Pimobendan is an inodilator used in the treatment of canine congestive heart failure (CHF). The aim of this study was to investigate the pharmacokinetics and cardiovascular effects of a nonaqueous oral solution of pimobendan using a single-dose, operator-blinded, parallel-dose study design. Eight healthy dogs were divided into two treatment groups consisting of water (negative control) and pimobendan solution. Plasma samples and noninvasive measures of cardiovascular function were obtained over a 24-h period following dosing. Pimobendan and its active metabolite were quantified using an ultra-high-performance liquid chromatography-mass spectrometer (UHPLC-MS) assay. The oral pimobendan solution was rapidly absorbed [time taken to reach maximum concentration (Tmax ) 1.1 h] and readily converted to the active metabolite (metabolite Tmax 1.3 h). The elimination half-life was short for both pimobendan and its active metabolite (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2-4 h after a single oral dose, with measurable effects occurring primarily in echocardiographic indices of systolic function. Significant effects persisted for <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.
Background
The effects of synthetic brain natriuretic peptide (BNP1‐32) on cardiorenal and renin angiotensin aldosterone system in dogs with naturally occurring congestive heart failure (CHF) are unknown.
Objectives
To evaluate the cardiorenal and endocrine effects of SC administered synthetic canine BNP1‐32, with or without furosemide, in dogs with CHF caused by myxomatous mitral valve disease (MMVD).
Animals
Seven client‐owned male dogs with compensated American College of Veterinary Internal Medicine stage C CHF caused by MMVD on chronic treatment with furosemide, benazepril, and pimobendan.
Methods
A single‐dose, crossover, pilot study. Each dog received a dose of BNP1‐32 (5 μg/kg), furosemide (2 mg/kg), and both BNP1‐32/furosemide (5 μg/kg and 2 mg/kg, respectively) SC with a 2‐week washout period among each treatment. Between‐ and within‐treatment effects were evaluated using linear mixed modeling with restricted maximum likelihood estimation and evaluation of least square differences.
Results
Rapid absorption of BNP1‐32 and a corresponding rise in urinary cyclic guanosine monophosphate excretion was observed at 1‐2 hours after any treatment containing BNP1‐32 (P < .05). However, BNP1‐32 did not influence measured cardiorenal variables. Plasma aldosterone concentrations were below quantifiable levels in majority of the samples.
Conclusions and Clinical Importance
No beneficial cardiorenal effects were detected. It is possible that dogs with chronic CHF have a reduction in natriuretic peptide responsiveness.
The mean systemic filling pressure (MSFP) represents an interaction between intravascular volume and global cardiovascular compliance (GCC). Intravascular volume expansion using fluid resuscitation is the most frequent intervention in intensive care and emergency medicine for patients in shock and with haemodynamic compromise. The relationship between dynamic changes in MSFP, GCC and left ventricular compliance is unknown. We conducted prospective interventional pilot study following euthanasia in post cardiotomy adult sheep, investigating the relationships between changes in MSFP induced by rapid intravascular filling with fluids, global cardiovascular compliance and left ventricular compliance. This pilot investigation suggested a robust correlation between a gradual increase in the intravascular stressed volume from 0 to 40 ml/kg and the MSFP r = 0.708 95% CI 0.435 to 0.862, making feasible future prospective interventional studies. Based on the statistical modelling from the pilot results, we expect to identify a strong correlation of 0.71 ± 0.1 (95% CI) between the MSFP and the stressed intravascular volume in a future study.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.