The Nephroprotective Effect of Nitric Oxide during Extracorporeal Circulation: An Experimental Study.

This study aims to determine the effectiveness of administering 80 ppm nitric oxide in reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental perfusion. Twenty-four sheep were randomized into four groups: two groups received 80 ppm NO conditioning with 90 min of cardiopulmonary bypass (CPB + NO) or 90 min of CPB and hypothermic circulatory arrest (CPB + CA + NO), while two groups received sham protocols (CPB and CPB + CA). Kidney injury was assessed using laboratory (neutrophil gelatinase-associated lipocalin, an acute kidney injury biomarker) and morphological methods (morphometric histological changes in kidney biopsy specimens). A kidney biopsy was performed 60 min after weaning from mechanical perfusion. NO did not increase the concentrations of inhaled NO2 and methemoglobin significantly. The NO-conditioning groups showed less severe kidney injury and mitochondrial dysfunction, with statistical significance in the CPB + NO group and reduced tumor necrosis factor-α expression as a trigger of apoptosis and necroptosis in renal tissue in the CPB + CA + NO group compared to the CPB + CA group. The severity of mitochondrial dysfunction in renal tissue was insignificantly lower in the NO-conditioning groups. We conclude that NO administration is safe and effective at reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental CPB.

Two-stage approach for surgical treatment of tetralogy of Fallot in underweight children: Clinical and morphological outcomes.

BACKGROUND: Two-stage surgery including right ventricular outflow tract (RVOT) stenting with subsequent total surgical repair (TSG) has been suggested as a promising curative option in infants with tetralogy of Fallot (ToF) having comorbidities such as low body weight. However, data on clinical outcomes of such approach and tissue response to RVOT stenting in underweight infants are scarce. METHODS: We recruited 16 underweight (<3 kg; average weight, 2.2 ± 0.4 and 4.7 ± 0.9 kg at the time of RVOT stenting and TSG, respectively) infants (1-3 months of age, average 28.2 ± 4.3 and 100.2 ± 22.3 days at the time of RVOT stenting and TSG, respectively) with ToF and performed RVOT stenting with the subsequent TSG. Excised stents were embedded into epoxy resin and stained by toluidine blue and basic fuchsin. RESULTS: Fifteen infants had a favorable clinical outcome, probably due to the rapid increase in the body weight, blood oxygen saturation, and left ventricular end-diastolic volume to body surface area ratio indicative of improved pulmonary perfusion. Histological analysis revealed an endothelial cell monolayer at the stent surface with notable neovascularization of stented tissues, which could potentially explain the abovementioned clinical and echocardiography improvements. The only death occurred immediately after RVOT stenting and was caused by a massive subdural hematoma, possibly provoked by grade 2 intraventricular hemorrhage 12 days before the stenting. CONCLUSIONS: We confirm RVOT stenting with the subsequent TSG as a safe and efficient surgical approach for the treatment of underweight children with ToF.

Imbalance in the glutathione system in Opisthorchis felineus infected liver promotes hepatic fibrosis.

Although data on oxidative stress during liver fluke infection have been previously presented, a comprehensive study of the glutathione system that plays a crucial role in scavenging of reactive oxygen species (ROS) and detoxification of primary and secondary oxidation products has not been addressed yet. In the present study, the hepatic glutathione system was investigated in a hamster model of experimental opisthorchiasis infection. It was shown that chronic oxidative stress in an Opisthorchis felineus infected liver, evidenced by abundant hydroperoxide accumulation, leads to strong imbalance in the hepatic glutathione system, namely the depletion of reduced form of glutathione (GSH), lowering of the GSH/GSSG ratio, and a decrease in the glutathione peroxidase and glyoxalase 1 activity. O. felineus infection provokes hepatocellular damage that results in the progression of liver fibrosis, accompanied by an increase in collagen deposition in the hepatic tissue. Modulation of hepatic GSH levels in the O. felineus infected liver through N-acetylcysteine (NAC) or l-buthionine-S, R-sulfoxinine (BSO) treatments lead to changes in expression and activity of glutathione S-transferase and glyoxalase I as well as markedly decreases or increases collagen content in the O. felineus infected liver and the severity of liver fibrosis, respectively. Thus, the glutathione system can be considered as a target for liver protection from O. felineus-induced injury.