Abstract

Background: In patients admitted to the Intensive Care Unit (ICU), mortality is high due to multiple organ damage. Mitochondrial dysfunction and impaired oxygen consumption, as causative mechanisms, play a significant role in reducing the activity of immune cells in sepsis, resulting in the progression of the multiple organ dysfunction syndromes (MODS). The evaluation of mitochondrial function in critical care patients in the immune cells, especially in lymphocytes, could reveal the target point that determines mitochondrial failure.

Objective: To find the relationship between mitochondrial reactive oxygen species production (mROS), mitochondrial membrane potential (ΔΨm), and mitochondrial oxygen consumption (mVO₂) in peripheral plasma lymphocytes collected from ICU patients. We also compared these three characteristic mitochondrial functions with C-reactive protein (CRP), serum lactate, and central venous saturation (SvO₂) that would enable the prediction of the ultimate outcome.

Methods: Isolated lymphocytes from 54 critical care patients with SIRS by sepsis and non-sepsis etiologies were analyzed with flow cytometry by staining with dihydroethidium and JC-1, measuring mROS, ΔΨm, and mVO₂. Clinical variables, such as serum lactate (mmol/L) and C-reactive protein (mg/L) from peripheral blood, were measured in the first 24 hours of admission. A confounding analysis was performed using logistic regression, and a p-value of <0.05 was considered statistically significant.

Results: It has been confirmed that there is a drastic increase in reactive oxygen species (ROS) and mVO2 in critically ill patients immediately after exposure to the insult pathogen-associated molecular pattern /damageassociated molecular pattern (PAMPS/DAMPS) and continued for the first 24 hours thereafter. The results showed no significant alterations in the mitochondrial membrane potential (ΔΨm) compared with the lymphocytes in controls. A significant correlation between CRP and SvO₂ and a strong positive relationship between CRP, values above 3 mg/l, and white blood cells were observed.

Conclusion: Lymphocytes from patients with SIRS displayed higher mitochondrial respiratory capacities and reactive oxygen species production compared with controls. Clinical markers of inflammation indirectly evaluate the mitochondrial function, most of which have been validated in a clinical setting.

Keywords: Mitochondrial dysfunction, oxidative stress, sepsis, ICU, SIRS, CRP.