Hemodynamic monitoring and optimization improve postoperative outcome during high-risk surgery. However, hemodynamic management practices among Chinese anesthesiologists are largely unknown. This study sought to evaluate the current intraoperative hemodynamic management practices for high-risk surgery patients in China. From September 2010 to November 2011, we surveyed anesthesiologists working in the operating rooms of 265 hospitals representing 28 Chinese provinces. All questionnaires were distributed to department chairs of anesthesiology or practicing anesthesiologists. Once completed, the 29-item questionnaires were collected and analyzed. Two hundred and 10 questionnaires from 265 hospitals in China were collected. We found that 91.4% of anesthesiologists monitored invasive arterial pressure, 82.9% monitored central venous pressure (CVP), 13.3% monitored cardiac output (CO), 10.5% monitored mixed venous saturation, and less than 2% monitored pulse pressure variation (PPV) or systolic pressure variation (SPV) during high-risk surgery. The majority (88%) of anesthesiologists relied on clinical experience as an indicator for volume expansion and more than 80% relied on blood pressure, CVP and urine output. Anesthesiologists in China do not own enough attention on hemodynamic parameters such as PPV, SPV and CO during fluid management in high-risk surgical patients. The lack of CO monitoring may be attributed largely to the limited access to technologies, the cost of the devices and the lack of education on how to use them. There is a need for improving access to these technologies as well as an opportunity to create guidelines and education for hemodynamic optimization in China.

Ischemia/reperfusion (I/R) injury of the lung can lead to extensive pulmonary damage. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are insulin-independent, oral antihyperglycemic agents used for treating type 2 diabetes mellitus (T2DM). Although their cardioprotective properties have been reported, their potential roles in pulmonary protection in vivo are poorly characterized. Here, we tested a hypothesis that empagliflozin, an SGLT2 inhibitor, can protect lungs in a mouse model of lung I/R injury induced by pulmonary hilum ligation in vivo. We assigned C57/BL6 mice to sham-operated, nonempagliflozin-treated control, or empagliflozin-treated groups. Pulmonary I/R injury was induced by 1-hour left hilum ligation followed by 2-hour reperfusion. Using quantitative polymerase chain reaction (q-PCR) and Western blot analysis, we demonstrate that SGLT2 is highly expressed in mouse kidney but is weakly expressed in mouse lung (n = 5-6 per group, P < 0.01 or P < 0.001). Empagliflozin improved respiratory function, attenuated I/R-induced lung edema, lessened structural damage, inhibited apoptosis, and reduced inflammatory cytokine production and protein concentration in bronchoalveolar lavage (BAL) fluid [P < 0.05 or P < 0.001 versus control group (CON)]. In addition, empagliflozin enhanced phosphorylation of pulmonary extracellular signal-regulated kinases 1 and 2 (ERK1/2) post-I/R injury in vivo (P < 0.001, versus CON, n = 5 per group). We further showed that pharmacological inhibition of ERK1/2 activity reversed these beneficial effects of empagliflozin. In conclusion, we showed that empagliflozin exerts strong lung protective effects against pulmonary I/R injury in vivo, at least in part via the ERK1/2-mediated signaling pathway. SIGNIFICANCE STATEMENT: Pulmonary ischemia-reperfusion (I/R) can exacerbate lung injury. Empagliflozin is a new antidiabetic agent for type 2 diabetes mellitus. This study shows that empagliflozin attenuates lung damage after pulmonary I/R injury in vivo. This protective phenomenon was mediated at least in part via the extracellular signal-regulated kinases 1 and 2-mediated signaling pathway. This opens a new avenue of research for sodium-glucose cotransporter-2 inhibitors in the treatment of reperfusion-induced acute pulmonary injury.

Renal ischemia/reperfusion (I/R) can induce acute kidney injury. Empagliflozin is a newly developed inhibitor of sodium-glucose cotransporter-2 (SGLT2) approved as an antidiabetic medication for patients with type 2 diabetes mellitus. Despite the established cardioprotective functions of empagliflozin, its protective role in renal I/R is unclear. Here, the present study evaluated the renoprotective effects of empagliflozin in a mouse model of renal I/R injury. Male C57/BL6 mice were allocated to sham-operated, I/R, and empagliflozin groups. Kidney pedicles on both sides were clamped for 45 min and were reperfused for 24 h. Empagliflozin (1 mg/kg) was administered to the mice for 2 days preischemia. The GSK-3β inhibitor SB216763 was administered intravenously at the beginning of reperfusion (0.1 mg/kg). Renal function and histological scores were evaluated. The kidneys were taken for immunohistochemical analysis, western blotting and apoptosis measurements. We found that empagliflozin decreased serum levels of creatinine and urea, reduced the average kidney weight-to-tibia length ratio, attenuated tubular damage, reduced renal proinflammatory cytokine expression and inhibited apoptosis in injured kidneys. Furthermore, empagliflozin increased renal glycogen synthase kinase 3β (GSK-3β) phosphorylation post I/R. Pharmacological inhibition of GSK-3β activity mimicked the renal protective effects offered by empagliflozin. In summary, these results support a protective role of empagliflozin against renal I/R injury.

Pulmonary ischemia and reperfusion (I/R) injury occurs in many clinical conditions and causes severe damage to the lungs. Diabetes mellitus (DM) predisposes to pulmonary I/R injury. We previously found that remote liver ischemia preconditioning protected lungs against pulmonary I/R injury. The aim of the present study was to investigate whether remote liver ischemic postconditioning (RLIPost) attenuates pulmonary damage induced by I/R injury in non-diabetic or diabetic rats. Male Sprague-Dawley rats were assigned into non-diabetic and diabetic groups. All rats except for the sham were exposed to 45 min of left hilum occlusion followed by 2 h of reperfusion. RLIPost was conducted at the onset of pulmonary reperfusion by four cycles of 5 min of liver ischemia and reperfusion. Lung injury was assessed by the wet/dry weight ratio, pulmonary oxygenation, histopathological changes, apoptosis and the expression of inflammatory cytokines. Reperfusion-associated protein phosphorylation states were determined. RLIPost offered strong pulmonary-protection in both non-diabetic and diabetic rats, as reflected in reduced water content and pulmonary structural damage, recovery of lung function, inhibition of apoptosis and inflammation after ischemia-reperfusion. RLIPost induced the activation of pulmonary STAT-3, a key component in the SAFE pathway, but not activation of the proteins in the RISK pathway, in non-diabetic rats. In contrast, RLIPost-induced pulmonary protection in diabetic lungs was independent of SAFE or RISK pathway activation. These results demonstrate that RLIPost exerts pulmonary protection against I/R-induced lung injury in non-diabetic and diabetic rats. The underlying mechanism for protection may be different in non-diabetic (STAT-3 dependent) versus diabetic (STAT-3 independent) rats.