Systemic and regional effects of levosimendan and arginine–vaopressine in endotoxin-treated rabbits

Vascular and myocardial dysfunctions are often combined in septic mammals. Septic shock treatment therefore usually associates vasoconstricting and positive inotropic agents, mostly dopamine, norepinephrine (NE) and/or dobutamine. An alternative can be the use of noncatecholamine agents: arginine–vaopressine (AVP) and levosimendan (LS).

Methods

Thirty-six hours after intravenous endotoxin (LPS) administration, 26 rabbits were anaesthetised and ventilated. Systolic arterial pressure (sAP), diastolic arterial pressure (dAP), and mean arterial pressure (mAP) (mmHg), systolic aortic blood flow velocities (sAoV) and mean aortic blood flow velocities (mAoV) (20 MHz pulsed Doppler; cm/s), and systolic renal artery blood flow (sRen) and diastolic renal artery blood flow (dRen) (transonic Doppler, ml/min) were measured in anaesthetised and ventilated rabbits. Heart inotropic quality was estimated by maximal acceleration (Gmax, cm/s²) and sAoV. After 30 min stabilisation, rabbits received levosimendan (200 μg/kg/hour, LS+) or saline (LS-) for 30 min. They were then separated into four groups: (1) LS+ with NE (1 μg/kg/min, 90 min); (2) LS+ with AVP (14 ng/kg/min, 90 min); (3) NE alone; (4) AVP alone. All parameters were gaussian. Statistical analysis was performed using one-way and two-way ANOVA.

Results

LS consistently improved sAoV and Gmax within 30 min (P < 0.05 for both), while sAP, dAP, and mAP decreased (P < 0.05). Addition of AVP or NE similarly restored mean arterial pressure. However, their effects on myocardial function diverged. While NE did not alter sAoV and Gmax, AVP dramatically deteriorated both contractile parameters (-25% and -45%, respectively, after 60 min; both P < 0.01). This effect of AVP was observed when used in combination with LS or alone. No significant effect of treatments was observed on sRen and dRen.

Summary

Our study demonstrated that LS is a good alternative to restore cardiac contractile function when combined with NE. The use of AVP may lead to further deteriorate sepsis-related myocardial dysfunction even when combined with a positive inotropic agent.