Apoptosis and cell proliferation are two important cellular processes that determine the accumulation of pulmonary artery smooth muscle cells (PASMC) during pulmonary arterial hypertension (PAH). Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, also tissue repair. Inducible nitric oxide synthase (iNOS) has been shown to serve many vasoprotective roles in vascular smooth muscle cells (VSMCs) including inhibition of VSMC proliferation and migration and stimulation of endothelial cell growth. In this study, we investigated the involvement of iNOS in the process of IGF-1-induced inhibition of PASMC apoptosis. We also examined the role of p38 mitogen-activated protein kinase (MAPK) in the IGF-1-induced iNOS activation. Our results show that exogenous IGF-1 induced the up-regulation of iNOS in PASMC. Immunofluorescence of IGF-1 and iNOS showed a decreased immunostaining of both IGF-1 and iNOS in the cytoplasm and the perinucleus under serum deprivation condition. iNOS inhibition in PASMC in vitro markedly induced IGF-1-mediated anti-apoptosis as assessed by the cell viability measurement, Western blot, mitochondrial potential analysis and nuclear morphology determination. A p38 MAPK inhibitor blocked all the effects of IGF-1 on iNOS. Our findings suggest that IGF-1 inhibits cells apoptosis in PASMC by activating the p38 MAPK-iNOS transduction pathway. This mechanism may contribute to the accumulation of PASMC in early human PAH.

ObjectivesAortic arch replacement is associated with increased mortality and morbidity especially in acute type-A aortic dissection. Although hypothermic circulatory arrest with selective antegrade cerebral perfusion has been widely used because of its excellent cerebral protection, its optimal perfusion characteristics are unknown. The present study investigates clinical results obtained after perfusion method modification and temperature management during cardiopulmonary bypass (CPB).MethodsBetween July 2010 and August 2012, 16 consecutive adult patients (mean age 50.0 yr ± 14.1 yr, range 25 yr to 73 yr, 12 males, 4 females) who presented with acute Stanford type-A aortic dissection underwent aortic arch replacement (total arch, n = 11; hemiarch, n = 5) under mild hypothermia (31.1°C ± 1.5°C) with right axillary and femoral artery perfusion.ResultsThe mean CPB time was 201 min ± 53 min, and the mean myocardial ischemic time was 140 min ± 42 min. The mean selective cerebral perfusion time was 80 min ± 16 min, and the mean lower-body circulatory arrest time was 20 min ± 13 min. No patient death occurred within 30 post-operative days. The following details were observed: new post-operative permanent neurologic deficit in 1 patient (6.3%), temporary neurologic deficit in 2 patients (12.5%), acute renal dysfunction (creatinine level > 230 umol/L) in 3 patients (18.8%) and mechanical ventilation > 72 h in 5 patients (31.2%).ConclusionsAortic arch replacement for acute type-A aortic dissection under mild hypothermia with right axillary and femoral artery perfusion could be safely performed in the patient cohort.

The effect of Lund exhaust technique on hemodynamics and inflammatory mediators in patients undergoing cardiac valve replacement under cardiopulmonary bypass was evaluated. A total of 60 patients with heart disease undergoing elective heart valve replacement under elective cardiopulmonary bypass were randomly divided into Lund exhaust group (group A) and control group (group B), with 30 patients in each group. Group A underwent Lund exhaust during cardiopulmonary bypass, while group B was identical to group A except for not using the Lund exhaust technique during cardiopulmonary bypass. The hemodynamic parameters at different time-points showed that the indexes of MAP, PASP, CO, CI, PCWP, CVP and SVR in T1, T2, T3 and T4 moments between group A and group B were statistically significant (p<0.05). There was no statistical significance in IL-6, IL-8, IL-10, TNF-α and TIMP-1 between group A and group B patients at the T0 moment (p>0.05). The levels of IL-6, IL-8, IL-10, TNF-α and TIMP-1 in group B patients at T1, T2, T3 and T4 moments were statistically significant compared with those in group A (p<0.05). The IL-6, IL-8, TNF-α indexes of group B patients were statistically significant at the T5 moment compared with those in group A (p<0.05). The IL-10 and TIMP-1 of two groups were not statistically significant at the T5 moment. The operating time, CPB time, aortic clamp time, intraoperative blood loss, postoperative tube time, ICU stay time, hospital stay time and pulmonary infection of patients in group A were significantly less than those in group B. In conclusion, Lund exhaust technology can significantly reduce the fluctuation of hemodynamics, decrease the expression of inflammatory factors, improve lung function, and is conducive to the rehabilitation of patients.