Hydrogen sulfide induces apoptosis of pulmonary artery smooth muscle cell in rats with pulmonary hypertension induced by high pulmonary blood flow

Background Abnormal apoptosis of pulmonary artery smooth muscle cells （PASMCs） is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide （H2S） on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow. Methods Thirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt＋propargylglycine （PPG）, 11-week control, 11-week shunt and 11-week shunt＋sodium hydrosulfide （NariS） groups. Rats in 4-week shunt, 4-week shunt＋PPG, 11-week shunt and 11-week shunt＋NariS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt＋PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H2S production, for 4 weeks. Rats in 11-week shunt＋NariS group were intraperitoneally injected with NariS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling （TUNEL）. Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining. Results Four weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased （P 〈0.01）, but expression of bcl-2 increased significantly （P 〈0.01）. PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 （P 〈0.01）, but increased the expression of bcl-2 （P 〈0.01）. After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased （P 〈0.01）, but expression of bcl-2 increased obviously （P 〈0.01）. NariS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2. Conclusions H2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.

Natural History of Kawashima Palliation in Single-Ventricle and Interrupted Inferior Vena Cava Heart Disease in China 11 Years Result

Background:The long-term outcomes of patients treated with a Kawashima procedure and keeping the antegrade pulmonary blood flow(AnPBF)in single-ventricle(SV)and interrupted inferior vena cava(IVC)heart disease is still uncertain as yet.Methods:We investigated 18 patients who underwent the Kawashima procedure with SV physiology and an interrupted IVC between January 2009 and June 2018,perioperative,operative and postoperative characteristics were recorded.Results:A total of 18 patients underwent the Kawashima procedure at a median age of 2.7 years(range 0.5–24.7 years),of which 12(66.7%)were male and 6(33.3%)were female.The mean saturation was 76.2±8.5%in preoperative period and 94.2±2.2%in postoperative period.All patients had kept AnPBF.The median duration of mechanical ventilation was 12 h(range 2.5–22.5 h)and the median duration of pleural drainage was 5 days(range 2–27 days).The median hospital stay was 9 days(range 6–70 days).There was no operative death and no mortality was seen in early postoperative period.Follow-up was 100%completed,with an average follow-up period of 6.1±2.7 years(range 1–11 years).4 patients died during the follow-up.The overall 5 and 10 years’survival rates estimated by Kaplan-Meier method were 88%and 68%,respectively.Although there were no significant differences in the duration of postoperative follow-up between the death group and the survival group(p>0.05),the major systemic ventricular end-diastolic diameter(SVEDD)(p=0.018)and the degree of AVVR(p=0.001)showed significant difference between the two groups.The diameters of main pulmonary artery showed significant growth in both the death group(p=0.015)and the survival group(p=0.012)over time.SVEDD had no significant increase in the survival group(p=0.665)but was significantly larger in the death group(p=0.014).Multivariable risk factors of late mortality in patients treated with Kawashima procedure were follow-up AVVR(p=0.044;HR:3.124;95%CI:1.030–9.473)and SVEDD(p=0.031;HR:9.766;95%CI:1.226–77.8).14 patients(100%)were all in New York Heart Association(NYHA)functional class I and the mean saturation was 93±2%at last follow-up.Only one patient finished Fontan completion.Conclusions:The Kawashima procedure with AnPBF can be safely performed with acceptable early and long outcomes.Although some previous studies have shown the risk of pulmonary arteriovenous malformations(PAVMS)after Kawashima procedure in the mid-and long-term,our findings are in contradiction with it.No PAVMs occurred in all the survivors.Kawashima procedure with open AnPBF may be a good option for unsuitable Fontan candidates.