ABSTRACT
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 Pâ<â.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 Pâ>â.05). Ulinastatin reduces postoperative bleeding (WMD = -0.73, 95% CI: -1.17 to -0.28, Pâ=â.001) and red blood cell (RBC) transfusion (WMDâ=â-0.70, 95% CI: -1.26 to -0.14, Pâ=â.01), inhibits hyperfibrinolysis as manifested by lower level of postoperative D-dimer (WMDâ=â-0.87, 95% CI: -1.34 to -0.39, Pâ=â.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.
Subject(s)
Blood Transfusion/statistics & numerical data , Cardiac Surgical Procedures , Glycoproteins/therapeutic use , Postoperative Hemorrhage/prevention & control , Trypsin Inhibitors/therapeutic use , Blood Coagulation/drug effects , Blood Platelets/drug effects , Glycoproteins/pharmacology , Humans , Trypsin Inhibitors/pharmacologyABSTRACT
BACKGROUND:: Calcium regulatory proteins-L-type Ca2+ channels (LTCCs), ryanodine receptor 2 (RyR2), and Na+/Ca2+ exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model. METHODS:: After 30-min balanced perfusion, isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion. Totally 40 isolated hearts were randomly assigned to four groups (n = 10/group): time control group, I/RI group, SevoPoC group, and DRIPC group. The effect of SevoPoC (3% v/v) and DRIPC were observed. Myocardial infarct size (IS), cardiac troponin I level, and heart function were measured. The protein and messenger RNA levels of LTCCs, RyR2, and NCX1 were determined. RESULTS:: Both SevoPoC and DRIPC improved the recovery of myocardial function, and reduced cardiac troponin I release after I/RI. The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group (16.50% ± 4.54% in the SevoPoC group [P = 0.0006], and 22.34% ± 4.02% in the DRIPC group [P = 0.0007] vs. 35.00% ± 5.24% in the I/RI group, respectively). SevoPoC, but not DRIPC significantly inhibited the activity of NCX1 (0.59 ± 0.09 in the I/RI group vs. 0.32 ± 0.16 in the SevoPoC group, P = 0.006; vs. 0.57 ± 0.14 in the DRIPC group, P = 0.072). No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC. In addition, subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin I level and the protein expression of NCX1 (r = 0.505, P = 0.023). CONCLUSION:: SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.
Subject(s)
Methyl Ethers/therapeutic use , Sodium-Calcium Exchanger/metabolism , Animals , Heart/drug effects , Hemodynamics , Ischemic Preconditioning/methods , Ischemic Preconditioning, Myocardial/methods , Male , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Protein Isoforms/metabolism , Rats , Rats, Sprague-Dawley , Sevoflurane , Sodium-Calcium Exchanger/geneticsABSTRACT
BACKGROUND: The study aimed to investigate the influence of in vitro storage on erythrocyte complement receptor one (E-CR1), cell shrinkage and eryptosis of human red blood cells (RBCs), and to assess the possible effects of ulinastatin (UTI) on them. METHODS: After collection, RBCs were treated with saline (control group) and different concentrations of UTI (5,000 U/mL, 10,000 U/mL, and 50,000 U/mL in Group C1, Group C2, and Group C3, respectively). E-CR1, cell size, and phosphatidylserine (PS) exposure and intracellular Ca2+ concentration were analyzed by flow cytometer every 7 days up to Day 35. RESULTS: E-CR1 level and cell size of all groups decreased during storage. In the control group, E-CR1 began to decrease on Day 28 and cells shrank on Day 21. The E-CR1 level of Group C2 was significantly higher than that of the control group beginning on Day 21. The cells of Group C1 and Group C2 began to shrink remarkably on Day 21, and those of Group C3 on Day 35. PS-exposure levels of 4 groups started to increase on Day 7 (p < 0.05), while from Day 14 to 35 those of Group C3 were significantly lower than the control group (p < 0.05). The intracellular Ca2+ levels of the control group started to increase significantly on Day 7, one week earlier than the experimental groups. From Day 21 to 35, the intracellular Ca2+ levels of Group C2 and C3 were significantly lower than those of the control group (p < 0.05). CONCLUSIONS: RBCs underwent E-CR1 loss, cell shrinkage, and eryptosis during in vitro storage, which could be attenuated by UTI.
Subject(s)
Erythrocytes , Cell Size , Erythrocyte Count , Flow Cytometry , Humans , PhosphatidylserinesABSTRACT
BACKGROUND: Delirium is a frequent complication after cardiac surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the impact of perioperative dexmedetomidine administration on the incidence of delirium in elderly patients after cardiac surgery. METHODS: This randomized, double-blinded, and placebo-controlled trial was conducted in two tertiary hospitals in Beijing between December 1, 2014 and July 19, 2015. Eligible patients were randomized into two groups. Dexmedetomidine (DEX) was administered during anesthesia and early postoperative period for patients in the DEX group, whereas normal saline was administered in the same rate for the same duration for patients in the control (CTRL) group. The primary endpoint was the incidence of delirium during the first five days after surgery. Secondary endpoints included the cognitive function assessed on postoperative days 6 and 30, the overall incidence of non-delirium complications within 30 days after surgery, and the all-cause 30-day mortality. RESULTS: Two hundred eighty-five patients were enrolled and randomized. Dexmedetomidine did not decrease the incidence of delirium (4.9% [7/142] in the DEX group vs 7.7% [11/143] in the CTRL group; OR 0.62, 95% CI 0.23 to 1.65, p = 0.341). Secondary endpoints were similar between the two groups; however, the incidence of pulmonary complications was slightly decreased (OR 0.51, 95% CI 0.26 to 1.00, p = 0.050) and the percentage of early extubation was significantly increased (OR 3.32, 95% CI 1.36 to 8.08, p = 0.008) in the DEX group. Dexmedetomidine decreased the required treatment for intraoperative tachycardia (21.1% [30/142] in the DEX group vs 33.6% [48/143] in the CTRL group, p = 0.019), but increased the required treatment for postoperative hypotension (84.5% [120/142] in the DEX group vs 69.9% [100/143] in the CTRL group, p = 0.003). CONCLUSIONS: Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of postoperative delirium in elderly patients undergoing elective cardiac surgery. However, considering the low delirium incidence, the trial might have been underpowered. TRIAL REGISTRATION: ClinicalTrials.gov NCT02267538.
Subject(s)
Cardiac Surgical Procedures , Dexmedetomidine/administration & dosage , Dexmedetomidine/adverse effects , Emergence Delirium , Age Factors , Aged , Aged, 80 and over , Double-Blind Method , Emergence Delirium/chemically induced , Emergence Delirium/mortality , Female , Humans , Incidence , Male , Postoperative Period , Time FactorsABSTRACT
OBJECTIVE: To examine whether the combination of anesthetic preconditioning and anesthetic postconditioning could elicit additional cardio-protection as compared to either anesthetic preconditioning or anesthetic postconditioning alone and its underlying mechanism. METHODS: Isolated rat hearts were randomized into one of four groups: CTRL group (30 min of ischemia followed by 120 min of reperfusion alone); SpreC group (3% sevoflurane preconditioning was administered for 15 min followed by 10 min of washout before ischemia); SpostC group (3% sevoflurane postconditioning was administered during the first 15 min of reperfusion after ischemia); SpreC+SpostC group (the protocols of SpreC and SpostC were combined). Hemodynamics, myocardial infarct size, lactate dehydrogenase and creatine kinase-MB in collected effluent, phosphorylation of PKB/Akt and ERK 1/2 and content of nicotinamide adenine dinucleotide in the left ventricular tissue were compared among the four groups. RESULTS: When compared with unprotected Control hearts, those in the sevoflurane-treated groups (SpreC, SpostC and SpreC+SpostC) showed significantly better functional recovery, reduced myocardial infarct size and decreased lactate dehydrogenase and creatine kinase-MB release. Comparison of the above-mentioned variables among the three sevoflurane-treated groups showed that maximal cardio-protection was obtained in the SpreC+SpostC group. Both SpreC and SpreC+SpostC induced a biphasic response in protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK 1/2) phosphorylation, while SpostC induced only one phase. The effects on phosphorylation of both PKB/Akt and ERK 1/2 induced by SpreC and SpostC were found to be additive during reperfusion. The combination of SpreC and SpostC also had additive effects on inhibiting mitochondrial permeability transition pore (mPTP) opening induced by ischemia-reperfusion. CONCLUSION: These findings suggested that the cardio-protection induced by SpreC and SpostC could be additive via the involvement of PKB/Akt, ERK 1/2 and mPTP.
Subject(s)
Methyl Ethers/pharmacology , Myocardial Reperfusion Injury/prevention & control , Myocardium/metabolism , Animals , Cardiotonic Agents , Hemodynamics , Male , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Permeability Transition Pore , Mitogen-Activated Protein Kinase 3/metabolism , Muscle Proteins/metabolism , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardium/pathology , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , SevofluraneABSTRACT
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.
Subject(s)
Anesthetics, Inhalation/therapeutic use , Autophagy/drug effects , Cardiotonic Agents/therapeutic use , Methyl Ethers/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Myocardium/pathology , Animals , Heart/drug effects , Male , Myocardial Infarction/etiology , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/complications , Myocardial Reperfusion Injury/pathology , Rats, Sprague-Dawley , SevofluraneABSTRACT
CONTEXT: Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction. OBJECTIVE: To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery. DESIGN: Prospective cohort study. SETTING: Two teaching hospitals. PATIENTS: One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009. INTERVENTION: None. MAIN OUTCOME MEASURES: Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction. RESULTS: Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016). CONCLUSIONS: High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery.
Subject(s)
Cognition Disorders/blood , Cognition Disorders/physiopathology , Coronary Artery Bypass/adverse effects , Hydrocortisone/blood , Postoperative Complications/blood , Postoperative Complications/physiopathology , Adult , Cognition Disorders/etiology , Cohort Studies , Female , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Period , Prospective Studies , RiskABSTRACT
OBJECTIVE: To evaluate the effectiveness and safty of tranexamic acid in patients receiving on-pump coronary artery bypass grafting (CABG) without clopidogrel and aspirin cessation. METHODS: The current study is a prospective, randomized and placebo-control trial. A total of 116 patients receiving selective on-pump CABG with their last ingestion of clopidogrle and aspirin within 7 days preoperatively were recruited. Despite 6 patients withdrawal their consent, the rest 110 were randomized to receive tranexamic acid or placebo. The tranexamic acid regimen was a bolus of 10 mg/kg followed by a maintenance of 10 mg·kg(-1)·h(-1) throughout the surgery. The primary outcome was the volume of allogeneic erythrocyte transfused perioperatively. RESULTS: Baseline characteristics were comparable between the groups. In patients receiving tranexamic acid and placebo respectively, the volume of allogeneic erythrocyte transfused was 4.0 (7.5) units and 6.0(6.0) units (W = 1021, P < 0.01). In these 2 groups respectively, blood loss was 930 (750) ml and 1210 (910) ml (W = 1042, P < 0.01), the incidence of major bleeding was 50.9% and 76.4% (χ(2) = 7.70, P < 0.01), the incidence of reoperation was 0 and 9.1% (χ(2) = 5.24, P = 0.02); the volume of plasma transfused was 400 (600) ml and 600 (650) ml (W = 1072, P = 0.01), the exposure of plasma was 60.0% and 85.5% (χ(2) = 8.98, P < 0.01) and the exposure to any allogeneic blood products was 85.5% and 98.2% (χ(2) = 5.93, P = 0.01). Perioperative mortality, morbidity and the incidence of adverse events were balanced between the groups without statistical significance. CONCLUSION: Tranexamic acid reduced significantly postoperative bleeding and transfusion in patients receiving on-pump CABG without clopidogrel and aspirin cessation.
Subject(s)
Coronary Artery Bypass , Postoperative Hemorrhage/prevention & control , Tranexamic Acid/therapeutic use , Aged , Aged, 80 and over , Aspirin/therapeutic use , Blood Transfusion , Clopidogrel , Female , Humans , Male , Middle Aged , Prospective Studies , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Tranexamic Acid/adverse effectsABSTRACT
OBJECTIVE: To summarize the experience in anesthetic management for total thoracoabdominal aorta replacement without cardiopulmonary bypass. METHODS: From October 2009 to September 2010, 10 patients of Fuwai Hospital received off-pump total thoracoabdominal aorta replacement. Of these patients, 5 were subjected to Standford B aortic dissection, 2 were Standford A aortic dissection received total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta.1 were Marfan's syndrome, and 2 were thoracoabdominal aorta. All operations used the technique which preserved blood was transfused back by pump via the femoral artery. RESULTS: The average surgery time was (7.4 ± 1.2) h and extubation time was (14.1 ± 2.5) h, the descending thoracic aorta cross clamp time was (11.5 ± 3.6) min, the intercostal artery reconstruction time was (16.4 ± 5.5) min, the required amount of blood products was fresh frozen plasma (600.5 ± 542.8) ml, platelet(1.7 ± 0.8) U, red blood cell (4.3 ± 2.4) U, auto blood salvage (465.7 ± 242.3) ml. Three patients occurred atelectasis and one patient occurred sero peritoneum postoperation. All of the 10 patients were discharged from hospital without any neurologic complications. CONCLUSION: The anesthetic management for total thoracoabdominal aorta replacement without cardiopulmonary bypass is feasible. It can reduce the side effects of deep hypothermia circulatory arrest and had a good effect.
Subject(s)
Anesthesia/methods , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Thoracic/surgery , Female , Humans , Male , Vascular Surgical Procedures/methodsABSTRACT
BACKGROUND: The association between fish consumption and heart failure (HF) incidence is inconsistent. METHODS: We performed a systematic search of Pubmed and Embase (from 1953 to June 2012) using key words related to fish and HF. Studies with at least three categories of fish consumption reporting both relative risk (RR) and corresponding 95% confidence interval (CI) for HF incidence were included. The pooled RR and 95%CI were calculated using a fixed or random-effects model. The generalized least squares regression model was used to quantify the dose-response relationship between fish consumption and HF incidence. RESULTS: Five prospective cohort studies including 4750 HF events of 170 231 participants with an average of 9.7-year follow-up were selected and identified. Compared with those who never ate fish, individuals with higher fish consumption had a lower HF incidence. The pooled RRs for HF incidence was 0.99 (95%CI, 0.91 to 1.08) for fish consumption 1 to 3 times per month, 0.91 (95%CI, 0.84 to 0.99) for once a week, 0.87 (95%CI, 0.81 to 0.95) for 2 to 4 times per week, and 0.86 (95%CI, 0.84 to 0.99) for 5 or more times per week. An increment of 20 g of daily fish intake was related to a 6% lower risk of HF (RR: 0.94, 95%CI, 0.90 to 0.97; P for trend = 0.001). CONCLUSIONS: This meta-analysis suggests that there is a dose-dependent inverse relationship between fish consumption and HF incidence. Fish intake once or more times a week could reduce HF incidence.
Subject(s)
Fishes , Heart Failure/epidemiology , Animals , Female , Humans , Incidence , Male , Prospective Studies , SeafoodABSTRACT
BACKGROUND: The hybrid procedure for coronary heart disease combines minimally invasive coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) and is an alternative to revascularization treatment. We sought to assess the predictive value of four risk-stratification models for risk assessment of major adverse cardiac and cerebrovascular events (MACCE) in patients with multivessel disease undergoing hybrid coronary revascularization. METHODS: The data of 120 patients were retrospectively collected and the SYNTAX score, EuroSCORE, SinoSCORE and the Global Risk Classification (GRC) calculated for each patient. The outcomes of interest were 2.7-year incidences of MACCE, including death, myocardial infarction, stroke, and any-vessel revascularization. RESULTS: During a mean of 2.7-year follow-up, actuarial survival was 99.17%, and no myocardial infarctions occurred. The discriminatory power (area under curve (AUC)) of the SYNTAX score, EuroSCORE, SinoSCORE and GRC for 2.7-year MACCE was 0.60 (95% confidence interval 0.42 - 0.77), 0.65 (0.47 - 0.82), 0.57 (0.39 - 0.75) and 0.65 (0.46 - 0.83), respectively. The calibration characteristics of the SYNTAX score, EuroSCORE, SinoSCORE and GRC were 3.92 (P = 0.86), 5.39 (P = 0.37), 13.81 (P = 0.32) and 0.02 (P = 0.89), respectively. CONCLUSIONS: In patients with multivessel disease undergoing a hybrid procedure, the SYNTAX score, EuroSCORE, SinoSCORE and GRC were inaccurate in predicting MACCE. Modifying risk-stratification models to improve the predictive value for a hybrid procedure is needed.
Subject(s)
Angioplasty, Balloon, Coronary/methods , Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Coronary Artery Disease/therapy , Aged , Angioplasty, Balloon, Coronary/adverse effects , Coronary Artery Bypass/adverse effects , Coronary Artery Disease/mortality , Female , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Action Potentials/drug effects , Calcium/metabolism , Methyl Ethers/therapeutic use , Pericardium/drug effects , Pericardium/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Animals , Electrocardiography , Patch-Clamp Techniques , Rats , Reactive Oxygen Species/metabolism , SevofluraneABSTRACT
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.
Subject(s)
Cardiotonic Agents/pharmacology , Methyl Ethers/pharmacology , Myocardial Reperfusion Injury/drug therapy , Ventricular Fibrillation/prevention & control , Animals , Cardiotonic Agents/therapeutic use , Heart/drug effects , Heart/physiopathology , Hemodynamics/drug effects , In Vitro Techniques , Male , Malondialdehyde/metabolism , Methyl Ethers/therapeutic use , Myocardial Reperfusion Injury/complications , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Sevoflurane , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/prevention & control , Ventricular Fibrillation/etiologyABSTRACT
Sevoflurane postconditioning is a potential clinical measure to protect myocardial. This experiment was designed to investigate the efficacy of sevoflurane postconditioning against ischemia-reperfusion injury. A total of 132 Japanese White Rabbits were enrolled into this study. They were underwent 15-, 30-, or 60-min left anterior descending coronary (LAD) artery occlusion, respectively. At the end of LAD artery occlusion, they randomly received a 5-min inhalation of air (control group), 1% sevoflurane (1% sev group), 2% sevoflurane (2% sev group), 4% sevoflurane (4% sev group) or an IV bolus injection of 5 mg/kg of NIM811 [a specific inhibitor of mitochondrial permeability transition pores (mPTP)]. Infarct size was determined after 2 h of reperfusion (triphenyltetrazolium chloride straining, percentage of risk area). The infarct sizes were significantly (P < 0.05) reduced after 15 min ischemia (5.5 ± 3.3%, 5.8 ± 3.6% vs. 20.3 ± 6.9% for 2% sev, 4% sev vs. control, respectively) and 30 min ischemia (23.5 ± 5.0%, 20.7 ± 5.9% vs. 50.9 ± 10.2%, for 2% sev, 4% sev vs. control, respectively; P < 0.05). However, it had no effect on infarct size after 60 min ischemia (64.1 ± 5.9%, 62.3 ± 7.6% vs. 72.7 ± 9.2% for 2% sev, 4% sev vs. control, respectively, P > 0.05).The efficacy of sevoflurane postconditioning gradually weakened with increasing ischemia duration and disappears after 60 min ischemia in rabbits in vivo.
Subject(s)
Cardiotonic Agents/pharmacology , Ischemic Postconditioning , Methyl Ethers/pharmacology , Myocardial Reperfusion Injury/prevention & control , Animals , Female , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Hemodynamics/drug effects , Male , Myocardial Infarction/blood , Myocardial Infarction/complications , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/complications , Myocardial Reperfusion Injury/physiopathology , Organ Size/drug effects , Rabbits , Risk Factors , Sevoflurane , Troponin/blood , Ventricular Function, Left/drug effectsABSTRACT
OBJECTIVE: To investigate the relationship between postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) after coronary artery bypass graft in Chinese population. METHODS: One hundred and seven patients who were referred for elective coronary artery bypass grafting (CABG) surgery were enrolled in this prospective cohort study. Baseline and perioperative variables as well as occurrence of postoperative complications were recorded. POD was diagnosed using the Confusion Assessment Method for the Intensive Care Unit twice daily during the first seven postoperative days. A neuropsychological test battery that included 7 tests with 9 subscales was administered at baseline and on the seventh day after surgery. POCD was defined using the same definition that was used in the ISPOCD1 study. RESULTS: The incidence of POD was 47.7% (51/107) while that of POCD was 55.3% (57/103). Multivariate Logistic regression analyses identified four independent risk factors of POD, i.e., increasing age (OR 1.174, 95% CI 1.085-1.269, P<0.001), preoperative history of diabetes mellitus (OR 4.224, 95% CI 1.543-11.563, P=0.005), occurrence of postoperative complications (OR 3.667, 95% CI 1.152-11.670, P=0.028), and prolonged duration of intensive care unit stay (OR 1.024, 95% CI 1.005-1.044, P=0.016). And two independent risk factors of POCD were identified, i.e., increasing age (OR 1.065, 95% CI 1.001-1.134, P=0.047) and prolonged duration of POD (OR 1.744, 95% CI 1.173-2.593, P=0.006). CONCLUSION: POD and POCD are common cognitive complications after CABG surgery in Chinese population. Prolonged duration of POD is an independent risk factor of the occurrence of POCD.
Subject(s)
Cognition Disorders/etiology , Coronary Artery Bypass/adverse effects , Delirium/etiology , Aged , China/epidemiology , Cognition Disorders/epidemiology , Delirium/epidemiology , Female , Humans , Logistic Models , Male , Middle Aged , Prevalence , Prospective Studies , Risk Factors , Time FactorsABSTRACT
OBJECTIVE: To summarize the anesthesia managements on 63 CAD patients undergoing 1-stop hybrid revascularization from July 2007 to June 2009 in Fuwai Hospital. METHODS: ECG, direct BP, SpO2, P(ET)CO2, CVP and body temperature were monitored during anesthesia. The management of intraoperative anesthesia should preferably use a small dosage of opioids with inhalation or intravenous anesthesia. At the same time, specific anticoagulation management was administered. RESULTS: The hemodynamics were stabilized. the time of tracheal intubation were shorter. 6 patients were immediate extubated in the operating room with application of fast-track technology. No patient died. CONCLUSIONS: Such minimally invasive surgery has little effect on the circulation. The difficulty of anesthetic management is smaller. Specific anticoagulation management is administered. Implementation of the Fast-track technology can demonstrate the further advantages in such surgery.
Subject(s)
Anesthesia/methods , Coronary Artery Disease/surgery , Myocardial Revascularization/methods , Aged , Anesthetics , Female , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Heart/drug effects , Methyl Ethers/therapeutic use , Reperfusion Injury/prevention & control , Anesthetics, Inhalation/therapeutic use , Animals , Apoptosis/drug effects , Male , Random Allocation , Rats , Rats, Sprague-Dawley , SevofluraneABSTRACT
OBJECTIVE: To evaluate the efficacy of one-stop hybrid coronary revascularization [simultaneous minimally invasive direct coronary artery bypass surgery (MIDCAB) and percutaneous coronary intervention (PCI) procedures performed in an enhanced (or called "hybrid") operative unit] for the treatment of unprotected left main coronary artery (ULMCA) disease. METHODS: From June 2007 to April 2009, 14 patients [13 male, mean age: (60.4 +/- 15.4) years] underwent the one-stop hybrid approach in the "hybrid" operating room. Proximal lesions were evidenced in 5 patients and distal or bifurcation lesions in 11 patients. MIDCAB procedure for grafting of the left intramammary artery (LIMA) with the left anterior descending (LAD) artery was first performed via lower partial ministernotomy on the beating heart, followed by PCI on the LMCA disease and non-LAD coronary lesions. RESULTS: Operation was successful in all patients underwent the one-stop hybrid procedure. LIMA grafts were used in all 14 patients and confirmed to be patent by angiography. A total of 25 non-LAD coronary lesions were treated by PCI and 29 stents (27 drug-eluting stents and 2 bare-mental stents) were implanted to 23 lesions and coronary angioplasty was performed in the remaining lesions. There was no death, perioperative myocardial infarction, stroke or repeat revascularization during the procedure and the follow-up period. All the patients remained free from angina during the 7.9 months (range 1 - 15 months) follow-up period. LIMA grafts and stents were patent in 5 patients at 1-year follow-up. CONCLUSIONS: Our initial experience demonstrates that one-stop hybrid coronary revascularization provides a reasonable, feasible and safe alternative for selected patients with LMCA diseases.
Subject(s)
Coronary Artery Disease/therapy , Myocardial Revascularization/methods , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary , Coronary Artery Bypass, Off-Pump , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
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.
Subject(s)
Glycogen Synthase Kinase 3/metabolism , Ischemic Postconditioning , Methyl Ethers/therapeutic use , Myocardium/enzymology , Proto-Oncogene Proteins c-akt/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/enzymology , Animals , Blotting, Western , Cytochromes c/metabolism , Enzyme Activation/drug effects , Glycogen Synthase Kinase 3 beta , Hemodynamics/drug effects , In Vitro Techniques , Male , Methyl Ethers/pharmacology , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Permeability Transition Pore , Myocardium/pathology , Phosphorylation/drug effects , Rats , Rats, Wistar , Reperfusion Injury/physiopathology , SevofluraneABSTRACT
INTRODUCTION: The pathophysiology of postoperative delirium remains poorly understood. The purpose of this study was to examine the relationship between serum cortisol level and occurrence of early postoperative delirium in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 243 patients undergoing elective CABG surgery were enrolled. Patients were examined twice daily during the first five postoperative days and postoperative delirium was diagnosed by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Blood samples were obtained between 7 a.m. and 8 a.m. on the first postoperative day and serum cortisol concentrations were then measured. Multivariate logistic regression analyses were performed to identify risk factors of postoperative delirium. RESULTS: Postoperative delirium occurred in 50.6% (123 of 243) of patients. High serum cortisol level was significantly associated with increased risk of postoperative delirium (OR 3.091, 95% CI 1.763-5.418, P < 0.001). Other independent risk factors of postoperative delirium included increasing age (OR 1.111, 95% CI 1.065-1.159, P < 0.001), history of diabetes mellitus (OR 1.905, 95% CI 1.001-3.622, P = 0.049), prolonged duration of surgery (OR 1.360, 95% CI 1.010-1.831, P = 0.043), and occurrence of complications within the first day after surgery (OR 2.485, 95% CI 1.184-5.214, P = 0.016). Patients who developed postoperative delirium had a higher incidence of postoperative complications and a prolonged duration of postoperative ICU and hospital stay. CONCLUSIONS: Delirium was a common complication after CABG surgery. High serum cortisol level was associated with increased risk of postoperative delirium. Patients who developed delirium had outcomes worse than those who did not.