Purpose: We compared the negative chronotropic and inotropic effects of landiolol and esmolol, two clinically available short-acting beta1-blockers with high beta1-selectivity, using whole isolated rabbit heart preparations.
Methods: Tachycardia was induced by continuous perfusion of 10(-7) M isoproterenol, and we used concentrations of landiolol or esmolol in ascending steps (1 . 10(-6), 3 . 10(-6), 1 . 10(-5), 3 . 10(-5), and 1 x 10(-4) M). Heart rate (HR), left ventricular developed pressure (LVDP), the maximal rates of left ventricular force development (LVdP/dt(max)), and myocardial oxygen consumption (MVO2) were measured and compared.
Results: Both landiolol and esmolol produced dosedependent decreases in HR, LVDP, LVdP/dt(max), and MVO2. The HR lowering effects of the two agents were comparable. At concentrations of 3 . 10(-5) and 1 . 10(-4) M, esmolol produced more profound depression of LVDP (47 +/- 26 and 12 +/- 11 mmHg, respectively; mean +/- SD) and reduction of LVdP/dt(max) (650 +/- 287 and 120 +/- 103 mmHg x s(-1)) than landiolol (68 +/- 20 and 64 +/- 20 mmHg, and 897 +/- 236 and 852 +/- 240 mmHg.s(-1), respectively). At the same concentrations, esmolol caused more profound reduction in MVO(2) (40 +/- 11 and 35 +/- 10 microl x min(-1) x g(-1)) than landiolol (50 +/- 8 and 48 +/- 8 microl x min(-1) x g(-1)), respectively.
Conclusion: Our results indicate that in the isolated rabbit heart, landiolol and esmolol had equipotent negative chronotropic effects, however, landiolol had a less potent negative inotropic effect than esmolol.