IGF-1 induces iNOS expression via the p38 MAPK signal pathway in the anti-apoptotic process in pulmonary artery smooth muscle cells during PAH.

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.

Application of extracorporeal cardiopulmonary resuscitation in adult patients with refractory cardiac arrest.

BACKGROUND: The aim of this study was to summarize the clinical experience of extracorporeal cardiopulmonary resuscitation (ECPR) in the treatment of adult patients with refractory cardiac arrest. METHODS: The clinical data of 12 cases of adult patients with cardiac arrest hospitalized between June 2015 and September 2019 who were unable to achieve return of spontaneous circulation effectively with conventional cardiopulmonary resuscitation (CCPR) and were treated with ECPR technology were retrospectively analyzed. The group included six males and six females aged between 18 and 69 years. All the patients underwent veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support with the adoption of femoral artery and vein catheterization. RESULTS: The duration of cardiopulmonary resuscitation (CPR) for the 12 patients was 32-125 min, and the ECMO duration was 2-190 h. Four patients were successfully weaned from ECMO and survived until hospital discharge. The other eight patients died in hospital; hemodynamic collapse (four patients) in the early stage of ECMO and severe neurological complications (three patients) were the main causes of death. CONCLUSIONS: Single-center data showed that ECPR provided a new rescue alternative for some patients with reversible refractory cardiac arrest. We have demonstrated that the success rate of treatment could be improved by selecting suitable patients and reducing the CPR duration as much as possible.

Lund exhaust on hemodynamic parameters and inflammatory mediators in patients undergoing cardiac valve replacement under cardiopulmonary bypass.

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.

[Muscle-sparing thoracotomy in chest surgery].

OBJECTIVE: To review the clinical experience of muscle-sparing thoracotomy in intrathoracic surgery. METHODS: Thoracotomy was performed in 386 patients from 1998 to 2002, during the procedure lateral-transverse incision, free dissection of muscular flap and entering to the thoracic cavity through certain intercostal space were applied. Two sets of rib retractors were used to ensure the excellent field exposure. RESULTS: Intrathoracic surgery was carried out by this method with the advantage of excellent surgical field exposure, less pain and relative quick recovery. CONCLUSION: Muscle-sparing thoracotomy has the merits of less injury and the same good exposure as routine thoracotomy and it can be carried out in majority of chest surgery.

Right axillary and femoral artery perfusion with mild hypothermia for aortic arch replacement.

OBJECTIVES: Aortic 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). METHODS: Between 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. RESULTS: The 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%). CONCLUSIONS: Aortic 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.