Levosimendan infusion improves cardiac output but not blood pressure in a rodent model of severe metoprolol toxicity

Abstract

Levosimendan (Levo) is an inodilator improving cardiac output (CO) and reducing afterload in heart failure. Previously, we reported that Levo improved CO but not blood pressure (BP) in a rodent model of verapamil poisoning. We theorised that Levo-induced vasodilation should not influence BP to a similar degree in metoprolol poisoning. Aim: To assess the effect of Levo on haemodynamics in a rodent model of metoprolol poisoning. Method: Anaesthetized male Wistar rats were infused metoprolol continuously. When the BP dropped to 50% of baseline (time 0) rats received 1 of the 4 treatments: (a) control (0.9% saline bolus + infusion); (b) Levo-l (Levo 36 μm/kg loading dose followed by 0.6 μm/kg/min); (c) Levo-I (Levo infusion only at 0.6 μm/kg/min); and (d) Epi (epinephrine 0.5 μm/kg/min). All groups received comparable fluid volumes. Haemodynamics were recorded every 10 min for 70 min. CO, mean arterial pressure (MAP) and heart rate (HR) of each group were compared to the control. Results: All groups had comparable baseline and time 0 HR, MAP and CO. Levo-L and Levo-I rats showed significantly greater CO at t = 10 min ( p > 0.02 and p > 0.04, respectively). CO was higher at all other time points for both Levo groups. This was not statistically significant. Levo did not improve MAP compared to control. Adrenaline increased MAP but not CO compared to control and Levo groups. Conclusion: Levo did not improve MAP but moderately improved CO compared to control in this model of metoprolol poisoning. The response was similar to that reported previously in verapamil-poisoned rats. The improvement in MAP seen with epinephrine was most likely vasoconstriction mediated.