Anesthetic Induction With Etomidate in Cardiac Surgical Patients: A PRISMA-Compliant Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to systematically review the effects of etomidate (ETM) during anesthetic induction on patients undergoing cardiac surgery. DESIGN: Systematic review and meta-analysis. SETTING: Operating room. PARTICIPANTS: Patients undergoing cardiac surgery. INTERVENTIONS: ETM or control drugs. MEASUREMENTS AND MAIN RESULTS: PubMed, Cochrane Library, OVID, and EMBASE were searched through August 31, 2020. Primary outcomes included hemodynamic profiles and stress responses. Secondary outcomes included morbidity, mortality, and postoperative recovery. For continuous/dichotomous variables, treatment effects were calculated as weighted mean difference (WMD)/odds ratio (OR) and 95% confidence interval (CI). A database search yielded 18 randomized controlled trials including 1,241 patients. The present meta-analysis demonstrated that ETM-anesthetized patients had lower heart rates (WMD, -3.31; 95% CI -5.43 to -1.19; p = 0.002), higher blood pressures (systolic blood pressure: WMD, 12.02; 95% CI 6.24 to 17.80; p < 0.0001; diastolic blood pressure: WMD, 5.23; 95% CI 2.39 to 8.08; p = 0.0003; mean arterial pressure (MAP): WMD, 8.64; 95% CI 5.85 to 11.43; p < 0.00001), less requirement for vasopressor (OR, 0.26; 95% CI 0.15 to 0.44; p < 0.00001), and more nitroglycerin usage (OR, 14.89; 95% CI 4.92 to 45.08; p < 0.00001) during anesthetic induction. Current meta-analysis also demonstrated that single-dose ETM lowered cortisol levels transiently and did not have a significant effect on endogenous norepinephrine and epinephrine levels and was not associated with increased postoperative inotrope and/or vasopressor requirement. Additionally, the meta-analysis suggested that ETM anesthesia was associated with neither increased mortality nor morbidity, except a higher incidence of transient adrenal insufficiency in ETM recipients. CONCLUSION: The present meta-analysis suggested that single-dose ETM during anesthetic induction could be associated with more stable hemodynamics, transient and reversible lower cortisol levels, and a higher adrenal insufficiency incidence, but not worse outcomes in cardiac surgical patients.

Age-associated differences in response to sevoflurane postconditioning in rats.

BACKGROUND: Experimental evidence suggests that anesthetic preconditioning and postconditioning could effectively attenuate myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed at investigating whether there are age-associated differences in response to sevoflurane postconditioning during myocardial I/R injury in young and old rats, and explore the underlying molecular mechanisms. METHODS: Young and old rats were subjected to 30 min myocardial ischemia, followed by 2 h of reperfusion, with or without sevoflurane postconditioning. RESULTS: Both 1 and 2 minimal aveolar concentration (MAC) sevoflurane postconditioning reduced infarct size (IS) (34 ± 3% and 32 ± 2% vs. 58 ± 5%, p < 0.05) and apoptotic index (8 ± 1% and 7 ± 1% vs. 15 ± 2%, p < 0.05) in young rats, compared to young control group. In contrast, they could not reduce IS (45 ± 3% and 43 ± 3% vs. 47 ± 3%, p > 0.05) and apoptotic index (28 ± 3% and 25 ± 2%, vs. 26 ± 2%, p > 0.05) in old rats, compared to old control group. Mechanistically, we found that the phosphorylation of both Akt and ERK1/2 but not STAT3 was substantially enhanced after sevoflurane postconditioning in young rats, compared to young control group, but not in old rats, relative to old control group. CONCLUSION: There are age-related differences after exposure to sevoflurane postconditioning that protects young, but not old rat hearts against I/R injury, which may be at least associated with the inability to activate Akt and ERK1/2.

[Application research of percutaneous patent ductus arteriosus closure by femoral vein approach under echocardiography guidance].

OBJECTIVE: To avoid the injuries of radiation and contrast agent, we assess the efficacy and safety of percutaneous patent ductus arteriosus (PDA) closure by femoral vein approach solely under echocardiography guidance. METHODS: From January 2014 to December 2014, 25 patients in Fuwai hospital with PDA were selected, with mean age (4.5 ± 2.1) years and mean body weight (19 ± 7) kg. The mean diameter of PDA was (5.9 ± 1.2) mm. Patients were all treated by percutaneous PDA closure solely by echocardiography guidance in femoral vein. The effect of the procedure was evaluated by echocardiography. Follow-up was given at one month after procedure. RESULTS: Twenty-three cases were successfully treated with percutaneous PDA closure by femoral vein approach solely under echocardiography guidance, while two patients was closed by femoral artery approach because guide wires could not pass through PDA. The procedural time was (33 ± 5) min. The mean diameter of PDA occluder was (11.4 ± 1.5) mm. Postoperative early trivial residual shunt occurred in three patients. All patients survived with no peripheral vascular injury or complications such as cardiac perforation. Hospitalization time was (3.6 ± 0.8) days. At one month follow-up, no complications such as residual shunt or pericardial effusion were occurred. CONCLUSION: Echocardiography guided percutaneous PDA closure by femoral vein approach is safe and effective, and avoids the use of radiation and contrast agents.

[Safety and efficacy of percutaneous patent ductus arteriosus closure solely under thoracic echocardiography guidance].

OBJECTIVE: To avoid the radiation injuries and use of contrast agent, we assessed the safety and efficacy of percutaneous patent ductus arteriosus closure solely under thoracic echocardiography guidance. METHODS: From June 2013 to June 2014, thirty patients (mean age: (6.3 ± 2.5) years, mean body weight:(22.5 ± 7.3) kg) with pure patent ductus arteriosus were continuously included in this study. The mean diameter of patent ductus arteriosus was (3.8 ± 0.9) mm. Patients were all treated by percutaneous patent ductus arteriosus closure via right femoral artery solely under thoracic echocardiography guidance. The efficacy of the procedure was evaluated by thoracic echocardiography. Follow-up was performed at one month after procedure. RESULTS: All 30 cases were successfully treated with percutaneous patent ductus arteriosus closure solely under thracic echocardiography guidance. The procedural time was (32.8 ± 5.7) minutes. The mean diameter of Amplatzer ADO II was (4.9 ± 1.0) mm. Postoperative trivial residual shunt occurred in six patients immediately after the procedure. All patients survived without peripheral vascular injury or complications such as cardiac perforation. Hospitalization time was (3.4 ± 0.7) days. At one-month follow-up, no complications such as residual shunt or pericardial effusion were observed. CONCLUSION: Echocardiography guided percutaneous patent ductus arteriosus closure by femoral artery approach is safe and effective, and can avoid X-ray and the use of contrast agents.

Delayed remote preconditioning induces cardioprotection: role of heme oxygenase-1.

BACKGROUND: The role of heme oxygenase-1 (HO-1) in the cardioprotection induced by delayed remote ischemic preconditioning (DRIPC) has not been investigated. Therefore, this study was designed to investigate whether HO-1 is involved in DRIPC-mediated cardioprotection in an isolated perfused rat heart model. MATERIALS AND METHODS: Isolated rat hearts were subjected to 30 min ischemia followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size, myocardial troponin levels, and heart function were measured. The protein and messenger RNA levels of HO-1 were determined. RESULTS: DRIPC facilitated postischemic cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group (10.22 ± 2.57%) than the D1RIPC group (22.34 ± 4.02%, P < 0.001) or the D2RIPC group (14.60 ± 3.13%, P = 0.034). These effects in the D1RIPC group could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor). DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein expression (D1RIPC, 0.11 ± 0.03; versus 0.15 ± 0.06 in the D2RIPC group, P = 0.06; versus 0.20 ± 0.04 in the D3RIPC group, P = 0.04) and messenger RNA levels of HO-1 expression. CONCLUSIONS: Our findings suggest that HO-1 is involved in the cardioprotection induced by DRIPC, and that increase in the number of preconditioning stimuli may enhance cardioprotective effects accompanied with increased HO-1 level.

Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats.

AIM: Sevoflurane postconditioning (SpostC) has been shown to protect the heart from ischemia-reperfusion (I/R) injury. In this study, we examined whether SpostC affected autophagic flux in myocardial tissues that contributed to its cardioprotective effects in rats following acute I/R injury. METHODS: SD rats underwent 30 min of left anterior descending coronary artery ligation followed by 120 min of reperfusion. The rats were subjected to inhalation of 2.4% (v/v) sevoflurane during the first 5 min of reperfusion, and chloroquine (10 mg/kg, ip) was injected 1 h before I/R. Myocardial infarct size was estimated using TTC staining. Autophagosomes in myocardial tissues were detected under TEM. Expression of LC3B-II, beclin-1, p62/SQSTM1, cathepsin B, caspase-3 and cleaved PARP was assessed using Western blot analysis. Plasma cardiac troponin I was measured using ELISA. Cardiomyocyte apoptosis was evaluated with TUNEL staining. RESULTS: I/R procedure produced severe myocardium infarct and apoptosis accompanied by markedly increased number of autophagosomes, as well as increased levels of LC3B-II, beclin-1 and p62 in myocardial tissues. SpostC significantly reduced infarct size, attenuated myocardial apoptosis, restored intact autophagic flux and improved the lysosomal function in myocardial tissues. Administration of chloroquine that blocked autophagic flux abrogated the cardioprotective effects of SpostC. CONCLUSION: SpostC exerts its cardioprotective effects in rats following I/R injury via restoring autophagic flux in myocardial tissues.

ß-blockers and volatile anesthetics may attenuate cardioprotection by remote preconditioning in adult cardiac surgery: a meta-analysis of 15 randomized trials.

OBJECTIVE: Clinical trials on cardioprotection by remote ischemic preconditioning (RIPC) for adult patients undergoing cardiac surgery revealed mixed results. Previous meta-analyses have been conducted and found marked heterogeneity among studies. The aim of this meta-analysis was to evaluate the factors affecting cardioprotection by remote preconditioning in adult cardiac surgery. DESIGN: A meta-analysis of randomized controlled trials. SETTING: University hospitals. PARTICIPANTS: Adult subjects undergoing cardiac surgery. INTERVENTIONS: RIPC. MEASUREMENTS AND MAIN RESULTS: Fifteen trials with a total of 1,155 study patients reporting postoperative myocardial biomarker (CK-MB or troponin) levels were identified from PubMed, Embase, and the Cochrane Library (up to July 2012). Compared with controls, RIPC significantly reduced postoperative biomarkers of myocardial injury (standardized mean difference = -0.31, p = 0.041; heterogeneity test: I(2) = 83.5%). This effect seemed more significant in valve surgery (standardized mean difference = -0.74, p = 0.002) than in coronary artery surgery (standardized mean difference = -0.23; p = 0.17). Univariate meta-regression analyses suggested that the major sources of significant heterogeneity were ß-blockers (%) (coefficient = 0.0161, p = 0.022, adjusted R(2) = 0.37) and volatile anesthetics (coefficient = 0.6617, p = 0.065, adjusted R(2) = 0.22). These results were further confirmed in multivariate regression and subgroup analyses. CONCLUSIONS: Available data from this meta-analysis further confirmed the cardioprotection conferred by RIPC in adult cardiac surgery. Moreover, the cardioprotective effect may be attenuated when combined with ß-blockers or volatile anesthetics.

Sevoflurane postconditioning attenuates reperfusion-induced ventricular arrhythmias in isolated rat hearts exposed to ischemia/reperfusion injury.

Sevoflurane postconditioning has been proven to protect the hearts against ischemia/reperfusion injury, manifested mainly by improved cardiac function, reduced myocardial specific biomarker release, and decreased infarct size. This study is to observe the effects of sevoflurane postconditioning on reperfusion-induced ventricular arrhythmias and reactive oxygen species generation in Langendorff perfused rat hearts. Compared with the unprotected hearts subjected to 25 min of global ischemia followed by 30 min of reperfusion, exposure of 3% sevoflurane during the first 15 min of reperfusion significantly improved cardiac function, reduced cardiac troponin I release, decreased infarct size and attenuated reperfusion-induced ventricular arrhythmia. Further analysis on arrhythmia during the 30 min of reperfusion showed that, sevoflurane postconditioning decreased both the duration and incidence of ventricular tachycardia and ventricular fibrillation. In the meantime, intracellular malondialdehyde and reactive oxygen species levels were also reduced. These above results demonstrate that sevoflurane postconditioning protects the hearts against ischemia/reperfusion injury and attenuates reperfusion-induced arrhythmia, which may be associated with the regulation of lipid peroxidation and reactive oxygen species generation.

Attenuation of ischemia-reperfusion injury by sevoflurane postconditioning involves protein kinase B and glycogen synthase kinase 3 beta activation in isolated rat hearts.

Volatile anesthetic ischemic postconditioning reduces infarct size following ischemia/reperfusion. Whether phosphorylation of protein kinase B (PKB/Akt) and glycogen synthase kinase 3 beta (GSK3ß) is causal for cardioprotection by postconditioning is controversial. We therefore investigated the impact of PKB/Akt and GSK3ß in isolated perfused rat hearts subjected to 40 min of ischemia followed by 1 h of reperfusion. 2.0% sevoflurane (1.0 minimum alveolar concentration) was administered at the onset of reperfusion in 15 min as postconditioning. Western blot analysis was used to determine phosphorylation of PKB/Akt and its downstream target GSK3ß after 1 h of reperfusion. Mitochondrial and cytosolic content of cytochrome C checked by western blot served as a marker for mitochondrial permeability transition pore opening. Sevoflurane postconditioning significantly improved functional cardiac recovery and decreased infarct size in isolated rat hearts. Compared with unprotected hearts, sevoflurane postconditioning-induced phosphorylation of PKB/Akt and GSK3ß were significantly increased. Increase of cytochrome C in mitochondria and decrease of it in cytosol is significant when compared with unprotected ones which have reversal effects on cytochrome C. The current study presents evidence that sevoflurane-induced cardioprotection at the onset of reperfusion are partly through activation of PKB/Akt and GSK3ß.

Ulinastatin reduces postoperative bleeding and red blood cell transfusion in patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Ulinastatin is a type of glycoprotein and a nonspecific wide-spectrum protease inhibitor like antifibrinolytic agent aprotinin. Whether Ulinastatin has similar beneficial effects on blood conservation in cardiac surgical patients as aprotinin remains undetermined. Therefore, a systematic review and meta-analysis were performed to evaluate the effects of Ulinastatin on perioperative bleeding and transfusion in patients who underwent cardiac surgery. METHODS: Electronic databases were searched to identify all clinical trials comparing Ulinastatin with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Primary outcomes included perioperative blood loss, blood transfusion, postoperative re-exploration for bleeding. Secondary outcomes include perioperative hemoglobin level, platelet counts and functions, coagulation tests, inflammatory cytokines level, and so on. For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Statistical significance was defined as P < .05. RESULTS: Our search yielded 21 studies including 1310 patients, and 617 patients were allocated into Ulinastatin group and 693 into Control (placebo/blank) group. There was no significant difference in intraoperative bleeding volume, postoperative re-exploration for bleeding incidence, intraoperative red blood cell transfusion units, postoperative fresh frozen plasma transfusion volumes and platelet concentrates transfusion units between the 2 groups (all P > .05). Ulinastatin reduces postoperative bleeding (WMD = -0.73, 95% CI: -1.17 to -0.28, P = .001) and red blood cell (RBC) transfusion (WMD = -0.70, 95% CI: -1.26 to -0.14, P = .01), inhibits hyperfibrinolysis as manifested by lower level of postoperative D-dimer (WMD = -0.87, 95% CI: -1.34 to -0.39, P = .0003). CONCLUSION: This meta-analysis has found some evidence showing that Ulinastatin reduces postoperative bleeding and RBC transfusion in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Ulinastatin.

Predictors of prolonged mechanical ventilation after aortic arch surgery with deep hypothermic circulatory arrest plus antegrade selective cerebral perfusion.

OBJECTIVE: The predictors of prolonged mechanical ventilation after aortic arch surgery with deep hypothermic circulatory arrest have not been comprehensively evaluated. The present study was designed to identify variables associated with prolonged ventilation in a group of aortic arch surgery patients from a single center. DESIGN: A retrospective study. Prolonged mechanical ventilation was defined as >72 hours. SETTING: Cardiovascular operating rooms and the intensive care unit. PARTICIPANTS: Adults requiring aortic arch surgery with deep hypothermic circulatory arrest plus antegrade selective cerebral perfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 7 patients who underwent 1-stage total or subtotal aortic replacement were excluded, 255 patients were enrolled in the study. The average age of the patients was 44.7 +/- 10.8 years with male predominance (74.1%). Two hundred twenty-nine patients were extubated within 72 hours postoperatively, and 26 patients needed prolonged mechanical ventilation. Patients with prolonged mechanical ventilation had higher incidences of in-hospital mortality, stroke, and renal failure requiring dialysis and reintubation and stayed longer in the intensive care unit and hospital than those without prolonged ventilation (p < 0.05). In multivariate analysis, predictors of prolonged ventilation were found to be prolonged cardiopulmonary bypass time, advanced age, emergency, and preoperative serum creatinine level (p < 0.05). CONCLUSION: The authors identified 4 preoperative and intraoperative predictors associated with increased risk of prolonged mechanical ventilation. This is helpful to identify patients with increased risk for prolonged ventilation, develop preemptive strategies, and allocate medical resources.

[Predictors of prolonged intensive care unit stay in patients undergoing aortic arch replacement].

OBJECTIVE: To identify the predictors of prolonged intensive care unit (ICU) stay in patients undergoing aortic arch replacement. METHODS: The clinical data of 173 consecutive patients undergoing aortic arch replacement requiring deep hypothermic circulatory arrest plus antegrade selective cerebral perfusion were reviewed retrospectively. Patients who had undergone one-stage total or subtotal aortic replacement were excluded. Data collected from records were used to identify univariate and multivariate predictors for prolonged ICU stay, which was defined as longer than 5 days in ICU postoperatively. RESULTS: Patients aged (45.4 +/- 10. 6) years and male accounted for 76.3%. The incidence of prolonged ICU stay was 22.0%. The incidences of postoperative stroke and acute renal failure were 6.4% and 4.6%, respectively. The in-hospital mortality rate was 2.9%. Univariate predictors for prolonged ICU stay included body mass index, preoperative serum creatinine level, emergent surgery, coronary artery bypass grafting at the same time, cardiopulmonary bypass time, myocardial ischemic time, and occurrence of postoperative stroke and/or acute renal failure. Multivariable modeling identified that emergent surgery (odds ratio [95% confidence interval] -3.1 [1.3, 7.6]), cardiopulmonary bypass time longer than 180 min (3.3 [1.4, 8.1]), postoperative stroke (6.9 [1.1, 43.1]) and acute renal failure (14.5 [1.3, 161.6]) were the independent predictors for prolonged ICU stay. CONCLUSIONS: The incidence of prolonged ICU stay is high after aortic arch replacement. Patients with identified multivariate predictors carry a higher risk of prolonged ICU stay and may benefit from enhanced perioperative protection of brain and kidney.

Hemocoagulase reduces postoperative bleeding and blood transfusion in cardiac surgical patients: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Hemocoagulase is isolated and purified from snake venoms. Hemocoagulase agents have been widely used in the prevention and treatment of surgical bleeding. A systematic review was performed to evaluate the effects of hemocoagulase on postoperative bleeding and transfusion in patients who underwent cardiac surgery. METHODS: Electronic databases were searched to identify all clinical trials comparing hemocoagulase with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Two authors independently extracted perioperative data and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. Sensitivity analyses were done by examining the influence of statistical model and individual trial on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P < .05. RESULTS: Our search yielded 12 studies including 900 patients, and 510 patients were allocated into hemocoagulase group and 390 into control group. Meta-analysis suggested that, hemocoagulase-treated patients had less bleeding volume, reduced red blood cells and fresh frozen plasma transfusion, and higher hemoglobin level than those of controlled patients postoperatively. Meta-analysis also showed that, hemocoagulase did not influence intraoperative heparin or protamine dosages and postoperative platelet counts. Meta-analysis demonstrated that, hemocoagulase-treated patients had significantly shorter postoperative prothrombin time, activated partial thromboplastin time, and thrombin time, higher fibrinogen level and similar D-dimer level when compared to control patients. CONCLUSION: This meta-analysis has found some evidence showing that hemocoagulase reduces postoperative bleeding, and blood transfusion requirement in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Hemocoagulase.

Outcomes of different rehabilitative procedures in patients with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries.

OBJECTIVES: The objective of this study was to compare our clinical outcomes of the central shunt and the right ventricle-pulmonary artery (RV-PA) connection in patients with pulmonary atresia, ventricular septal defect and the major aortopulmonary collateral arteries. METHODS: From November 2009 to October 2017, a total of 157 consecutive patients with pulmonary atresia, ventricular septal defect, the major aortopulmonary collateral arteries and the hypoplastic PAs who underwent palliative surgery were included. Seventy patients underwent the central shunt (the central shunt group) and 87 patients underwent the RV-PA connection (the RV-PA group). Propensity score matching was used to create 2 cohorts with similar baseline characteristics: 56 central shunt patients were one-to-one-matched with 56 RV-PA connection patients. The early and late outcomes were compared. RESULTS: The median duration of follow-up was 18 months in the central shunt group and 22 months in the RV-PA group (P = 0.10). The probability of complete repair was significantly lower in the central shunt group as compared with the RV-PA group (P = 0.048). The Kaplan-Meier estimates of complete repair rates were 47.2 ± 10.0% after 3 years and 56.0 ± 11.6% after 5 years in the central shunt group, which were lower as compared with 62.3 ± 7.6% after 3 years and 74.5 ± 7.2% after 5 years in the RV-PA group. The increase in the mean McGoon ratio and the mean Nakata index were significantly lower in the central shunt group than those in the RV-PA group (0.57 ± 0.52 vs 1.02 ± 0.44, P = 0.036; 98.2 ± 35.1 mm2/m2 vs 176.9 ± 85.4 mm2/m2, P = 0.025, respectively). The in-hospital morbidity and mortality after complete repair were similar between 2 groups. CONCLUSIONS: Compared with the central shunt, the RV-PA connection appears to be a more effective palliative procedure to improve the probability of complete repair and PA growth in patients with pulmonary atresia, ventricular septal defect and the major aortopulmonary collateral arteries, in whom primary repair is not feasible.

Age and Surgical Complexity impact on Renoprotection by Remote Ischemic Preconditioning during Adult Cardiac Surgery: A Meta analysis.

We aimed to conduct an up-to-date meta-analysis to comprehensively assess the renoprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing adult cardiac surgery. 21 randomized controlled trials (RCTs) with a total of 6302 patients were selected and identified. Compared with controls, RIPC significantly reduced the incidence of acute kidney injury (AKI) [odds ratio (OR) = 0.79; P = 0.02; I2 = 38%], and in particular, AKI stage I (OR = 0.65; P = 0.01; I2 = 55%). RIPC significantly shortened mechanical ventilation (MV) duration [weighted mean difference (WMD) = -0.79 hours; P = 0.002; I2 = 53%), and reduced intensive care unit (ICU) stay (WMD = -0.23 days; P = 0.07; I2 = 96%). Univariate meta-regression analyses showed that the major sources of heterogeneity for AKI stage I were age (coefficient = 0.06; P = 0.01; adjusted R2 = 0.86) and proportion of complex surgery (coefficient = 0.02; P = 0.03; adjusted R2 = 0.81). Subsequent multivariate regression and subgroup analyses also confirmed these results. The present meta-analysis suggests that RIPC reduces the incidence of AKI in adults undergoing cardiac surgery and this benefit was more pronounced in younger patients undergoing non-complex cardiac surgery. RIPC may also shorten MV duration and ICU stay. Future RCTs tailored for those most likely to benefit from RIPC warrants further investigation.

Sevoflurane postconditioning alleviates action potential duration shortening and L-type calcium current suppression induced by ischemia/reperfusion injury in rat epicardial myocytes.

BACKGROUND: It has been proved that sevoflurane postconditioning (SpostC) could protect the heart against myocardial ischemia/reperfusion injury, however, there has been few research focused on the electrophysiological effects of SpostC. The objective of the study was to investigate the effects of SpostC on action potential duration (APD) and L-type calcium current (I(Ca, L)) in isolated cardiomyocytes. METHODS: Langendorff perfused SD rat hearts were randomly assigned to one of the time control (TC), ischemia/reperfusion (I/R, 25 minutes of ischemia followed by 30 minutes of reperfusion), and SpostC (postconditioned with 3% sevoflurane) groups. At the end of reperfusion, epicardial myocytes were dissociated enzymatically for patch clamp studies. RESULTS: Sevoflurane directly prolonged APD and decreased peak I(Ca, L) densities in epicardial myocytes of the TC group (P < 0.05). I/R injury shortened APD and decreased peak I(Ca, L) densities in epicardial myocytes of the I/R group (P < 0.05). SpostC prolonged APD and increased peak I(Ca, L) densities in epicardial myocytes exposed to I/R injury (P < 0.05). SpostC decreased intracellular reactive oxygen species (ROS) levels, reduced the incidence of ventricular tachycardia and ventricular fibrillation, and decreased reperfusion arrhythmia scores compared with the I/R group (all P < 0.05). CONCLUSIONS: SpostC attenuates APD shortening and I(Ca, L) suppression induced by I/R injury. The regulation of APD and I(Ca, L) by SpostC might be related with intracellular ROS modulation, which contributes to the alleviation of reperfusion ventricular arrhythmia.

Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury.

BACKGROUND: Studies suggested that anesthetics administered upon the early reperfusion or "anesthetic postconditioning" could protect post-ischemic hearts against myocardial ischemia reperfusion injury (MIRI). However, the mechanism responsible for such protection was not well-elucidated. We investigated the cardioprotection induced by sevoflurane postconditioning (SpostC) in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase 1 and 2 (ERK 1/2), mitochondrial K(ATP) channels (mitoK(ATP)) and mitochondrial permeability transition pore (mPTP), by selectively inhibiting PI3K, ERK 1/2, mitoK(ATP), with LY294002 (LY), PD98059 (PD), 5-hydroxydecanoate (5-HD) and by directly opening of mPTP with atractyloside (ATR), respectively. METHODS: Isolated rat hearts were randomly assigned to one of the 12 groups (n = 15): Time control (continuous perfusion), ISCH (30 minutes of ischemia followed by 60 minutes of reperfusion alone), SpostC (3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia), ISCH + LY, ISCH + PD, ISCH + ATR, ISCH + 5-HD and ISCH + dimethyl sulfoxide (DMSO) groups (LY, PD, ATR, 5-HD and DMSO (the vehicle) was administered respectively during the first 15 minutes of reperfusion following test ischemia), SpostC + LY, SpostC + PD, SpostC + ATR and SpostC + 5-HD groups (LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively). Hemodynamics was compared within and between groups. Infarction size was determined at the end of experiments using triphenyltetrazolium chloride (TTC) staining. Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) released from necrotic myocardium, were compared among TC, ISCH and SpostC groups. To investigate the relationships between RISK and mPTP implicated in SpostC, NAD(+) content in myocardium, a marker of mPTP opening, was compared among some experimental groups (TC, ISCH, ISCH + LY, ISCH + PD, ISCH + DMSO, SpostC, SpostC + LY, SpostC + PD). To further investigate whether the anti-apoptotic mechanism is implicated in SpostC-induced cardioprotection and its association with mitochondria, TUNEL staining was performed in some experimental groups (TC, ISCH, ISCH + 5-HD, ISCH + ATR, ISCH + DMSO, SpostC, SpostC + 5-HD, SpostC + ATR). RESULTS: When compared with unprotected hearts subjected to 30 minutes of ischemia, exposure to 3% sevoflurane for 15 minutes during early reperfusion significantly improved functional recovery, decreased myocardial infarct size, decreased LDH, CK-MB and cTnI release, and decreased cardiomyocyte apoptosis (P < 0.05). However, such cardioprotective effects of hemodynamic recovery and infarct size reduction by sevoflurane was completely abolished by any one of LY294002, PD98059, atractyloside and 5-hydroxydecanoate (P < 0.05). Additionally, either LY294002 or PD98059 could reverse the inhibitory effect of SpostC over mPTP opening upon reperfusion (P < 0.05). Both atractyloside and 5-hydroxydecanoate could abrogate the anti-apoptotic effects of SpostC (P < 0.05). CONCLUSION: These findings demonstrate that PI3K, ERK 1/2, mitoK(ATP) and mPTP are key players in sevoflurane postconditioning induced cardioprotective mechanisms in isolated rat hearts subjected to MIRI.