MEDizzy - A 66-year-old man with a long history of heart failure was

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Drugs for Cardiac Failure

A 66-year-old man with a long history of heart failure was admitted to the hospital because of a heart failure exacerbation. His current medications included furosemide, captopril, and carvedilol. On admission, the patient showed the following hemodynamic profile: blood pressure 100/60 mm Hg, pulse 118/min, cardiac output 2.6 L/min. Physical examination confirmed the diagnosis of acute heart failure, and an intravenous infusion of milrinone was started. Which of the following molecular events most likely mediated the positive inotropic action of the drug?

ExplanationA patient with acute decompensated heart failure usually needs positive inotropic agents. Because the patient was using β-blockers, phosphodiesterase inhibitors are preferred over dobutamine. Phosphodiesterase inhibitors inhibit the cyclic adenosine monophosphate (cAMP) phosphodiesterase 3 isozyme with a resulting increase in cAMP levels. The cascade of events that follows this increase is equal to that triggered by other inotropic drugs (β1 agonists, glucagon, etc.), which also increase (although by a different mechanism) cAMP levels. It involves opening of voltage-gated Ca2+ channels, which in turn increases intracellular Ca2+ levels.