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.

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 smooth muscle.^1-4,8

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.