Objective To assess neurocognitive impairment after the off-pump and on-pump techniques for coronary artery bypass graft surgery in patients with triple vessel disease. Design Randomised controlled trial. Setting University Hospital of Wales, Cardiff. Participants 60 patients undergoing coronary artery bypass graft surgery for triple vessel disease prospectively randomised to the off-pump or on-pump technique. Main outcome measures Change in scores in nine standard neuropsychometric tests administered preoperatively and at 1 and 10 weeks postoperatively. Results The on-pump group showed a significantly greater deterioration in scores for two and three tests at 1 week and 10 weeks postoperatively, respectively, than the off-pump group. The on-pump group also showed a significantly higher incidence of major deterioration in one of the tests both 1 week and 10 weeks postoperatively. The incidence of neurocognitive impairment at 1 week postoperatively was 27% (8 out of 30) in the off-pump group and 63% (19 out of 30) in the on-pump group (P=0.004); and at 10 weeks postoperatively was 10% (3 out of 30) in the off-pump group and 40% (12 out of 30) in the on-pump group (P=0.017). Conclusion Off-pump coronary artery bypass graft surgery results in less neurocognitive impairment than the on-pump technique.
Abstract-Exposure of the neonatal lung to chronic hypoxia produces significant pulmonary vascular remodeling, right ventricular hypertrophy, and decreased lung alveolarization. Given recent data suggesting that stem cells could contribute to pulmonary vascular remodeling and right ventricular hypertrophy, we tested the hypothesis that blockade of SDF-1 (stromal cell-derived factor 1), a key stem cell mobilizer or its receptor, CXCR4 (CXC chemokine receptor 4), would attenuate and reverse hypoxia-induced cardiopulmonary remodeling in newborn mice. Neonatal mice exposed to normoxia or hypoxia were randomly assigned to receive daily intraperitoneal injections of normal saline, AMD3100, or anti-SDF-1 antibody from postnatal day 1 to 7 (preventive strategy) or postnatal day 7 to 14 (therapeutic strategy). As compared to normal saline, inhibition of the SDF-1/CXCR4 axis significantly improved lung alveolarization and decreased pulmonary hypertension, right ventricular hypertrophy, vascular remodeling, vascular cell proliferation, and lung or right ventricular stem cell expressions to near baseline values. We therefore conclude that the SDF-1/CXCR4 axis both prevents and reverses hypoxia-induced cardiopulmonary remodeling in neonatal mice, by decreasing progenitor cell recruitment to the pulmonary vasculature, as well as by decreasing pulmonary vascular cell proliferation. These data offer novel insights into the role of the SDF-1/CXCR4 axis in the pathogenesis of neonatal hypoxia-induced cardiopulmonary remodeling and have important therapeutic implications. Key Words: pulmonary hypertension Ⅲ hypoxia Ⅲ progenitor cells Ⅲ SDF-1 Ⅲ vascular remodeling D espite marked improvements in medical care, approximately 2 in 1000 neonates are perinatally exposed to intermittent or chronic periods of hypoxia. 1 Unlike that of the adult, the neonatal pulmonary vascular response to chronic hypoxic exposure is much more rapid and severe 2 and results in failure of the fetal circulation to adapt to a response that supports postnatal life. This in turn contributes to the pathogenesis of persistent pulmonary hypertension (PH) of the newborn, chronic lung disease of prematurity, and congenital heart disease. It is typically characterized by profound proliferation of smooth muscle and adventitial cells in the pulmonary vasculature and abnormal extension of smooth muscle into peripheral arteries, along with impairment in alveolar development in preterm neonates. 3,4 Although the mechanisms underlying neonatal hypoxiainduced cardiopulmonary remodeling remain unclear, recent studies have suggested that stem cells may contribute to systemic and pulmonary vascular remodeling. We therefore sought to examine the role of a key stem cell mobilizer, the chemokine SDF-1 (stromal cell-derived factor 1) and its receptor CXCR4 (CXC chemokine receptor 4) in neonatal chronic hypoxia-induced cardiopulmonary remodeling.SDF-1 or CXCL12 is a chemokine that is secreted by several tissues following exposure to hypoxia, 5,6 in turn leading to the release of p...
These data suggest that acute effects of MSC therapy in HILI are mainly paracrine mediated; however, optimum long-term improvement following HILI requires treatment with the MSCs themselves or potentially repetitive administration of CM.
BackgroundMesenchymal stem cells (MSC) improve alveolar and vascular structures in experimental models of bronchopulmonary dysplasia (BPD). Female MSC secrete more anti-inflammatory and pro-angiogenic factors as compared to male MSC. Whether the therapeutic efficacy of MSC in attenuating lung injury in an experimental model of BPD is influenced by the sex of the donor MSC or recipient is unknown. Here we tested the hypothesis that female MSC would have greater lung regenerative properties than male MSC in experimental BPD and this benefit would be more evident in males.ObjectiveTo determine whether intra-tracheal (IT) administration of female MSC to neonatal rats with experimental BPD has more beneficial reparative effects as compared to IT male MSC.MethodsNewborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 2- P21 were randomly assigned to receive male or female IT bone marrow (BM)-derived green fluorescent protein (GFP+) MSC (1 x 106 cells/50 μl), or Placebo on P7. Pulmonary hypertension (PH), vascular remodeling, alveolarization, and angiogenesis were assessed at P21. PH was determined by measuring right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling was evaluated by quantifying the percentage of muscularized peripheral pulmonary vessels. Alveolarization was evaluated by measuring mean linear intercept (MLI) and radial alveolar count (RAC). Angiogenesis was determined by measuring vascular density. Data are expressed as mean ± SD, and analyzed by ANOVA.ResultsThere were no significant differences in the RA groups. Exposure to hyperoxia resulted in a decrease in vascular density and RAC, with a significant increase in MLI, RVSP, and the percentage of partially and fully muscularized pulmonary arterioles. Administration of both male and female MSC significantly improved vascular density, alveolarization, RVSP, percent of muscularized vessels and alveolarization. Interestingly, the improvement in PH and vascular remodeling was more robust in the hyperoxic rodents who received MSC from female donors. In keeping with our hypothesis, male animals receiving female MSC, had a greater improvement in vascular remodeling. This was accompanied by a more significant decrease in lung pro-inflammatory markers and a larger increase in anti-inflammatory and pro-angiogenic markers in male rodents that received female MSC. There were no significant differences in MSC engraftment among groups.ConclusionsFemale BM-derived MSC have greater therapeutic efficacy than male MSC in reducing neonatal hyperoxia-induced lung inflammation and vascular remodeling. Furthermore, the beneficial effects of female MSC were more pronounced in male animals. Together, these findings suggest that female MSC maybe the most potent BM-derived MSC population for lung repair in severe BPD complicated by PH.
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