Hypertonic sodium lactate improves microcirculation, cardiac function, and inflammation in a rat model of sepsis
Emmanuel Besnier, David Coquerel, Geoffrey Kouadri, Thomas Clavier, Raphaël Favory, Thibault Duburcq, Olivier Lesur, Soumeya Bekri, Vincent Richard, Paul Mulder, Fabienne Tamion
Abstract
Abstract Background Hypertonic sodium lactate (HSL) may be of interest during inflammation. We aimed to evaluate its effects during experimental sepsis in rats (cecal ligation and puncture (CLP)). Methods Three groups were analyzed ( n = 10/group): sham, CLP-NaCl 0.9%, and CLP-HSL (2.5 mL/kg/h of fluids for 18 h after CLP). Mesenteric microcirculation, echocardiography, cytokines, and biochemical parameters were evaluated. Two additional experiments were performed for capillary leakage (Evans blue, n = 5/group) and cardiac hemodynamics ( n = 7/group). Results HSL improved mesenteric microcirculation (CLP-HSL 736 [407–879] vs. CLP-NaCl 241 [209–391] UI/pixel, p = 0.0006), cardiac output (0.34 [0.28–0.43] vs. 0.14 [0.10–0.18] mL/min/g, p < 0.0001), and left ventricular fractional shortening (55 [46–73] vs. 39 [33–52] %, p = 0.009). HSL also raised dP/dt max slope (6.3 [3.3–12.1] vs. 2.7 [2.0–3.9] 10 3 mmHg/s, p = 0.04), lowered left ventricular end-diastolic pressure-volume relation (1.9 [1.1–2.3] vs. 3.0 [2.2–3.7] RVU/mmHg, p = 0.005), and reduced Evans blue diffusion in the gut (37 [31–43] vs. 113 [63–142], p = 0.03), the lung (108 [82–174] vs. 273 [222–445], p = 0.006), and the liver (24 [14–37] vs. 70 [50–89] ng EB/mg, p = 0.04). Lactate and 3-hydroxybutyrate were higher in CLP-HSL (6.03 [3.08–10.30] vs. 3.19 [2.42–5.11] mmol/L, p = 0.04; 400 [174–626] vs. 189 [130–301] μmol/L, p = 0.03). Plasma cytokines were reduced in HSL (IL-1β, 172 [119–446] vs. 928 [245–1470] pg/mL, p = 0.004; TNFα, 17.9 [12.5–50.3] vs. 53.9 [30.8–85.6] pg/mL, p = 0.005; IL-10, 352 [267–912] vs. 905 [723–1243] pg/mL) as well as plasma VEGF-A (198 [185–250] vs. 261 [250–269] pg/mL, p = 0.009). Conclusions Hypertonic sodium lactate fluid protects against cardiac dysfunction, mesenteric microcirculation alteration, and capillary leakage during sepsis and simultaneously reduces inflammation and enhances ketone bodies.