Sepsis causes profound circulatory dysfunction that includes global hemodynamic changes and critical impairment of the microcirculation. Prior experimental work has shown that hypertonic sodium lactate (HSL) can improve hemodynamics, modulate inflammation, and support cellular metabolism in sepsis models. However, microcirculatory effects—the perfusion of small vascular beds that determine tissue oxygen delivery—had not been specifically addressed. This study evaluated the effects of HSL on microcirculatory function in vivo in a resuscitated rat model of cecal ligation and puncture (CLP) and explored direct effects of lactate on vascular reactivity ex vivo.
The investigators used a resuscitated CLP model in male Wistar rats to mimic polymicrobial sepsis. Ten hours after CLP, animals were infused for 18 hours with either standard isotonic crystalloid (0.9% NaCl) or 11.2% hypertonic sodium lactate (HSL) prior to physiologic and microcirculatory exploration. The report summarizes systemic hemodynamic monitoring (arterial pressure, echocardiography, pressure–volume loops) and assessment of mesenteric perfusion and plasma inflammatory markers. Specific procedural details beyond timing, fluid concentrations, and duration were not reported in the abstract.
Systemic macrocirculatory variables including arterial pressure, echocardiographic parameters, and pressure–volume loop measurements did not differ between HSL-treated and control groups, indicating no detectable change in global arterial pressure or cardiac performance in this model under the conditions tested.
By contrast, mesenteric microvascular perfusion was improved in HSL-treated septic rats. Reported perfusion measurements showed higher mesenteric perfusion in the HSL group with median values of 1126 (interquartile range 923–1300) Perfusion Units versus 816.5 (692–919) Perfusion Units in the 0.9% NaCl group (p = 0.012). This indicates a statistically significant enhancement of regional microcirculatory blood flow with HSL despite the absence of macrohemodynamic differences.
Systemic inflammation was assessed by plasma tumor necrosis factor-alpha (TNF-α). TNF-α concentrations were lower in the HSL group: median 26.2 (22.8–37.1) pg/mL compared with 42.6 (32.6–47.3) pg/mL in controls (p = 0.001). The authors interpret this as an anti-inflammatory effect associated with HSL infusion in septic animals.
To determine whether lactate exerts direct vascular effects, the investigators performed ex vivo reactivity experiments on mesenteric small arteries from healthy rats. Vessels were tested under conditions that included LPS stimulation to mimic inflammatory impairment and glucose deprivation to challenge metabolic substrate availability.
Lactate restored vasoconstrictive responses that had been impaired by LPS in a dose-dependent manner, demonstrating a direct effect of lactate on small artery function independent of systemic influences. Under glucose deprivation, HSL was also able to restore vascular reactivity in both unstimulated and LPS-stimulated arteries, suggesting that lactate can serve as an alternative fuel supporting vascular smooth muscle contractile function when glucose is scarce.
The ex vivo findings therefore provide mechanistic support for the in vivo improvement in mesenteric perfusion and indicate that lactate interacts directly with the vasculature to preserve or restore responsiveness.
Together, the in vivo and ex vivo data indicate that HSL infusion in this resuscitated CLP rat model specifically improved microcirculatory perfusion and reduced systemic inflammatory marker levels without altering measured global arterial pressure or cardiac indices. The ex vivo experiments support a direct vascular action of lactate, including a role as an alternative metabolic substrate during glucose deprivation.
The authors conclude these benefits support the translational potential of HSL as a resuscitation fluid in sepsis. The study emphasizes the importance of assessing microcirculatory endpoints separately from macrohemodynamics when evaluating adjunctive resuscitation strategies.
The study reported ethics approvals from the relevant animal research ethics committee (CENOMEXA no. 54) with approval numbers cited. The authors declared no competing interests related to the present subject. The abstract reports primary outcomes and key numerical results but does not provide full methodological detail, sample sizes, survival data, or additional inflammatory mediators in the abstract; those details are not reported in the provided source text and would require consultation of the full article for complete appraisal.