Cardiac Inflammatory Myofibroblastic Tumours in Three Young Adult Cats.

Inflammatory myofibroblastic tumours (IMTs) of the heart are described in three young adult cats (case 1, 3.5 years old; case 2, 2.7 years old; case 3, 1.8 years old) that died due to pleural and pericardial effusions resulting from congestive heart failure. At necropsy, cardiac masses, measuring 4 × 3 × 2.5 cm (case 1), 3.5 × 2.5 × 2 cm (case 2) and 3 × 2.5 × 2 cm (case 3), were located mainly in the right auricle (case 1) and atrial septum (cases 2 and 3) with variable extension into the surrounding tissue. Histologically, the atrial masses in all three cats comprised proliferation of spindloid mesenchymal cells and an inflammatory infiltrate of plasma cells and lymphocytes in variable amounts of myxoid background. The spindloid cells were uniform and characterized by pale eosinophilic cytoplasm and a vesicular nucleus containing prominent nucleoli, with no remarkable cytological atypia or mitotic activity. Immunohistochemically, these cells were positive for vimentin and α-smooth muscle actin in all cases, supporting a myofibroblastic origin. The histopathological and immunohistochemical features were consistent with those of IMTs in humans and animals. There have been no previous reports of such tumours occurring in the heart of the cat.

Comparison of N-terminal pro-atrial natriuretic peptide and three cardiac biomarkers for discriminatory ability of clinical stage in dogs with myxomatous mitral valve disease.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.

Epidemiological study of indirect blood pressure measured using oscillometry in clinically healthy cats at initial evaluation.

We investigated the clinical characteristics of healthy cats in accordance with the target organ damage (TOD) risk category, on the basis of systolic blood pressure (SBP). This prospective multi-center study included 137 healthy cats. Indirect blood pressure was measured using an oscillometric technique. The median SBP in all cats was 147 mmHg (interquartile range: 134-158). On the basis of the TOD risk category, 57.7, 19.7, 21.9, and 0.7% of the cats were classified into categories I-IV, respectively. Age, sex, and body weight did not affect the SBP. This study provides basic information on the distribution of TOD risk categories in clinically healthy cats.

Surgery for partial atrioventricular septal defect with pulmonary hypertension in an adult dog.

A 4-year-old, 5.9-kg female Japanese Spitz presented with syncope and exercise intolerance. Echocardiography revealed an ostium primum atrial septal defect (ASD), a cleft mitral valve, mitral valve regurgitation (MR), and tricuspid regurgitation (TR) (velocity: 3.6 m/sec, pressure gradient: 52 mmHg), leading to a diagnosis of partial atrioventricular septal defect (AVSD) with moderate pulmonary hypertension (PH). Open-heart surgery using cardiopulmonary bypass was performed through right atriotomy. The cleft of the mitral valve was sutured with polypropylene and the AVSD was closed using an autologous pericardial patch fixed with glutaraldehyde. No postoperative pulmonary hypertensive crisis occurred. Shunting flow through the ASD, TR and PH had completely disappeared 2 months postoperatively; however, moderate MR persisted. The dog is still alive 5 years postoperatively without clinical signs.

Effects of the angiotensin-converting enzyme inhibitor alacepril in dogs with mitral valve disease.

Alacepril is a relatively novel angiotensin-converting enzyme inhibitor; however, the safety, tolerance, and efficacy of alacepril in terms of cough suppression in dogs with mitral valve disease (MVD) remain unknown. The aim of this study was to investigate the safety, tolerance, and cough suppression efficacy of alacepril in dogs with MVD. This was a multi-center, prospective study. Forty-two dogs with echocardiographic or radiographic evidence of cardiac enlargement in addition to cough were enrolled. Dogs were treated with alacepril (1.0-3.0 mg/kg/day) for at least 4 weeks. One dog (2.4%) developed complications, including appetite loss, lethargy, and vomiting. Thirty-six dogs were re-evaluated after 4 weeks of treatment. Cough resolved or improved in 20 dogs (55.6%) after treatment. Based on the efficacy of alacepril, the dogs were divided into an effective group (n=20) and an ineffective group (n=16). After treatment, the left ventricular end-diastolic internal diameter corrected for body weight was significantly increased from baseline in the ineffective group but was significantly decreased in the effective group. Univariate binomial logistic regression analyses showed that high atrial natriuretic peptide level, N-terminal pro-B-type natriuretic peptide level, and E wave velocity at baseline were significantly correlated with alacepril inefficacy. Alacepril as treatment for MVD is well tolerated in most dogs, and different conditions of cardiac loading may influence the effect of the drug. Alacepril is expected to improve the quality of life of dogs with early stage MVD.

Diagnostic utility of cardiac troponin I in cats with hypertrophic cardiomyopathy.

BACKGROUND: Cardiac troponin I (cTnI) is useful for assessing hypertrophic cardiomyopathy (HCM) in cats. OBJECTIVE: To measure plasma cTnI concentrations in healthy cats and evaluate the clinical utility of cTnI in determining the severity of HCM. ANIMALS: Clinically healthy cats (n = 88) and cats with HCM (n = 93). METHODS: Multicenter prospective study. Cats with HCM, including hypertrophic obstructive cardiomyopathy at various stages, were diagnosed using echocardiography. Plasma cTnI concentrations were analyzed by a commercial laboratory. Receiver-operating characteristic curve analysis was used to evaluate the accuracy of plasma cTnI concentrations to detect HCM. RESULTS: The median cTnI concentration was 0.027 ng/mL (interquartile range, 0.012-0.048 ng/mL) in healthy cats. Concentrations were significantly higher in diseased cats than in healthy controls, and concentrations were significantly higher in cats with heart failure than in asymptomatic cats. A plasma cTnI concentration of 0.163 ng/mL had a sensitivity of 62.0% and specificity of 100% when used to distinguish normal cats from asymptomatic HCM cats without left atrial dilatation. A cutoff of 0.234 ng/mL had high sensitivity (95.0%) and specificity (77.8%) for assessing heart failure. The areas under the receiver-operating characteristic curves were 0.85 and 0.93, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased cTnI concentrations reflect the severity of HCM. If other causes of cardiac injury are ruled out, plasma cTnI concentration may be useful for predicting the severity of HCM in cats.

Relationship between indirect blood pressure and various stages of chronic kidney disease in cats.

Chronic kidney disease (CKD) is a common cause of secondary systemic hypertension in cats. We investigated the relationship between indirect blood pressure and the prevalence of systemic hypertension in various CKD stages in cats. Client-owned cats (24 control cats and 77 cats with CKD) were included. Biochemical examinations of plasma were conducted by a commercial laboratory. Diseased cats were divided into two groups based on the International Renal Interest Society (IRIS) guidelines (II and III-IV). Indirect blood pressure was measured using an oscillometric technique. Severe hypertension was diagnosed if systolic blood pressure (SBP) was ≥180 mmHg. Indirect blood pressures were significantly higher in IRIS stage III-IV than in the control cats. Of 77 cats with CKD, 25 (32.5%) had severe hypertension. The frequency of severe hypertension increased with an increase in IRIS stage; 0% in the controls, 27.6% in the IRIS stage II, and 47.4% in the IRIS stage III-IV, respectively. The indirect SBP was weakly correlated with urea nitrogen (r=0.27) and creatinine (r=0.23) concentrations in plasma. Binary logistic regression analysis showed that if plasma creatinine concentration is >3.7 mg/dl, cats with CKD had an increased risk for developing severe hypertension (P<0.001). Our results suggest that indirect blood pressure was correlated with the severity of CKD, and the prevalence of severe hypertension increased in cats with severe CKD. The risk of severe hypertension may be high in cats with severe CKD.

Long term effects of cilostazol in a dog with sick sinus syndrome.

Sick sinus syndrome (SSS) is a type of bradyarrhythmia that can lead to syncope. Cilostazol has been reported to be an effective treatment for human patients with SSS and other bradyarrhythmias. This report describes the successful long-term treatment with cilostazol in a dog with SSS. A nine-year old intact male Miniature Schnauzer presented with a history of syncopal episodes and unsteady gait. After cilostazol treatment, the total heart rate (HR), mean HR, and frequency of premature ventricular contractions (PVCs) increased, while the maximum HR and maximum pause time decreased. Additionally, the number of syncopal episodes decreased. The dog died suddenly, 1,418 days after the start of cilostazol treatment. Cilostazol may be a useful therapeutic agent in canines with SSS.

Plasma atrial natriuretic peptide and N-terminal pro B-type natriuretic peptide concentrations in dogs with right-sided congestive heart failure.

The clinical utility of plasma natriuretic peptide concentrations in dogs with right-sided congestive heart failure (CHF) remains unclear. We investigated whether plasma levels of atrial natriuretic peptide (ANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are useful for assessing the congestive signs of right-sided heart failure in dogs. This retrospective study enrolled 16 healthy dogs and 51 untreated dogs with presence (n=28) or absence (n=23) of right-sided CHF. Medical records of physical examinations, thoracic radiography and echocardiography were reviewed. The plasma concentration of canine ANP was measured with a chemiluminescent enzyme immunoassay. Plasma NT-proBNP concentrations were determined using an enzyme immunoassay. Plasma ANP and NT-proBNP concentrations in dogs with right-sided CHF were significantly higher than in healthy controls and those without right-sided CHF. The plasma NT-proBNP concentration >3,003 pmol/l used to identify right-sided CHF had a sensitivity of 88.5% and specificity of 90.3%. An area under the ROC curve (AUC) was 0.93. The AUC for NT-proBNP was significantly higher than the AUCs for the cardiothoracic ratio, vertebral heart score, ratio of right ventricular end-diastolic internal diameter to body surface area, tricuspid late diastolic flow and ratio of the velocities of tricuspid early to late diastolic flow. These results suggest that plasma ANP and NT-proBNP concentrations increase markedly in dogs with right-sided CHF. Particularly, NT-proBNP is simple and helpful biomarkers to assess the right-sided CHF.

Plasma adrenomedullin concentration in dogs with myxomatous mitral valvular disease.

Adrenomedullin (AM), a peptide identified to have vasodilating and natriuretic effects, is involved in the regulation of the cardiovascular system. To evaluate plasma AM concentration in dogs with myxomatous mitral valvular disease (MMVD), and to investigate the associations between the concentrations of plasma AM and natriuretic peptides and the echocardiographic data, we evaluated plasma AM concentrations in 31 healthy control dogs and 57 dogs with MMVD. Plasma AM concentrations in dogs with MMVD were higher than that in the control subjects. The plasma AM concentration increased in conjunction with the severity of heart failure according to the International Small Animal Cardiac Health Council (ISACHC). The AM concentrations were 25.1 ± 5.0 fmol/ml (ISACHC class Ia), 29.9 ± 11.0 fmol/ml (ISACHC class Ib), 43.4 ± 19.8 fmol/ml (ISACHC class II) and 73.5 ± 21.7 fmol/ml (ISACHC class III) and 7.5 ± 5.1 fmol/ml (control group), respectively. The receiver operating characteristic curve indicated an area of 0.93 (95% CI, 0.8801-0.9889; <0.0001), a cutoff value of 30.5 fmol/ml, a sensitivity of 87.1%, and a specificity of 82.5% for the determination of congestive heart failure. Plasma AM concentrations correlated with atrial natriuretic peptide concentrations, LA/Ao ratio, and left ventricular diameter. In conclusion, AM may be a potential diagnostic marker for canine MMVD and possibly plays a pathophysiological role in collaboration with the other neurohumoral factors such as natriuretic peptides.

Cloning of prepro-adrenomedullin and mRNA expression in cats.

The objective of this paper was to evaluate the sequence of feline prepro-adrenomedullin (AM) and its tissue distribution and to investigate whether expression of feline AM mRNA increases in association with spontaneous cardiomyopathy. The feline prepro-AM cDNA sequence and deduced amino acids were 564 base pairs and 188 residues, respectively. The cDNA sequences of feline prepro-AM including AM and proadrenomedullin N-terminal 20 peptide showed high homology with those of other mammalian species. The mRNA expression of AM was detectable in various normal tissues. The mRNA levels of AM were elevated in hearts with cardiomyopathy compared with normal hearts. This study suggests that AM has an important role as a neurohumoral factor in cats with spontaneous heart diseases.

Hemodynamic and biochemical changes during total hepatic vascular exclusion in dogs.

Twelve healthy Beagles were divided into 3 groups of 4 dogs each. To compare 2 methods of total hepatic vascular exclusion (THVE), we investigated the hemodynamic changes during THVE and assessed the influences on hepatic, renal and pancreatic biochemistry and the complications after THVE. In Group A, the thoracic aorta, hepatic pedicle and prehepatic and posthepatic caudal vena cava were occluded for 20 min, while in Group B, the celiac and cranial mesenteric arteries, hepatic pedicle and prehepatic and posthepatic caudal vena cava were occluded for 20 min. In Group C, a sham operation was performed. The arterial, venous and portal venous pressures and serum biochemistry parameters were measured before and during THVE and for 30 min after reperfusion. The carotid arterial pressure did not change in Group A during THVE, but decreased in Group B. The femoral and portal venous pressures in Group B increased significantly during THVE compared with those in Group C. With the exception of alanine aminotransferase, the serum biochemical profiles remained unchanged after the operation. For 7 days after the operation, no complications were observed in any of the dogs. In conclusion, occlusion of thoracic aorta, hepatic pedicle and prehepatic and posthepatic caudal vena cava is a feasible and safe method of hepatic vascular occlusion. This technique appears to be effective for canine hepatic surgery, such as removal of a large right-divisional hepatic tumor and attenuation of intrahepatic portosystemic shunt.

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.

Gene expression of adrenomedullin in canine normal tissues and diseased hearts.

The purposes of this study were to determine the tissue distribution of canine adrenomedullin (AM) and to determine whether increased canine AM mRNA expression is associated with congestive heart failure (CHF) due to mitral regurgitation (MR). Canine AM mRNA expression was detectable in various normal tissues, including cardiovascular tissues. In addition, the AM mRNA expression in the left atrium of dogs with MR was significantly higher than that in normal subjects. In conclusion, AM is a potential neurohumoral factor in dogs with CHF due to MR.

Effects of pimobendan for mitral valve regurgitation in dogs.

Pimobendan has a dual mechanism of action: it increases myocardial contractility by increasing calcium sensitization to troponin C and it promotes vasodilation by inhibiting PDEIII. This study examined the effects of pimobendan on cardiac function, hemodynamics, and neurohormonal factors in dogs with mild mitral regurgitation (MR). The dogs were given 0.25 mg/kg of pimobendan orally every 12 hr for 4 weeks. With pimobendan, the heart rate and stroke volume did not change, but the systolic blood pressure gradually decreased and the degree of mitral valve regurgitation tended to decrease. Renal blood flow was significantly increased and the glomerular filtration rate was slightly increased at 2 and 4 weeks. Furthermore, over the 4-week period, the plasma norepinephrine concentration decreased significantly, the systolic index increased slightly, the left atrial diameter and the left ventricular diameters decreased significantly, and the heart size improved. Given these results, pimobendan appears to be useful for treating MR in dogs. However, further long-term studies of pimobendan involving a larger number of dogs with mild and moderate MR are needed to establish the safety of pimobendan and document improvements in quality of life.

Evaluation of left ventricular Tei index (index of myocardial performance) in healthy dogs and dogs with mitral regurgitation.

The left ventricular (LV) Tei index (index of myocardial performance) has been demonstrated to be clinically useful in estimating comprehensive LV function, including the systolic and diastolic performances, in various human cardiac diseases. The purposes of this study were to validate the correlation between the LV Tei index and LV function obtained by cardiac catheterization in healthy dogs, and to evaluate the LV Tei index in dogs with naturally occurring mitral regurgitation (MR). In healthy dogs, the LV Tei index was significantly correlated with the LV peak +dP/dt (r = -0.89) and LV peak -dP/dt (r=0.87). The LV Tei index significantly increased in dogs with MR compared with normal dogs and significantly increased with progressively more severe clinical signs due to heart failure. The elevation of the LV Tei index in dogs with symptomatic MR appears to be associated with shortening of ejection time. The LV Tei index significantly increased with age and was not correlated with heart rate and body weight in normal dogs. In conclusion, our study demonstrated that the LV Tei index was measurable in dogs and not influenced by heart rate and body weight. The LV Tei index significantly increased with the progression of clinical signs in MR dogs. In particular, the elevation of the LV Tei index in dogs with symptomatic MR due to shortening of ejection time may suggest LV systolic dysfunction and the decrement of forward stroke volume.

A survey of indoor workplace radon concentration in Japan.

Radon ((222)Rn) concentration was measured at indoor workplaces in Japan to estimate effective dose to the public from (222)Rn and its progeny. Measurements were made from 2000 to 2003 at 705 sites in four categories of office, factory, school and hospital. Passive type Rn monitors equipped with two sheets of polycarbonate thin films for measuring radon concentrations were installed at observation sites and replaced every 3 months to observe seasonal variations in (222)Rn concentrations. The range of annual mean (222)Rn concentrations for all sites was 1.4-182 Bq m(-3), with the arithmetic mean and standard deviation were 20.8 and 19.5 Bq m(-3). Annual mean (222)Rn concentration observed at office, factory, school and hospital were 22.6, 10.1, 28.4 and 19.8 Bq m(-3), respectively. Seasonal variations in (222)Rn concentrations at offices, schools and hospitals were similar to those found in dwellings, and variations in factories were similar to those found in outdoor environments. (222)Rn concentration observed in every quarter period was found to decrease as follows: school>office>hospital>factory. The average effective dose to the public due to (222)Rn was estimated to be 0.41 mSv y(-1) weighted by the working population. Considering the (222)Rn exposure in indoor workplaces, effective dose to the general public is estimated to be in the range from approximately 0.42 to 0.52 mSv y(-1).

A nationwide survey of outdoor radon concentration in Japan.

Nationwide outdoor radon (222Rn) concentrations in Japan were measured to survey the environmental outdoor 222Rn level and to estimate the effective dose to the general public from 222Rn and its progeny. The 222Rn concentration was measured with a passive-type radon monitor. The 222Rn monitors were installed at about 700 points throughout Japan from 1997 to 1999. The annual mean 222Rn concentration in Japan was estimated from four quarters measurements of 47 prefectures in Japan. Nationwide outdoor mean 222Rn concentration was 6.1 Bq m(-3). This was about 40% of the indoor 222Rn concentration in Japan. The 222Rn concentration in Japan ranged from 3.3 Bq m(-3) in the Okinawa region to 9.8 Bq m(-3) in the Chugoku region, reflecting geological characteristics. Seasonal variation of outdoor 222Rn concentration was also found to be lowest in July to September, and highest in October to December. From the results of this 222Rn survey and previous indoor 222Rn survey program, the effective dose to the general public from 222Rn and its progeny was estimated to be 0.45 mSv y(-1).