Predictive factors of hemodynamic collapse after coronary artery bypass grafting: a case-control study.

OBJECTIVE: Sudden hemodynamic collapse after coronary artery bypass graft (CABG) surgery is a complication with high morbidity and mortality. The aim of this study was to explore factors possibly predictive of this major complication. DESIGN: Retrospective case-control study. SETTING: University hospital, department of cardiothoracic surgery. PARTICIPANTS: Between 1988 and 1999, of 8,807 CABG patients, a total of 76 (0.9%) suffered hemodynamic collapse after CABG surgery unrelated to pericardial tamponade or bleeding. Preoperatively matched patients (by age, sex, New York Heart Association classification, number of diseased vessels, left ventricular ejection fraction, and diabetes) served as a control group (n = 76). INTERVENTIONS: Patients with sudden cardiovascular collapse underwent emergency reopening of the sternotomy and open cardiac massage (OCM group). Several pre-, intra-, and postoperative variables were compared, and significant parameters in match-pair analysis were further tested with regression techniques. MEASUREMENTS AND MAIN RESULTS: Of the 76 OCMs, 57 (75%) occurred during the first 5 postoperative hours. In-hospital mortality was 46% (35 of 76) versus 0% in controls; 5-year survival was 49% versus 95%. In the OCM group, cardiopulmonary bypass (CPB) time was significantly prolonged (p = 0.0024), and cardiac index (p = 0.05) and the first acid-base values after CPB were lower (pH, p = 0.0057; BE, p = 0.0014). Postoperative myocardial ischemia appeared in 33% of patients in the OCM group and in 8% of controls (p < 0.0001). OCM-group patients more frequently required postoperative inotropic (epinephrine, p = 0.0002) and mechanical support (intra-aortic balloon pump, p = 0.005). Regression analysis revealed a correlation between cardiopulmonary resuscitation risk and low cardiac index, postoperative ischemia, and low pH level. CONCLUSION: Inadequate tissue perfusion, postoperative myocardial ischemia, and increased need for inotropic and mechanical support preceded hemodynamic collapse. Interventions to improve tissue perfusion and to prevent and treat myocardial ischemia may result in a more favorable outcome.

Recombinant hirudin enhances cardiac output and decreases systemic vascular resistance during reperfusion after cardiopulmonary bypass in a porcine model.

OBJECTIVE: Cardiopulmonary bypass and surgical stress are accompanied by a systemic inflammatory response and activation of coagulation. Thrombin forms fibrin and activates platelets and neutrophils. Consequently, disseminated microthrombosis might increase capillary vascular resistance and thus impair reperfusion. We hypothesized that recombinant hirudin, a direct inhibitor of thrombin, could attenuate coagulation and enhance microvascular flow during reperfusion. METHODS: Twenty pigs undergoing 60 minutes of aortic clamping and 75 minutes of normothermic perfusion were randomized in a blinded setting to receive an intravenous bolus of recombinant hirudin (10 mg, 0.4 mg/kg; n = 10) or placebo (n = 10) 15 minutes before aortic declamping and then continued with an intravenous 135-minute infusion of recombinant hirudin (3.75 mg/h, 0.15 mg/kg) or placebo. Thrombin-antithrombin complexes, activated clotting times, and several hemodynamic parameters were measured before cardiopulmonary bypass, after weaning from cardiopulmonary bypass, and at 30, 60, 90, and 120 minutes after aortic declamping. Intramucosal pH and Pco(2) were measured from the luminal surface of ileum simultaneously with arterial gas analysis at 30-minute intervals. RESULTS: Recombinant hirudin inhibited thrombin formation after aortic declamping; at 120 minutes, thrombin-antithrombin complexes levels (microg/L, mean +/- SD) were 75 +/- 21 and 29 +/- 44 (P <.001) for placebo and pigs receiving recombinant hirudin, respectively. When compared with the placebo group, pigs receiving recombinant hirudin showed significantly higher stroke volume, cardiac output, and lower systemic vascular resistance at 60 and 90 minutes after aortic declamping (P <.05). Based on arteriomucosal Pco(2) and pH differences, progressive worsening of intestinal microcirculatory perfusion occurred in the placebo group but not in the recombinant hirudin group. CONCLUSION: Infusion of thrombin inhibitor recombinant hirudin during reperfusion was associated with attenuated postischemia left ventricular dysfunction and decreased vascular resistance. Consequently microvascular flow was improved during ischemia-reperfusion injury. Control of thrombin formation during reperfusion may be a feasible approach to improve oxygen delivery to reperfused vascular beds.

N-acetylcysteine as an additive to crystalloid cardioplegia increased oxidative stress capacity in CABG patients.

OBJECTIVE: This prospective, randomized study was designed to assess the effects of N-acetylcysteine (NAC) in coronary artery bypass graft (CABG) patients. DESIGN: Thirty-five consenting CABG patients with normal myocardial function were randomly divided into control (C) patients (N = 20) who received crystalloid (Plegisol) cardioplegia, and NAC patients receiving NAC in a 0.04 mol/l solution (N = 15) in Plegisol. Simultaneous coronary sinus and aortic blood samples, and myocardial biopsies were taken 1, 5 and 10 min after declamping. Hemodynamics was measured invasively for 24 h. RESULTS: There were no adverse effects observed. The myocardial glutathione content was significantly better preserved (p = 0.0001) and myeloperoxidase activity was over two times lower in the NAC group than in the C group (p = 0.03). The trap capacity gradient between the aorta and the coronary sinus increased significantly during the first minute of reperfusion in the treatment group (p = 0.001) when compared with the C group. In the first minute after reperfusion there were more leukocytes sequestered in the coronary circulation (p = 0.04) in the C group. The invasive hemodynamic data did not differ significantly between the groups. The incidence of arrhythmias was equal. CONCLUSION: NAC increased tissue capacity against oxidative stress and decreased inflammatory response in CABG patients with normal ejection fraction.

Oxidative stress has a role in malignant transformation in Barrett's oesophagus.

Mechanisms underlying the development of oesophageal adenocarcinoma are poorly understood. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barrett's oesophagus, we measured myeloperoxidase activity, superoxide dismutase activity, glutathione content and total aromatic DNA adducts. Mucosal specimens came from 52 patients in 6 groups: symptomatic gastro-oesophageal reflux disease (GORD) without and with endoscopic oesophagitis, Barrett's epithelium without and with dysplasia, adenocarcinoma in the oesophagus and controls. In the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence, glutathione content was progressively lower and myeloperoxidase activity higher than in controls, plateauing at Barrett's epithelium without dysplasia. Only in Barrett's epithelium with dysplasia was SOD activity significantly increased. In all patient groups, DNA adduct levels were significantly higher than the control level. Though these levels between patient groups did not differ significantly, the level was highest in Barrett's epithelium without dysplasia and progressively lower in Barrett's with dysplasia and adenocarcinoma. Pooled data showed a negative correlation between glutathione content and DNA adducts (-0.28, p = 0.05). Simultaneous formation of DNA adducts, increased myeloperoxidase-related oxidative stress, decreased antioxidant capacity (glutathione content) and the negative correlation between glutathione content and DNA adducts in the GORD-oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus indicate a role in the pathogenesis and malignant transformation related to oxidative stress.

Increased DNA adducts in Barrett's esophagus and reflux-related esophageal malignancies.

BACKGROUND: DNA adduct formation can initiate carcinogenic processes. AIM: To examine the pre-malignant condition of Barrett's esophagus by measuring the DNA adducts. METHODS: DNA adducts were measured in the proximal and distal esophagus of patients with Barrett's esophagus (n = 9), patients with adenocarcinoma in the distal esophagus/esophagogastric junction (n = 28), and in control group of patients (n = 8) using the 32-P-postlabeling method. The average levels of DNA adducts are expressed as mean adducts/10(9) nucleotides + standard error of the mean. RESULTS. The average DNA adduct levels in the distal esophagus were significantly higher in both the Barrett's esophagus (24.5 +/- 7.9) and the adenocarcinoma (12.0 + 3.0) than in the control patients (0.1 +/- 0.08), P < 0.001. In the proximal esophagus, the DNA adduct levels were approximately equal in the Barrett's esophagus (7.0 +/- 1.0) and in the adenocarcinoma group (6.4 +/- 0.65). However, the levels in the proximal esophagus in both groups were significantly higher than in the control group (2.1 +/- 0.67), P < 0.05. CONCLUSIONS: Patients with Barrett's esophagus and patients with esophageal/esophagogastric junction adenocarcinoma had significantly more DNA adducts than the control group. These results support the current concept of the carcinogenic potential of chronic gastroesophageal reflux, and the pre-malignant condition of Barrett's esophagus.