The effect of nitric oxide donation on the severity of mitochondrial disfunction to the renal tissue in cardiopulmonary bypass simulation: an experimental study

Abstract

INTRODUCTION: Acute kidney injury is one of the common complications in cardiosurgical operations with cardiopulmonary bypass (CPB). A number of studies have shown that donation of exogenous nitric oxide (NO) reduces episodes of аcute kidney injury. However, subcellular mechanisms of realization the nephroprotective properties of NO remain unknown. OBJECTIVE: To study the safety of the technology of plasma-chemical synthesis of nitric oxide and to evaluate the effect of the delivery resulting nitric oxide on mitochondrial damage to the renal tissue in the simulation of cardiopulmonary bypass. MATERIALS AND METHODS: Experiment included 12 rams of the Altai breed. Animals were divided into 2 groups: 6 animals were modeled CPB; 6 animals were simulated CPB with NO delivery. Mitochondrial damage was assessed by calcium-binding capacity and transmembrane potential of mitochondria 1 h after weaning from the CPB. The safety of the NO delivery according to the proposed method was assessed by the concentration of nitrogen dioxide on inspiration, the level of methemoglobin. The efficiency of NO delivery according to the proposed method was assessed by the level of stable NO metabolites: endogenous nitrite, nitrate and total concentration of NO metabolites. RESULTS: In the group of animals with NO delivery the average level of transmembrane potential of mitochondria was (171.66 ± 20.41 vs 126.66 ± 18.61; p = 0.00256) and calcium-binding capacity of mitochondria was (1466.66 ± 216.02 vs 866.66 ± 216.02; p = 0.000712) of renal parenchyma. Methemoglobin levels above the recommended thresholds in clinical practice were not recorded in the CPB+NO group. The values of total concentration of NO metabolites and nitrate in the CPB+NO group compared to the CPB group are statistically significantly higher, p = 0.00006; p = 0.0035, respectively. CONCLUSIONS: Plasma-chemical synthesis of nitric oxide is a safe technology, and the use of the resulting nitric oxide in cardiopulmonary bypass leads to a decrease in the severity of mitochondrial dysfunction in the kidney parenchyma.