Modified Toyoda technique for total cystectomy and cutaneous ureterostomy in a cat.

OBJECTIVES: To report the technique and outcome of a cat treated with a total cystectomy and bilateral cutaneous ureterostomy. ANIMALS: A 16-year-old male castrated domestic shorthair cat. STUDY DESIGN: Case report. CASE PRESENTATION: A cat was referred after a 2-week history of pollakiuria and hematuria. Transitional cell carcinoma (TCC) was suspected based on ultrasonographic, cytologic, and contrast computed tomographic (CT) findings. A total cystectomy was combined with a modified cutaneous ureterostomy: the ureter, incised like a fish-mouth aperture, was anastomosed to the skin after the creation of a rectangular-shaped defect. Complete excision of a TCC was confirmed histologically. RESULTS: Ureteral stents were removed 7 days (left) and 28 days (right) postoperatively. The cat's incontinence was managed with an absorbent diaper surrounding the ureteral stomata. The right ureter became obstructed 14 months after surgery, and the cat died at home approximately 16 months after surgery. In spite of the urinary incontinence, the owner was satisfied with the surgery and evaluated the cat's quality of life as satisfactory. CONCLUSIONS: The total cystectomy and cutaneous ureterostomy described here allowed urinary excretion and resulted in long-term survival of a cat with bladder TCC.

Comparison of early posttreatment effects of two steroidal anti-inflammatory ophthalmic drugs on the ocular inflammatory response induced by paracentesis in healthy canine eyes.

OBJECTIVE: We investigated the early posttreatment effects of two steroidal anti-inflammatory ophthalmic drugs on blood-aqueous barrier (BAB) breakdown by paracentesis in dogs. ANIMAL STUDIES: We studied 21 healthy beagles with normal eyes. PROCEDURES: Controlled anterior chamber paracentesis (0.5 mL) was performed in one eye of each dog. Control group dogs (n = 7) received no medication, whereas those in the treatment groups received a topical anti-inflammatory medication (difluprednate [DFBA] ophthalmic emulsion 0.05% [n = 7] or betamethasone [BMZ] sodium phosphate ophthalmic solution 0.1% [n = 7]) at 0, 15, 30, and 45 minutes after initial paracentesis in the paracentesed eyes. Secondary aqueous humor (AH) was collected 60 minutes after initial paracentesis. Protein and prostaglandin E2 (PGE2 ) concentrations in AH were determined using the bicinchoninic acid assay and commercially available immunoassay kit, respectively. All mean values in the three groups were compared using analysis of variance followed by Tukey's post hoc test. RESULTS: Aqueous protein and PGE2 concentrations were markedly increased at 60 minutes following paracentesis. Both concentrations in the secondary AH of the DFBA group were significantly lower than those of the control group; however, treatment with BMZ had no significant effects. CONCLUSIONS: Early postparacentesis treatment with DFBA was more effective than that with BMZ for reducing aqueous protein and PGE2 contents in dogs with paracentesis-induced BAB breakdown. DFBA may be an appropriate treatment during the early stage of anterior uveitis caused by intraocular surgery in dogs.

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 %.

Selection of suitable reference genes for mRNA quantification studies using common marmoset tissues.

The common marmoset (Callithrix jacchus) is increasingly being used as a non-human primate animal model in biomedical research. To perform accurate quantitative analysis of gene expression by quantitative reverse transcription polymerase chain reaction, reliable reference genes should be selected. In this study, we evaluated the expressions of 11 widely used reference genes: ACTB, ATP5F1, B2M, GAPDH, HPRT1, PGK1, PPIA, RN18S1, RPLP0, TBP and UBC in 12 tissues and five brain areas of healthy common marmosets. NormFinder and geNorm indicated that the most suitable reference genes for cross-sectional studies of the 17 tissues were RN18S1 and RPLP0. Conversely, ACTB and PPIA were the most suitable for analyzing brain samples; however, the expression of PGK1 fluctuated among brain areas. These results indicate that suitable reference genes differ between the tissues examined. This study provides fundamental information for gene expression studies of the common marmoset and highlights the importance of validating reference genes before quantification of target mRNAs.

Effects of Intravenous Pimobendan on Cardiovascular Parameters in Healthy Sedated Cats.

This study aimed to investigate the effects of intravenous pimobendan on cardiovascular function and to determine the appropriate dose for clinical usage in cats. Six purpose-bred cats received one of the following treatments: intravenous pimobendan at a single dose of 0.075 mg/kg (low dose [LD] group), 0.15 mg/kg (middle dose [MD] group), 0.3 mg/kg (high dose [HD] group), or saline at 0.1 mL/kg (placebo group). Echocardiography and blood pressure measurements were performed before and 5, 15, 30, 45, and 60 minute after drug administration for each treatment. In the MD and HD groups, the fractional shortening, peak systolic velocity, cardiac output, and heart rate increased significantly. There were no significant differences in blood pressure among the groups. Intravenous pimobendan at 0.15-0.3 mg/kg increased the fractional shortening, peak systolic velocity, cardiac output in healthy cats.

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.

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.

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.

Comparison of regression for blood ALP levels using methods of the Japan Society of Clinical Chemistry and the International Federation of Clinical Chemistry and Laboratory Medicine in bovine, canine, feline, and human testing.

Livestock and companion animal health have a direct impact on human health. Research on clinical laboratory technology for veterinary medicine is as important as that on human laboratory technology. Reagents and analysis equipment for human medical laboratory tests are often used in veterinary medicine. Medical laboratories in Japan utilize the Japan Society of Clinical Chemistry (JSCC) method for blood alkaline phosphatase (ALP) analysis. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) method is used worldwide for ALP catalytic concentration measurement. When the IFCC method is used, human blood ALP activity is approximately one-third of the JSCC method's activity. The JSCC method for ALP measurement was switched to the IFCC method in medical laboratories in Japan in April 2020 for global standardization purpose. It is uncertain whether conventional JSCC method reagents will continue to be supplied. In veterinary medicine, the relationship between the JSCC and IFCC methods in terms of ALP measurement is almost unclear. This study investigated the regression between JSCC and IFCC methods measuring ALP in bovine, canine, feline, and human. The regression formulas for bovine, canine, feline, and human ALP values using the conventional JSCC (x) and IFCC (y) methods are y = 0.379x + 0.124, y = 0.289x + 8.291, y = 0.358x + 0.432, and y = 0.337x + 2.959, respectively. These results suggested that the IFCC method measurement could be estimated by approximately one-third of the JSCC method measurement in animal species such as bovine, canine, and feline. By applying the conversion factors proposed in this study, a very good correlation could be obtained between the two methods for each animal.

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.

Regression formula to predict the International Federation of Clinical Chemistry and Laboratory Medicine measure of alkaline phosphatase activity in canine blood based on the Japan Society of Clinical Chemistry reference method.

The Japan Society of Clinical Chemistry reference method (JSCC method) is used to measure alkaline phosphatase (ALP) activity only in Japan. Other countries use the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method to measure ALP activity. Since April 2020, human medical institutions in Japan have been gradually switching to the IFCC method. However, it is unclear whether the supply of reagents required for the JSCC method will be steady in the future. Additionally, the comparison of the performances and accuracies of these two methods for measuring ALP values remains uncertain in several animal species. In this investigation, we measured canine ALP activity using both methods and developed a formula to interconvert the two resulting values. The regression formula for ALP values measured using the modified JSCC (x) and IFCC (y) methods was determined as log10 y=0.960 log10 x-0.395 (r=0.997). However, the correlation between values based on JSCC and IFCC methods can change depending on the composition of ALP isozymes. Therefore, the developed formula can currently serve as a provisional strategy in calculating ALP levels. Nevertheless, this formula might avoid confusion in the clinical field during the transition from the JSCC to the IFCC method when both measurement values co-exist.

Characterization of feline serum ferritin-binding proteins: the presence of a novel ferritin-binding protein as an inhibitory factor in feline ferritin immunoassay.

Ferritin-binding proteins (FBPs) such as anti-ferritin antibody, alpha-2-macroglobulin, apolipoprotein B are expected to interact with circulating ferritin to eliminate it from circulation. However, we found that feline serum more strongly inhibits the detection of canine liver ferritin by immunoassay than its apoferritin; putative FBPs probably conceal ferritin epitopes detected by anti-ferritin antibodies. After complex formation between affinity-purified FBPs and canine liver ferritin, co-immunoprecipitates of the complex by anti-bovine spleen ferritin antibody were found to contain autoantibodies (IgG, IgM, and IgA) to ferritin by immunoblot analysis with antibodies specific for feline IgG, IgM, and IgA. On the other hand, affinity-purified samples did not show any inhibitory effect in the ferritin immunoassay. This result shows that feline serum has another FBP, which inhibits ferritin immunoassays, but not anti-ferritin autoantibody. A feline FBP was partially purified from feline serum by (NH(4))(2)SO(4) fractionation (33-50%), gel filtration chromatography, and anion exchange chromatography. After binding of the partially purified sample with canine liver ferritin coupled-Sepharose gel, the FBP was separated and purified from complexes formed in a native-PAGE gel. SDS-PAGE analysis showed that the purified FBP is a homomultimer composed of 31 kDa monomeric subunits connected by intermolecular disulfide bonds. Detection of feline liver ferritin by immunoassay was inhibited by FBP in a dose-dependent manner. The purified protein molecules appeared to be conglomerate of pentraxin-like molecules by its electron micrographic appearance. These results demonstrate that feline serum contains a novel FBP as inhibitory factor of ferritin immunoassay with different molecular properties from those of other mammalian FBPs, in addition to auto-antibodies (IgG, IgM, and IgA) to ferritin.

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.

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.

Relationships between velocities of pulmonary venous flow and plasma concentrations of atrial natriuretic peptide in healthy dogs.

OBJECTIVE: To investigate the relationship between velocities of pulmonary venous flow (PVF) and plasma concentrations of atrial natriuretic peptide (ANP) in healthy dogs. ANIMALS: 7 healthy Beagles. PROCEDURES: Dogs were anesthetized, intubated, and positioned in left lateral recumbency. Lactated Ringer's solution was infused (200 mL/kg/h) for 60 minutes via a cephalic vein. Transmitral flow and PVF velocities were measured echocardiographically by use of the apical 4-chamber view. Pulmonary capillary wedge pressure (PCWP) and ANP concentrations were determined. RESULTS: IV infusion significantly increased heart rate and PCWP. Similarly, the ANP concentration significantly increased from baseline (before infusion of lactated Ringer's solution) values. Transmitral flow velocities were significantly increased, although the ratio of velocity of the flow during early ventricular diastole (E wave) to velocity of the atrial flow (A wave; E:A ratio) was unchanged. Regarding the PVF velocities, forward flow during ventricular systole (S wave) and retrograde flow during atrial contraction were significantly increased, whereas velocity of the forward flow during ventricular diastole (D wave) was unchanged. Ratio of the velocity of the S wave to velocity of the D wave was increased significantly, and this ratio was significantly correlated with PCWP or ANP concentration. However, the E:A ratio was not correlated with PCWP or ANP concentration. CONCLUSIONS AND CLINICAL RELEVANCE: PVF velocities were strongly correlated with PCWP and plasma ANP concentration in clinically normal dogs. Therefore, PVF velocities may serve as a sensitive indicator and provide additional information for monitoring acute preloading conditions and estimating atrial filling abnormalities in dogs.

Assessment of diuretic effects and changes in plasma aldosterone concentration following oral administration of a single dose of furosemide or azosemide in healthy dogs.

OBJECTIVE: To determine the diuretic effects and changes in plasma aldosterone concentration (PAC) following oral administration of a single dose of furosemide or azosemide in healthy dogs. ANIMALS: 8 mixed-breed dogs. PROCEDURES: A single dose of furosemide (2 mg/kg), azosemide (1, 5, or 10 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally (in random order at 7-day intervals) to each dog (5 treatments/dog). Urine and blood samples were collected before (2 hours after evacuation of the urinary bladder; baseline) and at intervals for 24 hours after drug treatment to assess urine volume and plasma and urine biochemical variables. RESULTS: Compared with baseline values, treatment with furosemide and azosemide (5 and 10 mg/kg) increased urine output for 1 to 2 hours and 2 to 4 hours, respectively. The 24-hour urine volume and urinary sodium excretion were significantly increased following furosemide and azosemide (5 and 10 mg/kg) treatments, compared with effects of placebo; these increases were dose dependent for azosemide, and increases were similar for furosemide and the 5 mg/kg dose of azosemide. Compared with other treatments, 24-hour urinary potassium excretion was significantly increased with azosemide at 10 mg/kg. Azosemide (5 and 10 mg/kg) significantly increased plasma total protein concentration and decreased plasma potassium concentration, compared with baseline values. Compared with the effect of placebo, PAC was significantly increased by furosemide and the 10 mg/kg dose of azosemide. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, a moderate dose of azosemide caused sufficient diuretic action and increased PAC to a lesser extent than furosemide.