Background:
Ca2+-sensitiser levosimendan became first-line treatment in acute systolic dysfunction. We aimed to evaluate haemodynamic and arrhythmogenic effects of levosimendan (LEV) administered together with catecholamines (dobutamine, DOB; dopamine, DA; norepinephrine, NE) in a canine heart failure (HF) model.

Material and Methods:
HF (n=12) was induced by chronic right ventricular tachy-pacing. Two groups of anesthetized animals were constituted: Group I. - continuous infusion of LEV (0.1 g/kg/min iv.) with 10-10 minutes infusions of CAs: DOB3-6-12, DA4-8-16 és NE0,04-0,08-0,16 (μg/kg/min, iv.); Group II. – CAs were given in same doses without LEV. Measured, calculated variables: blood pressure (BP), left ventricular end-diastolic pressure (LVEDP), contractility (dP/dtmin-max), duration of monophasic action potential at 50%, 90% of repolarisation (MAPD50, MAPD90).

Result:
In Group I. LEV alone did not alter mean BP (105±13 mmHg), LVEDP (28±5 mmHg). dP/dtmax, dP/dtmin were increased by 56±15, 49±15 delta % (p<0,001). There was further increase in dP/dtmax with LEVO+CAs. In Group II. basal haemodynamics (BP, LVEDP, dP/dtmax, dP/dtmin) did not differ significantly from Group I. Moreover, CAs without LEV exerted cardiovascular responses similar to those in LEV+CA group. Malignant ventricular arrhythmias were not observed in both groups. During LEV infusion MAPD50 decreased significantly (214±8 vs 242±9 msec, p<0,01), which was further shortened by LEV+NA0,16 (204±20 msec, p<0,02).

Conclusion:
Co-administration of levosimendan and catecholamines elicited similar improvement in cardiac contractility to catecholamines given separately. This beneficial effect was not accompanied by malignant arrhythmias.
Granted by OTKA 10555