Sevoflurane inhibits cardiac function in pulmonary fibrosis mice through the TLR4 signaling pathway.

Abstract

Pulmonary fibrosis is often concomitant with myocardial injury. We studied sevoflurane’s effects on cardiac function and the expression of the TLR4/inducible nitric oxide synthase (iNOS) signaling pathway on a pulmonary fibrosis model. C57BL/6J wild-type (WT) and TLR4-deficient (TLR4−/−) mice were randomly divided into a control group and a pulmonary fibrosis group. The model of pulmonary fibrosis was induced by treatment with paraquat (PQ; 20 mg/kg). Four weeks after PQ administration, mice were tested for body weight changes, and histopathology and hydroxyproline in lung. Left ventricular function in each group of mice was measured by echocardiogram before and after sevoflurane inhalation. The expression of TLR4 and iNOS protein were analyzed. Pulmonary fibrosis mice were fed lenalidomide (50 mg/kg/day) for three days and cardiac function was assessed before and after sevoflurane inhalation. WT pulmonary fibrosis mice showed pathological damage and excessive deposition of collagen in the lung and heart. Left ventricular function decreased after four weeks of PQ exposure. TLR4−/− mice were resistant to pulmonary fibrosis like pathological damage and the effect of sevoflurane on heart rate and ejection fraction than that of WT mice. TLR4 and iNOS expression in WT pulmonary fibrosis mice increased significantly after sevoflurane inhalation. Lenalidomide treatment alleviated the effect of sevoflurane on heart rate and ejection fraction in WT pulmonary fibrosis mice. Sevoflurane inhibits cardiac function in pulmonary fibrosis mice through the TLR4/iNOS pathway. Lenalidomide attenuated the sevoflurane’s effect on the cardiac function of mice with pulmonary fibrosis.