The negative inotropic effect of esmolol on isolated cardiac muscle

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Abstract
Esmolol is an ultra-short-term acting beta adrenergic blocker for intravenous use. The most common side effect is hypotension, which is often manageable by careful titration of the dose. We speculated whether esmolol had a direct negative inotropic effect on the cardiac muscle. Papillary muscles and trabeculae were excised from guinea pig and pig hearts. Force production was recorded together with action potentials. Membrane currents were recorded in isolated myocytes. The effects of two concentrations of esmolol were tested (55 and 110 micromol/L). Esmolol reduced action potential duration and plateau voltage, and decreased force production of isolated cardiac muscle. Voltage-clamp experiments from a holding potential of -40 mV and a step change to 0 mV showed a reduction in the inward current due to esmolol. Apart from being a beta adrenergic blocker esmolol also exerts a direct negative inotropic effect on cardiac muscle due to its inhibition of the calcium current during the action potential.