Short-term hemodynamic and neuroendocrine effects of pimobendan and benazapril in dogs with myxomatous mitral valve disease and congestive heart failure.

BACKGROUND: Pimobendan and benazepril are frequently used with diuretics to treat dogs in congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). AIM: To compare the short-term effects of pimobendan versus benazepril on pump function, heart size, and neuroendocrine profile in dogs with CHF caused by MMVD. ANIMALS: Sixteen client-owned dogs. MATERIAL AND METHODS: Seven-day prospective single-blinded study of dogs stabilized on furosemide monotherapy, randomized to pimobendan (0.4-0.6 mg/kg/day) or benazepril (0.25-1.0 mg/kg/day). Dogs had first-pass radionuclide angiocardiography, and heart size was measured by radiography and echocardiography. Circulating neuroendocrine hormones were measured. RESULTS: Baseline variables did not differ between treatment groups. Greater decreases in the pimobendan than in the benazepril group were found for heart rate (P = .001), heart rate-normalized pulmonary transit time (P = .02), left atrial size (P = .03), and systolic and diastolic left ventricular diameters (P < .001 and P = .03, respectively) and volumes (P < .001 and P = .02, respectively), whereas ejection fraction increased more (P = .02) in the pimobendan group. Of the neuroendocrine hormones, only N-terminal proatrial natriuretic peptide (NT-ProANP) differed (P = .04) between groups. Within groups, plasma aldosterone increased (P = .01), and NT-proANP (P = .01) and NT-proB-type (P = .02) natriuretic peptide decreased in the pimobendan group, and NT-proANP (P = .02) and plasma vasopressin (P = .01) decreased in the benazepril group. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan improves short-term cardiac function more than benazepril in dogs with CHF caused by MMVD. Pimobendan treatment enables the heart to work at smaller end-systolic and diastolic dimensions while maintaining adequate forward stroke volume. Some of the treatment responses found in neuroendocrine profile might have therapeutic relevance.

Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats.

The objectives of these investigations were: first, to describe the pharmacokinetic properties of meloxicam in cats following single and multiple oral administration and secondly, to simulate different oral dosage regimes for meloxicam in cats after multiple dose administration to illustrate and evaluate those dosage regimes for the alleviation of inflammation and pain in cats. Six healthy domestic short hair cats were treated orally with various dosage regimes (0.05-0.2 mg/kg/day). Plasma samples were collected at predefined times and quantitatively analysed using liquid/liquid extraction followed by reverse phase HPLC with UV-detection. Meloxicam plasma concentration data were analysed using the population pharmacokinetic approach (software: NONMEM). The final model was used to simulate different dosage regimes. The plasma concentration-time profiles of meloxicam in cats after oral single and multiple dose administration were best described by an open one-compartment model with first-order absorption and first-order elimination. Pharmacokinetic parameters were estimated to be 0.00656 L/h/kg for the total apparent body clearance (CL/F), 0.245 L/kg for the apparent volume of distribution (V/F), 1.26 1/h for the absorption constant (K(A)) and 25.7 h for the mean plasma terminal half-life. Simulations showed that the median trough steady-state concentrations of 228 ng/mL were reached after five, one or 6 days following a single initial dose of 0.05, 0.1 and 0.2 mg/kg each followed by 0.05 mg/kg/day.

Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. HYPOTHESIS: Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. ANIMALS: Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. METHODS: A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. RESULTS: Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.

Comparison of different transition metal ions for immobilized metal affinity chromatography of selenoprotein P from human plasma.

Cu2+, Ni2+, Zn2+, Co2+ and Cd2+ were evaluated in metal ion affinity chromatography for enrichment of selenoprotein P, and immobilized Co2+ affinity chromatography was found to be the most selective chromatographic method. The chromatography was performed by fast protein liquid chromatography and the fractionation was followed by analysis of the collected fractions for selenium by inductively coupled plasma mass spectrometry. By the combination of immobilized Co2+ affinity chromatography and heparin affinity chromatography a simple method was developed yielding a 14,800-fold enrichment of selenoprotein P. The purity of the protein was determined by SDS-PAGE and by sequencing from polyvinylidene difluoride blots of SDS-PAGE gels.

Detection of metallothionein isoforms from three different species using on-line capillary electrophoresis-mass spectrometry.

An on-line capillary electrophoresis-mass spectrometry method (CE-MS) for the detection of metallothionein (MT) isoforms is described. The detected masses were usually within 1-1.5 mass units of the expected molecular weights. MT-containing samples from rabbit, sheep, and yeast (Saccharomyces cerevisiae) were subjected to CE-MS analysis. The analysis of rabbit liver MT revealed the masses of 10 proteins/peptides. Five of the detected masses corresponded well with the expected masses calculated from the amino acid sequence of previously described MT isoforms, one was suspected to be a deacetylated form of MT-2A, one was presumed to be a yet unknown isoform, and three masses were classified as non-MT compounds. From the analysis of a fetal sheep liver extract six proteins were detected of which three masses corresponded to previously described MT isoforms. Two purified MT subforms from S. cerivisiae (encoded by the CUP1 locus) were analyzed for their copper content and both forms were found to contain eight copper atoms per molecule.

Simultaneous determination of chromium(III) and chromium(VI) in aqueous solutions by ion chromatography and chemiluminescence detection.

A method for the simultaneous determination of chromium(iii) and chromium(vi) in a flow system based on chemiluminescence was developed. A Dionex cation-exchange guard column was used to separate chromium(iii) from chromium(vi), and chromium(vi) was reduced by potassium sulfite, whereupon both species were detected by use of the luminol-hydrogen peroxide chemiluminescence system. Linear calibration for both species was established over the concentration range 1-1000 micrograms l-1. The precision at the 20 micrograms l-1 level was 3.5% for chromium(iii) and 3.3% for chromium(vi), respectively. The detection limit was 0.5 micrograms l-1 for both species. Data were in agreement with Zeeman-effect background corrected atomic absorption spectrometry measurements.

Testing the adequacy of equilibrium models for complex formation Complexation between molybdate and oxalate revisited.

In potentiometric studies of metal-ligand equilibria a given model is tested by adjustment of the corresponding stability constants with the purpose of obtaining as good a fit as possible to the experimental data. When judging the goodness-of-fit it is of great importance to be in control of any possible systematic error in concentrations or electrode parameters. The molybdate-oxalate system is used to demonstrate how one crucial parameter influences the evaluations of goodness-of-fit. The system is simple, having only one complex species, MoO(3)oxal(2-), with logarithmic stability constant 13.816 in the pH-range 4-7.

Exposure to chromium from hospital cleaning.

The relevance of a positive chromium patch test in females with hand eczema is very often obscure. In order to investigate the exposure to chromium in an everyday event as cleaning, the chromium content of water samples from various steps of the cleaning process in a Danish hospital was analyzed. During cleaning the chromium contamination increased above the theoretical limit necessary for sensitization. House dust contains considerable amounts of chromium, and will readily liberate it into suspension. All the chromium was found in the trivalent form.