Hemodynamic effects of levosimendan after surgery in LPS pretreated rabbits

Introduction

Sepsis induces myocardial dysfunction and vascular hypocontractility. Recent data suggest that phosphorylation of myocardial contractile proteins decreases myofilament sensitivity to calcium and may contribute to myocardial depression [1]. Levosimendan (LS), a new calcium sensitizing drug and K_ATP channel opener, is used in human heart failure [2].

Aim

To evaluate the LS effect on heart function, vascular tone and renal microcirculation in rabbit without LPS (LPS-) and 36 hours after LPS administration (LPS+).

Methods

n = 8 LPS+ and n = 4 LPS- rabbits were analyzed. No animal died following LPS or saline injection, nor during the experiment. Heart rate (HR), systolic (sAP) and diastolic (dAP) arterial pressure (mmHg), systolic (sAoV), and mean aortic (mAoV) blood flow velocities (20 MHz pulsed Doppler [cm/s]), systolic (sRen) and diastolic (dRen) renal artery blood flow (transonic Doppler [ml/min]) and renal cortical (Cort) and medullary (Med) flows (laser Doppler [tissue perfusion units, TPU]) were measured in anesthetized and ventilated rabbits. Heart inotropic quality was estimated by maximal acceleration (γ max [cm/s]) and sAoV. In the LPS+ group, LPS (600 μg/kg) was injected 36 hours before the experiment. Data were collected in both groups before and at the end of a fluid loading test (20 ml in 5 min), 10 min after, and then every 15 min during a 4 hour LS infusion (200 μg/kg per hour).

Statistical analysis was performed using one-way and two-way ANOVA.

Results

(Mean ± SD, all parameters were gaussian.) Myocardial failure in LPS+ animals was confirmed by fluid loading effect on γ max and sAoV (+8% vs +14% and +8% vs +20%, respectively, in LPS+ and LPS-; P < 0.05, two-way ANOVA).

Despite its effects on macrocirculation, LS only slightly decreased Cort in LPS- animals, whereas no effect was observed on Med (Table 1).

Table 1 Effects of LS

Conclusion

In this model of endotoxin-induced myocardial dysfunction, LS improved cardiac systolic parameters. Hypotension could be related to LS interaction with K_ATP channels. The effects on renal macro and microcirculation need further investigation.