Inotropy

Inotropy refers to the force of muscular contraction, especially the contractile strength of the heart. It is distinct from chronotropy (heart rate) and lusitropy (relaxation). Inotropy describes the intrinsic ability of cardiac muscle to generate force at a given preload and afterload and can be modified by autonomic input and pharmacologic agents. Positive inotropy increases contractile force, while negative inotropy decreases it.

Mechanisms governing inotropy center on intracellular calcium handling and myofilament sensitivity. Positive inotropy usually involves increased calcium availability during systole and enhanced myofilament responsiveness to calcium. The canonical pathway is beta-adrenergic stimulation, which raises cyclic AMP and activates protein kinase A, leading to greater L-type calcium current, enhanced calcium-induced calcium release, and improved reuptake and handling of calcium by the sarcoplasmic reticulum. Calcium sensitizers raise the myofilament response to calcium without large increases in intracellular calcium. Negative inotropy can result from reduced calcium availability, impaired calcium handling, or decreased myofilament sensitivity, as seen with electrolyte disturbances, acidosis, ischemia, certain drugs, or strong beta-blockade.

Clinical context and agents vary. Positive inotropes include dobutamine, dopamine, epinephrine, norepinephrine, milrinone, and, in some cases, levosimendan. Negative inotropes include beta-blockers, nondihydropyridine calcium channel blockers, and some antiarrhythmics. Inotropy is routinely assessed indirectly by measures of contractility such as ejection fraction or the rate of pressure rise in the ventricle (dP/dt). Inotropy is a central concept in understanding cardiac performance and is a key target in the management of heart failure and shock.