Levosimendan Does Not Improve Cardiac Output or Blood Pressure in a Rodent Model of Propranolol Toxicity When Administered Using Various Dosing Regimens

Abstract

Background: Levosimendan (CAS: 141505-33-1) is a myocardial calcium sensitizer that improves myocardial contractility in various forms of heart failure. It produces a moderate improvement in cardiac output (CO) without an improvement in blood pressure (BP) in verapamil and metoprolol poisoned rodents. Aim: To assess the effect of various levosimendan dosing regimens on hemodynamics in a rodent model of propranolol poisoning. Method: Male Wistar rats (350-450 g) were anesthetized, ventilated, and instrumented to record BP, heart rate (HR), and CO. Propranolol was infused continually. When BP dropped to 50% of baseline rats received 1 of 7 treatments: (1) 0.9% saline (control), (2) levosimendan 36 μg/kg loading dose then 0.6 μg/kg per min, (3) levosimendan 0.6 μg/kg per min, (4) epinephrine 0.5 μg/kg per min, (5) levosimendan 70 μg/kg loading dose then 1.2 μg/kg per min, (6) levosimendan 1.2 μg/kg per min, and (7) levosimendan 70 μg/kg loading dose alone. Hemodynamics were recorded every 10 minutes for 70 minutes. Cardiac output, mean arterial pressure, and HR for each group were compared with control. Results: All groups had comparable baseline and maximal toxicity hemodynamics prior to initiation of treatment. Levosimendan did not improve CO or BP with any dosing regimen. Blood pressure tended to be lower than control for all doses of levosimendan. Epinephrine significantly improved BP but not CO compared to all other treatment groups. Survival did not differ between groups. Conclusions: Unlike in verapamil and metoprolol poisoning models, levosimendan did not improve CO or survival in propranolol poisoning. Epinephrine improved BP, but not CO, suggesting that its actions were due to peripheral vasoconstriction.