The Aldosterone Receptor Antagonist Eplerenone Inhibits Isoproterenol-Induced Collagen-I and 11ß-HSD1 Expression in Rat Cardiac Fibroblasts and the Left Ventricle.

ß-Adrenergic receptor (ß-AR)-induction of collagen-I synthesis is partially mediated by the cardiac mineralocorticoid receptor (MR) system. However, it remains unclear whether the selective MR antagonist, eplerenone, inhibits collagen-I synthesis induced by ß-AR stimulation. We investigated the effects of eplerenone on the responses to a non-selective ß-AR agonist, isoproterenol, which induced collagen-I synthesis in primary cardiac fibroblasts (CFs) and the left ventricle. mRNAs encoding the MR and 11ß-hydroxysteroid dehydrogenase type I (11ß-HSD1) were evident in the left ventricle and primary CFs. mRNAs encoding the CYP family 11 subfamily B member 2 (CYP11-B2) were not detected, even after isoproterenol treatment. In vivo, isoproterenol induced collagenous fiber accumulation in the left ventricle. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), 11ß-HSD1 levels, and mRNA/protein levels of collagen-I increased upon exposure to isoproterenol, but these increases were inhibited by eplerenone co-treatment. In primary CFs, isoproterenol increased the phosphorylation of ERK1/2 and the expression levels of both 11ß-HSD1 and collagen-I; these isoproterenol-attributable effects were inhibited by co-treatment with eplerenone and PD98059, a specific inhibitor of mitogen-activated protein kinase/ERK kinase activity. The results suggest that 11ß-HSD1 but not CYP11-B2 is expressed in primary CFs. Eplerenone inhibited isoproterenol-induced ERK1/2 phosphorylation and expression of 11ß-HSD1 and collagen-I in primary CFs, as well as the progression of cardiac fibrosis in the left ventricle. Therefore, eplerenone inhibited the isoproterenol-induced increases in 11ß-HSD1 and collagen-I expression in primary CFs, and progression of cardiac fibrosis in the left ventricle.

Prevalence of intestinal parasites in breeding kennel dogs in Japan.

The present study is the first to show overall prevalences of intestinal parasites among breeding kennel dogs in Japan. A total of 573 fresh fecal samples were collected from dogs at 12 breeding kennels. Giardia-specific coproantigen was examined by ELISA kit (SNAP(®) Giardia, IDEXX Laboratories, Inc., Maine, USA). Other intestinal parasites were determined microscopically using the formalin-ethyl acetate sedimentation technique. Overall prevalences of two genera of protists, Giardia spp. and Cystoisospora spp., were 25.7 and 1.2 %, respectively. The prevalence of helminthes was recorded as: Toxocara canis 0.2 %, Toxascaris leonina 0.9 %, Ancylostoma caninum 0.2 %, Trichuris vulpis 2.1 %, and Spirometra erinacei 0.4 %. According to age categories, Giardia spp., Cystoisospora spp., and T. leonina in <1-year-old dogs were significantly more prevalent than in ≥ 1-year-old dogs (61.0 vs. 19.8 %, P < 0.0001; 7.3 vs. 0.2 %, P < 0.0001; and 4.9 vs. 0.2 %, P < 0.001; respectively). With respect to fecal condition, the prevalences of T. leonina and T. vulpis were significantly higher in unformed stool dogs than in formed ones (2.4 vs. 0 %, P < 0.01, and 4.3 vs. 0.8 %, P < 0.05, respectively). In all of the breeding kennels except for one kennel, intestinal parasite infections were found at the high prevalent, ranging from 16.0 to 70.0 %.

Matrix metalloproteinase-2 stimulates collagen-I expression through phosphorylation of focal adhesion kinase in rat cardiac fibroblasts.

Collagen-I is thought to be the main component of the extracellular matrix in cardiac fibrosis, the accumulation of which occurs with excessive activation of matrix metalloproteinase-2 (MMP-2). MMP-2 degrades the extracellular matrix; however, the relative importance of MMP-2 to collagen-I synthesis in cardiac fibroblasts remains unclear. We investigated whether extracellular activation of MMP-2 regulates collagen-I synthesis and phosphorylation of focal adhesion kinase (FAK) in rat cardiac fibroblasts. Primary cultures of rat cardiac fibroblasts were incubated with purified active MMP-2 to determine whether extracellular MMP-2 affects collagen-I synthesis and FAK phosphorylation in cardiac fibroblasts. Exogenous MMP-2 significantly stimulated FAK (Tyr397) phosphorylation and induced collagen-I expression in a time-dependent manner. Simultaneous treatment with the FAK inhibitor PF573228 abolished exogenous MMP-2-enhanced FAK (Tyr397) phosphorylation and collagen-I expression. Cells were then stimulated with norepinephrine (NE) to investigate whether endogenous MMP-2 could also induce collagen-I expression through FAK (Tyr397) phosphorylation. NE-stimulated endogenous MMP-2 activation in conditioned medium was significantly attenuated by simultaneous treatment with the MMP inhibitor PD166793. Similarly, NE-induced FAK (Tyr397) phosphorylation and collagen-I expression were significantly inhibited by simultaneous treatment with PD166793 or PF573228. Furthermore, MMP-2 knockdown induced by small interfering RNA (siRNA) significantly abolished endogenous MMP-2 expression and activation. MMP-2 siRNA significantly abolished NE-induced FAK (Tyr397) phosphorylation and collagen-I expression. These findings suggest that the extracellular activation of MMP-2 accelerated collagen-I synthesis in rat cardiac fibroblasts and that FAK phosphorylation (Tyr397) plays a pivotal role in MMP-2-stimulated collagen-I synthesis.

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.

Large granular lymphocyte lymphoma in the skin and urinary bladder of a dog.

A 10-year-old female Cavalier King Charles Spaniel presented with hematuria, pollakiuria and skin rash. Based on the histopathological and cytological examination of the skin and bladder mucosa, the dog was diagnosed with large granular lymphocytic (LGL) lymphoma of the bladder and skin. The dog responded well to the initial chemotherapy with nimustine for 3 months. Since recurrence of skin erosion and bladder wall thickening were observed, the dog was subsequently administered chemotherapy with other anticancer drugs, including chlorambucil, vincristine, doxorubicin, L-asparaginase, cytosine arabinoside, and cyclophosphamide. The dog survived for 11 months and died due to tumor-related disseminated intravascular coagulation. This is the first report of a canine case of LGL lymphoma in the skin and bladder.

Spironolactone decreases isoproterenol-induced ventricular fibrosis and matrix metalloproteinase-2 in rats.

Although transregulation between the sympathetic nervous system and the renin-angiotensin-aldosterone system has been reported, it remains unclear whether sympathetic hyperactivity-induced matrix metalloproteinease (MMP) expression/activity and cardiac fibrosis are mediated by the mineralocorticoid receptor system. We investigated whether isoproterenol (ISO)-induced MMP expression/activity and cardiac fibrosis are mediated by spironolactone in rats. Male Wistar Kyoto rats were divided into 3 groups: control, ISO, and ISO combined with spironolactone (SPI). ISO (2.0 mg/kg/d) and/or SPI (40 mg/kg/d) were given for 14 d. Echocardiography and hemodynamic measurements were recorded and hearts were excised. The myocyte cross-sectional and fibrotic area was evaluated via histopathological analysis. MMP-2 and collagen-I were analyzed by Western blotting and zymography. Compared with the controls, ISO significantly elevated the end-diastolic left ventricular (LV) pressure and the time constant of isovolumic relaxation and decreased the -dP/dt, while those of SPI co-treatment did not. ISO treatment induced significant increases in the fractional shortening and relative wall thickness, whereas SPI co-treatment significantly decreased relative wall thickness. Similarly, ISO significantly increased LV weight and myocyte cross-sectional and fibrotic area, which occurred concomitantly with the MMP-2 expression/activity and the expression of collagen-I. Moreover, ISO induced these features were significantly attenuated by SPI co-treatment. Our results suggest that ISO-evoked sympathetic hyperactivity induced LV fibrosis and MMP-2, which may be partially controlled via the mineralocorticoid receptor system.

Giardia and other intestinal parasites in dogs from veterinary clinics in Japan.

The present study is the first report that describes the national survey of intestinal parasites in private household dogs brought to veterinary clinics in Japan. A total of 2,365 fresh feces were collected. Giardia-specific coproantigen was examined by ELISA kit (SNAP(®) Giardia, IDEXX Laboratories, Inc.; Maine, USA). Other intestinal parasites were determined microscopically using the formalin-ethyl acetate sedimentation technique. According to age categories, Giardia duodenalis, Cystoisospora spp., Toxocara canis, Toxascaris leonina, and Strongyloides spp., at ≦6-months-old showed significantly (P < 0.0001, P < 0.001 or P < 0.01, respectively) higher prevalence compared to >6 months old (31.5% vs. 2.3%, 9.1% vs. 0.05%, 1.8% vs. 0.4%, 1.1% vs. 0%, and 1.1% vs. 0.05%, respectively). In clinical categories, prevalences of G. duodenalis (14.8%) and Cystoisospora spp. (4.7%) in symptomatic dogs were significantly (P < 0.05, respectively) higher than those in asymptomatic ones (7.9% and 1.6%, respectively). G. duodenalis and Cystoisospora spp. were dominant parasites in private household dogs in Japan, especially ≦6-month-old dogs.

Therapeutic changes of plasma N-terminal pro-brain natriuretic peptide concentrations in 9 dogs with patent ductus arteriosus.

The plasma N-terminal proBNP (NT-proBNP) concentration is measured for determining the diagnosis and severity of heart failure in dogs. However, it is still unclear whether measurements of circulating NT-proBNP levels provide clinical utility as an indicator of therapeutic efficacy. Thus, we investigated the surgical correction-related changes of plasma NT-proBNP concentrations in 9 dogs with patent ductus arteriosus (PDA). Physical examination, thoracic radiography and echocardiography were conducted both before and after surgery. Similarly, the plasma NT-proBNP concentrations were determined using an enzyme immunoassay for canine pro-BNP. The International Small Animal Cardiac Health Council (ISACHC) class and murmur grade were significantly improved after surgery compared with before surgery. Vertebral heart size (VHS) and cardiothoracic ratio (CTR) were significantly decreased after surgery. Fractional shortening was significantly decreased and relative wall thickness (RWT) was significantly increased after surgery. Furthermore, the plasma NT-proBNP concentrations were significantly decreased by surgical correction. The plasma NT-proBNP concentration showed significant positive correlation with the ISACHC class, murmur grade, VHS and CTR and significant negative correlation with the RWT. Therefore, measurement of plasma NT-proBNP levels can be used to monitor the effectiveness of therapies such as surgical correction of PDA.

Anti-inflammatory potency of oral disulfiram compared with dexamethasone on endotoxin-induced uveitis in rats.

To investigate potency of oral disulfiram (DSF) compared with that of dexamethasone (Dexa), on endotoxin-induced uveitis (EIU) in rats. The oral administration with 750 mg/kg DSF suppressed the number of inflammatory cells, protein concentration, and levels of tumor necrosis factor (TNF)-α, Nitric oxide (NO) and prostaglandin (PG) E2 in the aqueous humor and improved the histiologic status of the ocular tissue at 24 hr after lipopolysaccharide (LPS) injection. The anti-inflammatory potency of DSF oral administration was as strong as that observed with 0.5 mg/kg Dexa in the present study. The results suggest that DSF might pave the way for a novel therapeutic agent for the management of uveitis.

Surgical repair of a complete endocardial cushion defect in a dog.

OBJECTIVE: To describe surgical repair of a complete endocardial cushion defect (ECD) in a dog. STUDY DESIGN: Clinical report. ANIMAL: A 5-month-old, 9.2 kg male Shetland sheepdog. METHODS: Echocardiographic examination revealed an ostium primum atrial septal defect (ASD), an inlet ventricular septal defect (VSD), mitral regurgitation (MR) and tricuspid regurgitation (TR), and a complete ECD was diagnosed. Surgical correction was performed using cardiopulmonary bypass (CPB) via right atriotomy. A polytetrafluoroethylene (PTFE) patch was secured along the margin of the inlet VSD using simple continuous suture, then the cleft in the septal mitral leaflet was sutured. Similarly, the cleft in the septal tricuspid leaflets was sutured. To complete inlet VSD closure, the VSD patch was secured to these sutured leaflets by simple continuous suture. Another PTFE patch was used to close the ostium primum ASD. RESULT: After surgery, MR, TR, and interventricular shunting were decreased. The dog was alive 6 years and 5 months after the surgery with no evidence of an interventricular shunt, TR, or other clinical signs. CONCLUSIONS: Complete ECD in a dog was corrected using a 2-patch technique under CPB.

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.

Differences in the duration of diuretic effects and impact on the renin-angiotensin-aldosterone system of furosemide in healthy dogs.

Our aim was to investigate the differences in the duration of diuretic effects and impact on the renin-angiotensin-aldosterone (RAA) system of furosemide as a model of short- and long-acting loop diuretics. Anesthetized dogs (n=6) were randomized into placebo, intravenous bolus administration (IB) and chronic rate infusion (CRI) groups. This study was conducted with a crossover study. Furosemide (4 mg/kg) was diluted to 18 mL in sterile saline. Furosemide was infused at 0.5 mg/kg/hr for 8 hr in the CRI group or was injected at 0 and 4 hr (both 2 mg/kg) in the IB group. Blood and urine samples were collected at baseline and at 1, 2, 4, 5, 6 and 8 hr. Compared with the baseline, the IB group had a significantly increased urine output at 1 and 5 hr. The CRI group had a significantly increased urine output persisting for 4 hr compared with the baseline. Compared with the placebo group, 8-hr urine output and 8-hr sodium excretion were significantly increased in the IB and CRI groups; the values in the CRI group were significantly higher than those in the IB group. Eight-hour potassium excretion was significantly increased in the IB and CRI groups. The plasma aldosterone concentration was significantly elevated in the IB group at 8 hr. Duration of action may be a predominant cause of loop diuretic-related differences. Persistent diuresis may cause greater diuretic effects than transient diuresis, with less elevation of the plasma aldosterone concentration.

Usefulness of pericardial lung ultrasonography for the diagnosis of cardiogenic pulmonary edema in dogs.

OBJECTIVE: To investigate whether lung ultrasonography (LUS) performed around the heart, where the lungs are in contact with the pericardium (ie, pericardial LUS), could be used for the diagnosis of cardiogenic pulmonary edema (CPE) in dogs with degenerative mitral valve disease (DMVD). ANIMALS: 15 control dogs with healthy hearts and 26 dogs with DMVD. PROCEDURES: In a prospective multicenter study design, dogs with DMVD were assigned to 2 groups: those with CPE (n = 11) and those without CPE (15). Thoracic radiography, echocardiography, and pericardial LUS were performed for all dogs. For pericardial LUS, the left ventricular short-axis view was obtained with a sector probe (dog positioned in right parasternal recumbency) and the number of B lines was recorded. Accuracy of pericardial LUS for the diagnosis of CPE was calculated, with thoracic radiography used as the reference standard. RESULTS: On thoracic radiography, all dogs with CPE had a diffuse distribution of interstitial to alveolar pulmonary infiltrates. On pericardial LUS, most control dogs (14/15) and dogs with DMVD but no CPE (13/15) had ≤ 2 B lines, whereas all dogs with DMVD and CPE had ≥ 3 B lines. The presence of ≥ 4 B lines had high sensitivity (91%; 95% confidence interval, 62% to 98%) and excellent specificity (100%; 95% confidence interval, 89% to 100%) for the diagnosis of CPE, and the area under the receiver operating characteristic curve was 0.99. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that identification of ≥ 4 B lines extending from the epicardium of the left ventricle into the lung field on pericardial LUS may be useful in the diagnosis of CPE in dogs with DMVD. Additional research is needed to determine whether pericardial LUS allows differentiation between CPE and pneumonia.

Evaluation of atrial natriuretic peptide and cardiac troponin I concentrations for assessment of disease severity in dogs with naturally occurring mitral valve disease.

OBJECTIVE: To evaluate and compare the clinical usefulness of plasma atrial natriuretic peptide (ANP) and cardiac troponin-I (cTnI) concentrations for assessment of disease severity in dogs with naturally occurring mitral valve disease (MVD). ANIMALS: 316 dogs with MVD and 40 healthy control dogs. PROCEDURES: Each dog underwent a physical examination and echocardiographic and thoracic radiographic assessments. Blood samples were obtained and processed for measurement of plasma ANP and cTnI concentrations. Dogs with MVD were categorized into 3 groups (stages B1 [no clinical signs or evidence of cardiac enlargement], B2 [no clinical signs with evidence of cardiac enlargement], and C [history of congestive heart failure and pulmonary edema]) on the basis of American College of Veterinary Internal Medicine guidelines. Receiver operating characteristic curve analysis was used to evaluate the accuracy of plasma ANP and cTnI concentrations for assessment of MVD severity. RESULTS: Plasma ANP and cTnI concentrations increased as disease severity increased. Median plasma ANP concentrations for all 3 MVD groups and median plasma cTnI concentrations for the stage B2 and C groups were significantly greater than the corresponding concentrations for the control group. Plasma ANP concentration, but not cTnI concentration, appeared to be useful for detection of dogs with subclinical (stages B1 and B2) MVD, whereas both concentrations appeared useful for detection of dogs with stage C MVD. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that plasma ANP and cTnI concentrations should not be used independently to diagnose MVD but can be used to assess MVD severity and supplement echocardiographic findings.

Doxycycline attenuates isoproterenol-induced myocardial fibrosis and matrix metalloproteinase activity in rats.

Our objective was to investigate the effects of doxycycline, a matrix metalloproteinase (MMP) inhibitor (MMPi) on beta-agonist-induced myocardial fibrosis and MMP expression. Twenly-four Wistar-Kyoto rats were divided into 3 groups: control (CTL; n=8), isoproterenol (ISO; n=8), and isoproterenol with doxycycline (ISO+DOX; n=8). ISO and ISO+DOX rats received L-isoproterenol (2.0 mg/kg/d) for 14 d, whereas the CTL group received vehicle. In addition, ISO+DOX rats received a subcutaneous injection of doxycycline (25 mg/kg/d) for 14 d, whereas CTL and ISO rats were injected with saline. Cardiac fibrosis was evaluated via histopathological analysis. MMP-2 and -9 were analyzed by Western blotting and zymography. Compared to the control, the myocardial cross-sectional area and areas of fibrosis were increased significantly in the ISO group, but were attenuated in the ISO+DOX group. MMP-2 activity also increased significantly in the ISO group, but decreased in the ISO+DOX group. Similarly, immunoblotting showed significant increase in MMP-2 and -9 levels in the ISO group, and decreased levels in the ISO+DOX group. Our results suggest that the enhanced expression of MMPs plays a prominent role in promoting myocardial fibrosis in beta-agonist signaling pathway, and that MMP-inhibiting compounds may attenuate myocardial fibrosis.

The relationship between invasive hemodynamic measurements and tissue Doppler-derived myocardial velocity and acceleration during isovolumic relaxation in healthy dogs.

This study investigated the feasibility of using the values of tissue Doppler imaging (TDI)-derived myocardial velocity during isovolumic relaxation (V(IR)) and myocardial acceleration during isovolumic relaxation (ACC) obtained from the left ventricular (LV) free wall to evaluate LV relaxation in normal dogs. Seven dogs were anesthetized, and dobutamine or esmolol was infused at a rate of 5.0 and 10.0 mug/kg/min or 100 and 500 mug/kg/min, respectively, via a cephalic vein. The order of drug administration (dobutamine or esmolol) was assigned to each dog. Simultaneous pulsed-Doppler (PD) echocardiography, TDI and hemodynamic measurements were performed. Compared with the baseline values, dobutamine significantly increased dP/dt min, but significantly shortened tau (tau). Similarly, esmolol significantly decreased dP/dt min, but significantly prolonged tau. Compared with the baseline values, dobutamine significantly increased V(IR) and ACC, and esmolol significantly decreased V(IR) and ACC. Both dP/dt min and tau were significantly correlated with TDI-derived IVRT (r=-0.43 and 0.74), V(IR) (r=0.85 and -0.49) and ACC (r=0.84 and -0.52). These results indicate that the TDI-derived V(IR) and ACC values obtained from the LV free wall can potentially be used to assess LV relaxation in dogs.

Inotropic effects of a single intravenous recommended dose of pimobendan in healthy dogs.

We investigated the effects of an injectable pimobendan solution (0.15 mg/kg) on cardiac function in healthy dogs. Fifteen dogs were divided into placebo, intravenous pimobendan injection, and subcutaneous pimobendan injection groups. In the placebo, the heart rate, systolic and end-diastolic left ventricular pressure (LVPs and LVEDP), and peak positive (max dP/dt) and negative (min dP/dt) first derivatives of the left ventricular pressure did not change for 60 min. After the intravenous pimobendan injection, LVEDP decreased significantly within 5 min, while the max dP/dt increased, and the effects continued until 60 min. In comparison, there were no hemodynamic changes after the subcutaneous pimobendan injection. This study demonstrates that injectable pimobendan induced a rapid inotropic effect and decreased the LVEDP in dogs.

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.

Assessing diastolic function with Doppler echocardiography using a novel index: ratio of the transmitral early diastolic velocity to pulmonary diastolic velocity.

We developed a novel index to assess left ventricular (LV) relaxation as the ratio of transmitral early diastolic velocity to pulmonary diastolic velocity (E/D ratio). Mixed breed dogs (n=7) were anesthetized and their respiration was controlled. A 3.5-Fr micromanometer-tipped catheter was placed into the left ventricle. Dobutamine (5.0 or 10 microg/kg/min) or esmolol (100 or 500 microg/kg/min) was administered via the cephalic vein. The transmitral flow (TMF) and pulmonary venous flow (PVF) were recorded using transthoracic echocardiography from the apical long-axis view. The heart rate, systolic LV pressure, +dP/dt, and -dP/dt were significantly elevated by dobutamine, but significantly reduced by esmolol. Dobutamine significantly decreased tau, whereas esmolol significantly increased tau. The TMF-derived E and PVF-derived D wave velocities increased significantly with dobutamine, but decreased significantly with esmolol. A significant correlation was detected between the E and D wave velocities (r=0.92). Consequently, the E/D ratio was decreased significantly with dobutamine, and increased significantly with esmolol. Furthermore, the E/D ratio was significantly correlated with -dP/dt (r= -0.64) and tau (r=0.84). Our results suggest that the E/D ratio reflects LV relaxation, and may potentially provide further information on LV relaxation.

Volume loading-related changes in tissue Doppler images derived from the tricuspid valve annulus in dogs.

OBJECTIVE: To investigate the relationship between preload and tricuspid valve annulus-derived tissue Doppler imaging (TDI) as an index of right ventricular (RV) filling in dogs. ANIMALS: 7 Beagles. PROCEDURES: Peak systolic RV pressure and RV end-diastolic pressure (RVEDP) were measured in anesthetized dogs. Pulsed Doppler was used to measure tricuspid valve inflow and pulmonary valve outflow velocities. The TDI velocities were measured at the lateral corner of the tricuspid valve annulus. Lactated Ringer's solution was infused at 200 mL/kg/h for 60 minutes via the cephalic vein. RESULTS: IV infusion significantly increased heart rate, RV pressure, and RVEDP. Early diastolic flow (E-wave) and ejection time significantly increased. The myocardial performance index (MPI) significantly decreased. Intravenous infusion significantly increased the ratio of the E'-wave (peak myocardial velocity during early diastole) to the A'-wave (peak myocardial velocity during late diastole; E':A' ratio) and myocardial velocity during systole (S'), early diastole (E'), and late diastole (A'). The TDI-isovolumic relaxation time and TDI-MPI decreased significantly. The RVEDP was correlated with late diastolic flow (A-wave), ratio of the E-wave to the A-wave (E:A ratio), E'-wave, A'-wave, S'-wave (peak myocardial velocity during systole), TDI-isovolumic relaxation time, TDI-MPI, and ratio of the E-wave to the E'-wave (E: E' ratio). The A-wave and E:A ratio and TDI-derived isovolumic relaxation time, S' duration, and E'-wave could predict the RVEDP. CONCLUSIONS AND CLINICAL RELEVANCE: The TDI velocities were affected by RV filling pressure in healthy dogs, whereas other TDI profiles, such as MPI and E':A' ratio, were independent of acute filling abnormalities.