Editors' note: This article is an updated excerpt from "Pimobendan: Understanding its cardiac effects in dogs with myocardial
disease," which appeared in Veterinary Medicine's October 2006 issue.
Pimobendan, a benzimidazole-pyridazinone drug, is classified as an inodilator because of its nonsympathomimetic, nonglycoside
positive inotropic (through myocardial calcium sensitization) and vasodilator properties.1-4 As such, pimobendan increases ventricular contractility and reduces preload and afterload in patients with advanced cardiac
insufficiency. Pimobendan (Vetmedin—Boehringer Ingelheim Vetmedica) is now approved in the United States for use in dogs to
manage signs of mild, moderate, or severe congestive heart failure originating from atrioventricular valvular insufficiency
or dilated cardiomyopathy.
To understand the pharmacology and therapeutic potential of pimobendan, clinicians should be familiar with the mechanisms
of cardiac muscle contraction in healthy and diseased hearts.
Myocardial contraction (i.e. excitation-contraction coupling) begins when a depolarization wave reaches a myocyte.2 In excitation-contraction coupling, action potentials depolarize cardiac muscle cell membranes, with phase 2 of the action
potential triggering calcium release from the sarcoplasmic reticulum.5 Normal cardiac muscle is distinct from skeletal and smooth muscle in that it relies on both extracellular (L-type calcium
channels) and intracellular (sarcoplasmic reticulum) calcium sources for muscle contraction.
Myocardial failure, best typified by dilated cardiomyopathy, is characterized by alterations of myocyte integrity and severely
disturbed intracellular calcium handling.6 Cytosolic calcium ion concentrations are adequate, but the sensitivity of troponin-C to calcium ions is impaired.6,7
PHARMACOLOGY OF PIMOBENDAN
Pimobendan's principal inotropic mechanism is troponin-C calcium sensitization, and this positive inotropic effect is accomplished
with only a small increase in myocardial energy consumption. Pimobendan also causes peripheral arteriolar dilation, coronary
artery dilation, pulmonary artery dilation, and peripheral venodilation by inhibiting phosphodiesterases III and V in vascular
USE IN DOGS
Pimobendan treatment is initiated in symptomatic dogs with congestive heart failure that may benefit from positive inotropic
action. The total dose is 0.5 mg/kg daily, which is divided into two doses (not necessarily equal) given 12 hours apart.9 The Vetmedin chewable tablet sizes are 1.25, 2.5, and 5 mg. The tablets are scored, and the calculated dose should be given
to the nearest half-tablet increment.
Advanced dilated cardiomyopathy
Pimobendan's strongest indication is to treat patients with advanced dilated cardiomyopathy because they have poor left ventricular
systolic function and reduced ejection fraction. They are subject to increased afterload as a result of dilation of the left
ventricle with inadequate wall hypertrophy and arteriolar constriction (caused by activation of the renin-angiotensin-aldosterone
system and increased plasma norepinephrine concentrations). This increased afterload negatively affects stroke volume and
ejection fraction. Through phosphodiesterase III and V inhibition, pimobendan promotes both arteriolar and venous dilation,
reducing afterload and preload, respectively.
We administer pimobendan in dogs with cardiomyopathy in the face of overt or impending congestive heart failure. Clinical
findings consistent with impending congestive heart failure include a gallop heart sound, atrial fibrillation, and nocturnal
dyspnea. Pulmonary or hepatic vein distention on radiographic and ultrasonographic examination is also consistent with impending
congestive heart failure.
Degenerative mitral valve disease
Patients with degenerative mitral valve disease have good contractility as assessed by echocardiography, even when the left
heart is severely dilated. Thus, the inotropic action of pimobendan would seem to be of little value. However, the vasodilator
action may contribute to preload and afterload reduction.