Direct Effects of Esmolol and Landiolol on Cardiac Function, Coronary Vasoactivity, and Ventricular Electrophysiology in Guinea-Pig Hearts

Abstract

Abstract. The ultra-short acting, selective β 1 -adrenergic antagonists landiolol and esmolol are widely used perioperatively; however, little is known about their acute direct actions on the heart. The current study utilized the Langendorff perfused heart system to measure changes in cardiac function and hemodynamics in response to each drug. Furthermore, electrophysiological analysis was performed on isolated ventricular myocytes. Direct application of esmolol significantly decreased systolic left ventricular pressure and heart rate at concentrations > 10 μM, while it dosedependently increased coronary perfusion pressure. Esmolol also shortened the action potential duration (APD) in a concentration-dependent manner, an action maintained even when the delayed rectifier K + current or ATP sensitive K + current was blocked. Moreover, esmolol inhibited both the inward rectifier K + current (I K1 ) and the L-type Ca 2+ current (I CaL ) and increased the outward current dose-dependently. In contrast, landiolol had minimal cardiac effects. In the Kyoto Model computer simulation, inhibition of either I K1 or I CaL alone failed to shorten the APD; however, an additional increase in the time-independent outward current caused shortening of the APD, equal to that induced by esmolol. In conclusion, esmolol directly inhibits cardiac performance significantly more so than landiolol, an effect revealed to be at least in part mediated by esmolol-induced APD shortening.

Safety and Efficacy of a Bolus Injection of Landiolol Hydrochloride as a Premedication for Multidetector-Row Computed Tomography Coronary Angiography

“…20, 21 Oral β-blocking agents are widely used to reduce HR, but they are not always sufficient. 22 Landiolol has similar pharmacological properties as esmolol, 23 but is short-acting and highly selective for β1 receptors, thus showing fewer side effects than other longer-acting β-blockers. 6,7 Recent studies have shown landiolol to be safe and effective in patients with perioperative atrial fibrillation or tachycardia, 9,11,13 in patients with severe ventricular arrhythmia 10 or acute decompensated heart failure, 11 and for early initiation of β-blockers in patients with acute myocardial infarction.…”

A Low-Dose β₁-Blocker Effectively and Safely Slows the Heart Rate in Patients with Acute Decompensated Heart Failure and Rapid Atrial Fibrillation

“…Landiolol is the most ultra-short-acting (t 1/2 : 4 min) intravenous β 1 -selective adrenergic receptor blocker (β 1 /β 1 ratio: 277) known; it has a significant chronotropic effect and little or no negative inotropic effect at low doses, as previously reported [13,15,16,17,18]. Even if the BP decreased with landiolol, it could be quickly restored to baseline levels by stopping its administration because it is a very-short-acting drug.…”

“…The important difference between esmolol and landiolol is that the latter has a greater chronotropic effect and a lesser inotropic effect than the former, as reported previously [13,15,16,17,18]. Recently, we reported that low-dose landiolol (1.5 µg·kg -1 ·min -1 ) safely decreased the HR in patients with severe ADHF and sinus tachycardia, thereby improving cardiac function, whereas high-dose landiolol (>3.0 µg·kg -1 ·min -1 ) suppressed cardiac function [13].…”

“…Continuous intravenous infusion of landiolol (1.0-2.0 µg·kg -1 ·min -1 ) or digoxin (0.25 mg) was then administered, and the ECG and BP were monitored for 24 h. Landiolol is an ultra-short-acting (elimination t 1/2 : 4 min) intravenous β-adrenergic receptor blocker that has a high β 1 selectivity (β 1 /β 2 = 277). Due to its ultra-short duration of activity [13,15,16,17,18], the acute hemodynamic changes were measurable immediately after landiolol was administered.…”

Effects of an hERG Activator, ICA-105574, on Electrophysiological Properties of Canine Hearts

“…However, effective potential in vivo is not always comparable to in vitro efficacy for off-target drugs, which have effects on autonomic nervous systems or multiple channels or metabolism, or have indirect effects on the hERG channel such as block of trafficking (16,26,27). In the in vivo experiments (Fig.…”