insulin injections.

Plasma metabolites and peripheral lymphocyte subsets were measured in ten diabetic and ten control dogs to investigate their significances as indicators to evaluate immune states in the diabetic dogs. Diabetic dogs were treated with insulin injections, however their plasma glucose and fructosamine concentrations were significantly higher than those of the controls. There were no significant differences in counts of total white blood cells (WBC) and lymphocyte CD8(+) cells (cytotoxic T cells) between the control and the diabetic dogs. In the diabetic dogs, the counts of CD3(+) (T cells), CD4(+) (Helper T cells) and CD21(+) (B cells) cells and the peripheral lymphocytes CD4/CD8 ratio were significantly lower than those in the control dogs. We confirmed abnormality of lymphocyte subsets in insulin treated diabetic dogs and it may relate to depression of immunocompetence and high susceptibility to common infectious diseases.

Influence of preemptive analgesia with meloxicam before resection of the unilateral mammary gland on postoperative cardiovascular parameters in dogs.

Preemptive analgesia is recommended in small animal medicine. However, many studies have evaluated the response to analgesic treatment by behavioral observation. Therefore, the influence of preemptive analgesia with meloxicam on postoperative cardiovascular and renal parameters remains to be clarified. The present study examined the changes in blood pressure, heart rate, double product and heart rate variability for 14 days and the changes in glomerular filtration rate (GFR) and serum cortisol level for 24 hr after resection of the unilateral mammary gland in meloxicam and control groups consisting of 5 healthy dogs. All data were collected under unanesthetized and unrestrained conditions using a radio telemetry system. Blood pressure, heart rate and double product were significantly lower in the meloxicam compared with the control group, and the meloxicam group's diurnal changes became stable more than 36 hr earlier than those of the control group. The systolic, diastolic and mean blood pressure values of the meloxicam group were 5- to 20-mm Hg lower than those of the control group until 5 days after surgery. The maximum difference between the two groups in terms of the double product values 14 days after surgery was 2,000 bpm x mmHg. Autonomic activity inhibition was prolonged in the control group. There were no significant differences in the 24-hr changes in GFR or serum cortisol level. This study showed that perioperative administration of meloxicam reduced unfavorable postoperative changes in the cardiovascular system without influencing renal function.

Evaluation of QT interval prolongation in dogs with heart failure.

Comparison of the QT interval and corrected QT interval values that were calculated by the methods of Bazett (QTc1) and Fridericia (QTc2) were made between dogs with or without cardiac diseases to determine the influence of the QT interval on canine heart failure. Upon comparison of the measured values on ECG between the cardiac disease and non-cardiac disease groups, it was observed that the heart rate(HR) was significantly higher in the cardiac disease group than in the non-cardiac disease group, although the QT interval was similar in the two groups. The QTc1 and QTc2 were significantly longer in the cardiac disease group than in the non-cardiac disease group. With the progression of the New York Heart Association Class, the HR tended to increase. The QTc1 and QTc2 became significantly prolonged with the progression of heart failure. Nevertheless, because Bazett's correction formula is known to overcorrect when the HR is high, it was considered that the QTc1 was actually overcorrected by high HR with the progression of heart failure. The QTc2, on the other hand, was only slightly influenced by HR, suggesting that the prolongation was due to the progression of heart failure. These results suggest that the prolongation of QTc2 in cardiac disease reflects the substantial prolongation of the QT interval without the influence of HR. It is suggested that the QTc2 could be a useful parameter for assessing the degree of heart failure in dogs with cardiac disease.

A case of canine gastrinoma.

The dog of this case was a 10-year-old Shih Tzu with refractory vomiting, diarrhea and anorexia. Endoscopy revealed an unclear at gastric angle, a stenosis at pyloric antrum and congestion in duodenal mucosa. Since abnormal shadows of irregular echo-levels were disclosed by pancreas ultrasonography, serum gastrin level was determined with a suspect of gastrinoma. And an increase of serum gastrin was demonstrated. In addition, postmortem histological examination revealed that the pancreatic cells were positive for gastrin. Based on these findings, the dog was diagnosed as pancreatic gastrinoma.

Acquired mitral stenosis in a cat with hypertrophic cardiomyopathy.

A seven-year-old castrated male domestic shorthair cat was diagnosed with hypertrophic cardiomyopathy (HCM) and suspected mitral stenosis (MS) based on electrocardiography, thoracic radiographs and echocardiographic findings. Post-mortem examination of the heart revealed morphological features consistent with HCM. In addition, there was marked fibrous deposition on the surfaces of the chordae tendineae extending to both mitral valve leaflets, which caused total chordal fusion into pillars of fibrous tissue and fusion of the commissures. The present case indicates that acquired MS can occur in association with HCM in the cat.

Ebstein's anomaly in a beagle dog.

An intact male beagle dog aged 1 year was referred because of shortness of breath, exercise intolerance and cardiac murmur. Based on the results from electrocardiography, thoracic radiography and echocardiography, the dog was diagnosed as Ebstein's anomaly. Although the orally administered digoxin, vasodilators and diuretics partially improved congestive signs, the dog became to be refractory and died 20 months after the diagnosis. Necropsy confirmed malformation and apical displacement of the basal attachment of tricuspid valve leaflets.

Lone atrial fibrillation in a dog.

An intact male Pointer aged 9 year was found to have atrial fibrillation (AF). Thoracic radiography and echocardiography as well as routine blood work revealed no cardiac disease. Thus, the dog was diagnosed as lone AF. The arrhythmia disappeared 6 hr after the initiation of the supportive therapy, and relapse was not observed.

Hypertrophic cardiomyopathy in a mixed breed cat family.

A spayed female mixed cat (case 1) and its female offspring, the result of a pairing between case 1 and its male sibling, were diagnosed with hypertrophic cardiomyopathy (HCM). A pedigree survey revealed that the prevalence of HCM was at least 12.5% in the family, which was considered to be significantly higher than that in a hospital-based population (approximately 1.6%). Thus, this finding seems to support the suspected occurrence of familial HCM in this group of related cats.