Cardiovascular effects of milrinone

Heart failure is caused by the inability of the heart to pump sufficient blood to supply necessary oxygen and nutrients to the tissues of the body. Drugs used to treat heart failure typically increase the force of cardiac contractions (positive inotropic effect). An additional desirable quality in a drug for the treatment of this condition would be that it relax the smooth muscle of the vascular system (vasodilator effect). A newly available drug, milrinone, appears to have both beneficial qualities. It acts by inhibiting the enzyme phosphodiesterase III in the metabolic degradation of cyclic adenosine monophosphate (cAMP); the increased levels of cAMP in the heart and vascular tissue lead to increased contractility of the heart and decreased contractility of blood vessels. Consequently, the heart muscle contracts more vigorously, and the blood vessels relax. Experiments performed in healthy control subjects and in patients with severe end-stage heart failure indicate that the therapeutic effects of milrinone (such as increased cardiac stroke volume, decreased systemic vascular resistance, and improvement in clinical symptoms of heart failure) are due to a combination of the positive inotropic and vasodilator effects. Administration of a compound with purely vasodilatory actions resulted in a much less dramatic alteration of the physiologic variables related to heart failure. With other drugs used to treat heart failure, notably beta adrenergic receptor-stimulating (beta agonist) drugs, there is a progressive desensitization to the effects of the drug; this results from a decrease in the number of cell-surface beta receptors. No such effect has been observed with milrinone administration, and this drug continues to be effective for prolonged periods of time. (Consumer Summary produced by Reliance Medical Information, Inc.)