Levosimendan pretreatment improves systemic hemodynamics and metabolism during acute hypoxia in dogs

Background & Goal of Study: 
Levosimendan (LEVO) improves regional tissue oxygenation under physiological, normoxic conditions, as we demonstrated recently [1]. It is unclear, however, if LEVO exerts beneficial effects also under pathological, hypoxic conditions, particularly in respect to systemic hemodynamics and metabolism. Thus we studied the effects of LEVO pretreatment during acute hypoxia on systemic hemodynamics and metabolism.

Materials & Methods: 
Chronically instrumented dogs (bodyweight ~30 kg,n 10 experiments) were anesthetized (sevoflurane, 1.5 MAC) and mechanically ventilated (FiO₂ 0.3; etCO₂ 35 mmHg). The animals were randomized to undergo hypoxia (FiO₂ 0.1 for 15 min) with or without LEVO pretreatment [1]. To assess systemic hemodynamics we measured cardiac output (CO), stroke volume (SV) and the inotropy marker dP/dTmax. To assess systemic metabolism, we measured O₂-consumption (VO₂, DeltatracII) and arterial lactate levels. Data are mean ± SEM. 

Results & Discussions:
Hypoxia (FiO₂ 0.1) reduced arterial PO₂ from ~130 mmHg to ~30 mmHg in both groups, i.e., hypoxia with and without LEVO pretreatment. LEVO pretreatment significantly improved systemic hemodynamics during hypoxia, i.e., CO (104 ± 4 vs 83 ± 5 ml/kg/min), SV (25.2 ± 1. 7 vs 19.8 ± 1.2 ml) and dP/dT max (553 ± 41 vs 377 ± 36 mmHg/sec). These hemodynamic improvements were not fueled by increased O₂-consumption, i.e., VO₂ did not differ between groups (3.1 ± 0.2 vs 3.0 ± 0.2 ml/kg/min). Interestingly, LEVO pretreatment prevented an increase in arterial lactate during hypoxia (1.8 ± 0.1 to 1.9 ± 0.1 mmol/L), whereas lactate significantly increased in the group without LEVO (1.7 ± 0.1 to 2.1 ± 0.1 mmol/L).

Conclusion(s): 
LEVO pretreatment markedly improved systemic hemodynamics during acute hypoxia, without increasing oxygen consumption. Furthermore, LEVO pre-treatment prevented the increase in arterial lactate levels during acute hypoxia, indicating an optimized O₂-distribution and/or utilization by LEVO. Thus, if our data apply to the clinical setting, LEVO pretreatment is a promising option to improve systemic hemodynamics without increasing VO₂ and furthermore to optimize lactate balance in patients atrisk of hypoxia.

Reference:
[1] Schwarte LA et al. Crit Care Med. 2005; 33: 135–142