Pimobendan: Understanding its cardiac effects in dogs with myocardial disease


Pimobendan: Understanding its cardiac effects in dogs with myocardial disease

When used in conjunction with other cardiac drugs, pimobendan, unapproved for use in the United States, may benefit dogs with congestive heart failure secondary to dilated cardiomyopathy or valvular insufficiency.


  • Pimobendan has positive inotropic and vasodilator effects in dogs.
  • Beneficial in dogs with advanced dilated cardiomyopathy or mitral valve disease, pimobendan is administered along with other cardiac drugs, such as ACE inhibitors, furosemide, or digoxin. It should not be used as sole therapy.
  • It is given orally at a dosage of 0.2 to 0.6 mg/kg daily divided into two doses given 12 hours apart.
  • Few adverse effects have been observed in dogs receiving the drug.
  • It has been used in some countries in Europe for several years and is undergoing studies in dogs in the United States.

Pimobendan (Vetmedin—Boehringer Ingelheim), 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 is approved for use in dogs to treat congestive heart failure originating from valvular insufficiency or dilated cardiomyopathy in some countries in Europe and in Canada, Mexico, and Australia and is currently undergoing Food and Drug Administration (FDA) review in the United States.

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 Cardiac muscle is distinct from skeletal and smooth muscle in that it relies on both extracellular and intracellular calcium sources for muscle contraction. Increases in cyclic adenosine monophosphate (camp), either from beta-adrenergic stimulation or phosphodiesterase iii inhibition, promote the opening of l-type calcium channels in cardiac myocytes and result in an influx of a small concentration of extracellular calcium ions at t tubule foot plates close to the sarcoplasmic reticulum. The small influx of extracellular calcium ions causes the release of a large concentration of calcium ions from the ryanodine receptors of the sarcoplasmic reticulum into the cytosol.5 The cytosolic calcium ions are immediately bound by the protein calmodulin.5 Calmodulin activates muscle contraction by delivering calcium ions to troponin c, a protein of the thin myofilaments of cardiac muscle.

Excitation-contraction coupling is an energy-consuming process requiring hydrolysis of adenosine triphosphate (ATP).2 Muscle contraction results from the interrelationship of four proteins: actin, myosin, troponin, and tropomyosin. The polymerization of actin and myosin results in sarcomere shortening and is inhibited by tropomyosin, troponin I, and ATP at rest.5 When calcium ions bind to troponin C, a steric conformational change occurs in the troponin-tropomyosin complex, troponin I inhibition of myosin adenosinetriphosphatase (ATPase) is removed, and ATP is hydrolyzed,5 which initiates contraction through the ratcheting action of actin over myosin.2