Albumin replacement reduces mortality in hypoalbuminemic rats with LPS-induced endotoxemia

Abstract Background: Hypoalbuminemia may influence the clinical response and mortality induced by endotoxemia. Sepsis impairs adequate tissue perfusion, and early volume resuscitation by albumin or crystalloid administration is critical for clinical outcomes and survival. Methods: This study analyzed in hypoalbuminemic rats the effects of endotoxemia on vascular reactivity, cardiac function, oxidative and inflammatory profile, and survival. In addition, mortality was accessed after albumin replacement. Endotoxemia was induced in male Sprague Dawley (SD) or Nagase analbuminemic rats (NAR) using either lipopolysaccharide (LPS) injection or cecal ligation and puncture (CLP), with or without subsequent albumin replacement. Survival rates were assessed every 8 h for 5 days following LPS injection. Hemodynamic evaluations were conducted 4 hours post-LPS injection by measuring mean arterial pressure (MAP), left ventricular end-diastolic pressure, dP/dtmax, and dP/dtmin. Vascular reactivity of aortic rings was recorded 4 hours post-LPS. Oxidative stress, measured by thiobarbituric acid reactive substances (TBARS), and cytokine levels, determined by ELISA, were assessed at 1.5 and 4 hours post-LPS injection. Comparisons among groups were performed using ANOVA with post-hoc Tukey-Kramer analysis Results: Survival rates were lower in NAR+LPS (25%) and NAR+CLP (10%) compared to SD+LPS (80%) and SD+CLP (40%), but albumin replacement improved survival in NAR+LPS (25%) as compared to NAR+LPS+ALB (55%). Severe hemodynamic impairments, including reduced cardiac function and vascular reactivity, were observed in NAR+LPS. Baseline and post-LPS plasma levels of TBARS and nitric oxide were elevated in NAR, while TNF, IL-6, and IL-10 were higher in SD+LPS compared to NAR+LPS. Discussion: Subgroup analysis of studies with volume infusion suggests that septic patients with hypoalbuminemia may benefit from albumin infusion during shock. To further investigate the role of prior hypoalbuminemia in septic shock and the underlying pathophysiological mechanisms, we conducted a translational study bridging clinical findings with experimental research. The results demonstrate that hypoalbuminemia cause alterations in endothelial and vascular muscle function as well as cardiac dysfunction. Conclusion: Hypoalbuminemia in rats increase mortality from endotoxemia, associated with severe cardiovascular dysfunction and oxidative stress. Albumin replacement in hypoalbuminemic rats reduced mortality in endotoxemia-induced sepsis.