Protective Effects Of Combined Levosimendan And Vasopressin On Pulmonary Function In Porcine Septic Shock

Purpose: To investigate the effects of combined levosimendan and vasopressin on hemodynamics and pulmonary function in porcine septic shock.Method: Fecal peritonitis was induced in32anesthetized, invasively monitored, mechanically ventilated female swine. Following the time point of septic shock (defined as mean artery pressure<60mmHg), swine were randomly assigned to the following groups (each, n=8):(1) norepinephrine (NE group);(2) levosimendan (0.4g>kg-1>min-1)+norepinephrine (LEVO+NE group);(3) arginine vasopressin (0.57mU>kg-1>min-1)+norepinephrine (AVP+NE group);(4) levosimendan (0.4g>kg>min-1)+arginine vasopressin (0.57mU>kg-1>min-1)+norepinephrine (LEVO+AVP+NE group). If necessary, norepinephrine was titrated to maintain mean artery pressure (MAP) between65and75mmHg in the LEVO+NE, AVP+NE group, and LEVO+AVP+NE groups. Heart rate (HR), MAP, mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central ven(pressure (CVP), infusion volume, and blood gas analysis were evaluated at the following ti points: baseline (T1), shock time (T2),4(T3),8(T4) and12h (T5) after septic shock. Norepinephrine requirements were recorded every30-minutes-period after the onset of septic shock. Venous admixture (Qs/Qt), systematic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated by standard formula. Arterial and mixed venous blood samples were simultaneously obtained for immediate determination of arterial and mixed venous oxygen saturations, partial pressure of oxygen (PaO2). Arterial blood samples were obtained for determination of hematocrit (Hct), pH, lactate concentrations, TNF-, IL-6, high mobility group box1, IL-10, and NOx. Lung was removed for determination of TNF-, IL-6, high mobility group box1, IL-10, NOx, W/D, MPO, histological changes and TUNEL staining.Results: MAP, Hct, CVP, PCWP, pHa, and fluid requirements were similar among the four groups (P>0.05). CO in LEVO+AVP+NE group was significantly higher at T4and T5when compared with AVP+NE group (P<0.05). MPAP, serum IL-6, lactate concentrations, NOx, HMGB1, and Qs/Qt were significantly lower in LEVO+AVP+NE group at T5than those in NE group (P<0.05). There were significantly lower IL-6, W/D, total histological scores, apoptotic cells, and when compared with NE group (P<0.05).Conclusions: LEVO combined with AVP infusion improves sepsis-induced acute lung injury by improving hemodynamics, and attenuating inflammatory responses and apoptosis in the lung comparing to NE infusion alone.