Ketamine ameliorates hypoxia-induced endothelial injury in human umbilical vein endothelial cells

OBJECTIVES: Hypoxia leads to endothelial cell inflammation, apoptosis, and damage, which plays an important role in the complications associated with ischemic cardiovascular disease. As an oxidoreductase, p66Shc plays an important role in the regulation of reactive oxygen species (ROS) production and apoptosis. Ketamine is widely used in clinics. This study was designed to assess the potential protective effect of ketamine against hypoxia-induced injury in human umbilical vein endothelial cells (HUVECs). Moreover, we explored the potential mechanism by which ketamine protected against hypoxia-induced endothelial injury. METHODS: The protective effects of ketamine against hypoxia-induced injury was assessed using cell viability and adhesion assays, quantitative polymerase chain reaction, and western blotting. RESULTS: Our data showed that hypoxia reduced HUVEC viability, increased the adhesion between HUVECs and monocytes, and upregulated the expression of endothelial adhesion molecules at the protein and mRNA levels. Moreover, hypoxia increased ROS accumulation and upregulated p66Shc expression. Furthermore, hypoxia downregulated sirt1 expression in HUVECs. Alternatively, ketamine was shown to reverse the hypoxia-mediated reduction of cell viability and increase in the adhesion between HUVECs and monocytes, ameliorate hypoxia-induced ROS accumulation, and suppress p66Shc expression. Moreover, EX527, a sirt1 inhibitor, reversed the protective effects of ketamine against the hypoxia-mediated reduction of cell viability and increase in adhesion between HUVECs and monocytes. CONCLUSION: Ketamine reduces hypoxia-induced p66Shc expression and attenuates ROS accumulation via upregulating sirt1 in HUVECs, thus attenuating hypoxia-induced endothelial cell inflammation and apoptosis.

Effect of intraoperative lung-protective mechanical ventilation on pulmonary oxygenation function and postoperative pulmonary complications after laparoscopic radical gastrectomy

This study aimed to observe the effects of lung-protective ventilation (LPV) on oxygenation index (OI) and postoperative pulmonary complications (PPCs) after laparoscopic radical gastrectomy in middle-aged and elderly patients. A total of 120 patients who were scheduled to undergo laparoscopic radical gastrectomy with an expected time of >3 h were randomly divided into conventional ventilation (CV group) with tidal volume (TV) of 10 mL/kg without positive end-expiratory pressure (PEEP), and lung-protective ventilation (PV group) with 7 mL/kg TV and personal level of PEEP with regular recruitment maneuver every 30 min. Measurements of OI, modified clinical pulmonary infection score (mCPIS), and PPCs were assessed during the perioperative period. Fifty-seven patients in the CV group and 58 in the PV group participated in the data analysis. Patients in the PV group showed better pulmonary dynamic compliance, OI, and peripheral capillary oxygen saturation during and after surgery. The mCPIS was significantly lower in the PV group than in the CV group after surgery. The incidence rate of PPCs was lower in the PV group than in the CV group and the difference was significant in patients whose ventilation time was longer than 6 h in both groups. LPV during laparoscopic radical gastrectomy significantly improved pulmonary oxygenation function and reduced postoperative mCPIS and the incidence of PPCs during the early period after surgery of middle-aged and elderly patients, especially patients whose mechanical ventilation time was longer than 6 h.