The Effects of Fluid Resuscitation on Renal and Cardiac Mitochondrial Function in a Severely Burned Swine Model

Severe burn injury covering over 30% of the total body surface area (TBSA) results in a systemic inflammatory response which can lead to multi organ dysfunction (MOD). Intravenous (IV) fluid resuscitation is a key component in the acute phase of burn treatment, however the volumes and types of fluids used (e.g., crystalloids vs. colloids) remain controversial. While previous studies have shown mitochondrial damage in organs such as heart and kidneys post‐burn, the effects of IV fluids on mitochondrial function have not been studied. The purpose of this study is to determine the effects of small volumes of crystalloid or colloid fluids on mitochondrial function following severe burns in a swine model. Anesthetized Yorkshire swine (n=14) sustained 40% TBSA full‐thickness contact burns with brass probes heated to 100°C placed in contact with the skin for 30 seconds. Animals were allowed to recover in metabolic cages and were given IV fluids (15 mL/kg/day) as either crystalloids (n=7) or colloids (n=7). Five non‐burned swine served as control. After 48 h, heart and kidney tissue were harvested and mitochondrial function was analyzed by high resolution respirometry. Substrates were added to determine the maximum oxidative phosphorylation (OXPHOS). Then the ATP synthase inhibitor, oligomycin was added to determine Leak respiration. Mitochondrial efficiency was defined as the coupling control ratio (OXPHOS/Leak). Citrate synthase (CS) assay was used for normalization of the data, and statistical significance was set at p<0.05. Mitochondrial abundance was significantly lower in swine kidney given colloid vs crystalloid (13.87 ± 2.35 vs 22.03 ± 1.68 nmol CS/ml/s, p<0.05, respectively) and control (23.77 ± 3.55 nmol CS/ml/s, p<0.05). Leak respiration per mitochondrion in heart tissues was significantly higher in burned swine given colloids than crystalloids (672.3 ± 82.74 vs 334.4 ± 50.27 pmol O 2 /mg/s/CS, p<0.01) and non‐burned controls (254.1 ± 57.77 pmol O 2 /mg/s/CS, p<0.01), indicating higher O 2 respiration without ATP synthesis. We found heart mitochondria in swine given colloids were significantly less efficient than controls (54% ± 6 vs 76% ± 5, p<0.05, respectively), which was not true after IV crystalloids (67% ± 7). This was also found in renal mitochondria where colloid (but not crystalloid‐treated) swine showed less ATP producing efficiency in the kidney than non‐burned controls (55% ± 6 vs 73% ± 5, p<0.05, respectively). For the first time, our study examined the effects of different IV fluids on mitochondrial function following severe burns. Our data suggest that resuscitation with crystalloids may be protective of mitochondrial abundance and function within the first 48 h following severe burns. Future studies to address timing and volume of resuscitation fluid administration are needed. Support or Funding Information This study was supported by Military Burn Research Program Award# W81XWH‐16‐2‐0041. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .