IL-8, IL-6 and ICAM-1 in serum of paediatric patients undergoing cardiopulmonary bypass with and without cardiocirculatory arrest

BACKGROUND: The aim of the present study was to evaluate the systemic inflammatory response to CPB in paediatric patients undergoing surgical correction of congenital heart diseases. METHODS: Experimental design: comparative investigation. Setting: paediatric cardiology hospital Intervention: ICAM-1, IL-8, and IL-6 production were analysed before and during CPB, and after surgery in 9 paediatric patients, submitted to cardiocirculatory arrest (Group A); and in 11 without cardiocirculatory arrest (Group B). Measures: ICAM-1, IL-8, and IL-6 production were analysed from arterial samples before and during CPB, and after surgery. RESULTS: In group A vs group B a significant increase of IL-8 was detected during (297+/-250 vs 11+/-19 pg x ml(-1), p<0.001) and after (100+/-230 vs n.d. pg x ml(-1)) surgery and was correlated with the duration of operation (r=0.759; p=0.0001) and clamping time (r=0.738; p<0.05). After surgery in group A, IL-6 levels (35+/-43 pg x ml) were higher than those in group B (2+/-5 pg x ml), and a good correlation was observed between IL-6 and duration of aortic clamping (r=0.714; p=0.048), cardiac arrest, (r=0.714; p=0.048), and length of surgery (r=0.867; p=0.04). CONCLUSIONS: In children who underwent CPB with cardiocirculatory arrest cytokine production seems related to duration of operation and amplified by ischemia-reperfusion phenomena.     

Risk factors of stroke and delirium after off-pump coronary artery bypass surgery

Off-pump coronary artery bypass surgery (CABG) has not abolished the risk of postoperative stroke and delirium seen for on-pump CABG. Advanced arteriosclerotic changes are common in both on-pump and off-pump CABG. We sought to analyze if advanced arteriosclerotic changes are risk factors of stroke or transient ischemic attack (TIA), and delirium after off-pump CABG. Patients undergoing off-pump CABG between 2001 and 2005 were reviewed using medical records (n=685). Potential risk factors of postoperative stroke and delirium were identified from previous studies. Further, variables retrieved from carotid artery duplex scanning as indices of advanced arteriosclerosis, were examined. The incidences of postoperative stroke/TIA and delirium after off-pump CABG were 2.6% (n=18) and 16.4% (n=112), respectively. Carotid artery stenosis >50% was a significant risk factor of stroke or TIA (P=0.02) as well as delirium (P=0.04) after off-pump CABG. A history of atrial fibrillation (AF) (P=0.037) or diabetes mellitus (P=0.041) was a risk factors of postoperative stroke or TIA. In contrast, age over 75 years (P=0.006), creatinine >1.3 mg/dl (99 μmol/l) (P=0.011), a history of hypertension (P=0.001), past history of AF (P=0.024), and smoking (P=0.048) were significant risk factors of postoperative delirium.     

Cardioplegic arrest does not increase the risk of atrial fibrillation after coronary artery bypass surgery.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass grafting (CABG). It is a considerable source of morbidity, prolongs hospital stay and increases costs of treatment. Atrial cannulation, cardiopulmonary bypass and cardioplegic arrest have been suggested to play a role in the development of AF after CABG. The aim of this case-control study was to evaluate the role of cardiopulmonary bypass and cardioplegic arrest in the development of postoperative AF. METHODS: Data from 114 patients undergoing CABG without cardiopulmonary bypass and cardioplegic arrest (off-pump) between October, 1998 and December, 2002 were evaluated for the occurrence of postoperative AF. Each patient was individually matched by gender, age (+/-3 years), left ventricle ejection fraction (+/-5%), history of myocardial infarction, unstable angina, and beta-blocker medication with patients undergoing CABG with cardiopulmonary bypass and cardioplegic arrest (on-pump) during the same period. The data from off-pump and on-pump groups were compared. RESULTS: Off-pump and on-pump groups had similar preoperative characteristics. The number of distal anastomoses was lower in the off-pump (2.3+/-0.9) than in the on-pump (3.9+/-1.1, (P<0.001) group. However, the incidence of postoperative AF in the off-pump (36.8%) and the on-pump groups (36.0%) did not differ from each other. Old age was the only independent predictor of AF after CABG. CONCLUSIONS: Neither cardiopulmonary bypass nor cardioplegic arrest increases the risk of postoperative AF after CABG.     

Plasma soluble interleukin-2 receptor levels during and after upper abdominal surgery

Soluble interleukin-2 (IL-2) receptor (sIL-2R) is reported to be up-regulated in inflammatory disorders. Although sIL-2R may modulate perioperative inflammatory responses, it remains unclear whether upper abdominal surgery affects plasma sIL-2R levels. We evaluated the influence of major abdominal surgery on plasma sIL-2R levels. Ten patients scheduled for upper abdominal surgery received anaesthesia with isoflurane, nitrous oxide, and epidural block. Plasma sIL-2R and IL-6 levels were determined at pre-anaesthesia, 0, 2, and 4 hours during surgery, and on postoperative days 1 (POD1) and 3 (POD3). The plasma levels of sIL-2R decreased significantly and achieved their minimum value at 4 hours (677.0 +/- 125.3 pg/ml, P < 0.01 compared to pre-anaesthesia value; 924.5 +/- 178.8 pg/ml, 95% confidence interval = 122.2-550.4). The plasma sIL-2R levels increased on POD1 (1336.5 +/- 174.0 pg/ml) and POD3 (1629.0 +/- 262.8 pg/ml), and reached a level significantly higher than the baseline (P < 0.05 and P < 0.001, 95% confidence interval = 93.4-730.6 and 402.8-1006.2, respectively). The plasma sIL-2R levels on POD3 significantly correlated with the peak IL-6 levels (r = 0.67, P < 0.05). The plasma sIL-2R levels on POD3 correlated with the amount of intraoperative bleeding (r = 0.66, P < 0.05). In conclusion, we found that major abdominal surgery induces characteristic changes in plasma soluble IL-2 receptor levels.     

Off-pump CABG attenuates myocardial enzyme leakage but not postoperative brain natriuretic peptide secretion.

BACKGROUND: Off-pump coronary artery bypass surgery is considered to be less invasive compared with a conventional coronary artery bypass surgery, while objective assessment of its invasiveness has not been well established. The grade of invasiveness of off-pump CABG was evaluated by biochemical markers released from the myocardium. METHODS: Perioperative serial changes of myocardial enzyme leakage (creatine kinase-MB isoenzyme and troponin T) were evaluated in 217 patients who underwent coronary artery bypass surgery (28 off-pump CABG patients and 189 conventional CABG patients). Serial changes of atrial natriuretic peptide and brain natriuretic peptide secretion as markers of heart failure were also evaluated in 12 off-pump CABG patients and 49 conventional CABG patients. RESULTS: Myocardial enzyme leakage was significantly less in the off-pump CABG group, while increase of brain natriuretic peptides secretion were similar in both groups with its peak at the first postoperative day (246+/-46 pg/ml in the off-pump CABG group and 312+/-57 pg/dl in the conventional CABG group). CONCLUSIONS: Although off-pump CABG seems to be less invasive to the myocardial cells from the aspect of enzyme leakage, ischemic stress to the heart assessed by brain natriuretic peptide secretion was similar to that of conventional CABG. Careful monitoring and management throughout postoperative period is mandatory even in off-pump CABG procedure.     

Postoperative hyperthermia following off-pump versus on-pump coronary artery bypass surgery

OBJECTIVE: Hyperthermia is common in the first 24 hours following coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB). An inflammatory response to CPB is often implicated in the pathophysiology of this fever. Unlike CABG with CPB, the temperature pattern after off-pump CABG (OPCAB), where CPB is avoided, has not yet been described. The purpose of this study was to describe the postoperative temperature pattern following OPCAB and to compare it with that following on-pump cardiac surgery. DESIGN: Retrospective, observational study. SETTING: Tertiary care university hospital. PARTICIPANTS: Consenting patients undergoing CABG or OPCAB procedures. INTERVENTIONS: Observational. MEASUREMENTS AND MAIN RESULTS: Of the CABG patients, 89% had temperature elevations above 38 degrees C, versus 44% of the OPCAB patients (P = 0.04). Peak body temperature was higher in the on-pump patients (CABG 38.5 degrees C +/- 0.4 degrees C versus OPCAB 37.9 degrees C +/- 0.5 degrees C; P = 0.002), as was the area under the curve for temperatures greater than 38 degrees C (CABG 1.6 +/- 1.7 degrees C/hr versus OPCAB 0.4 +/- 1.2 degrees C/hr; P = 0.02). CONCLUSIONS: Off-pump CABG surgery patients experience less hyperthermia compared with on-pump CABG patients. The reasons for a lower incidence and severity of hyperthermia after OPCAB surgery are not known, but may be related to a reduced inflammatory response.     

S100 protein and its relation to cerebral microemboli in on-pump and off-pump coronary artery bypass surgery.

OBJECTIVES: S100 protein has been used as a marker for cerebral injury. Studies have reported lower levels in off-pump coronary artery surgery (CABG) compared to on-pump surgery. However, most of these are flawed as S100 from extracerebral sources was included (e.g. blood from cardiotomy suckers). Microemboli (high-intensity transient signals or HITS) during CABG have been implicated as a cause of postoperative neurocognitive dysfunction. The aim of this study was to compare the number of HITS during on-pump and off-pump CABG, measure S100 accurately by excluding extracerebral sources, and assess whether any changes in S100 were related to HITS. METHODS: Thirty-five patients admitted for CABG were randomised to on-pump (n=20) or off-pump (n=15) surgery. Bilateral transcranial Doppler ultrasonography was performed on the middle cerebral artery to detect HITS. S100 was measured preoperatively, at termination of bypass in on-pump surgery, at completion of anastomoses in off-pump surgery, and 48 h postoperatively. A cell saver was used instead of cardiotomy suction in the on-pump group in order to limit extracerebral contamination of the S100 assay. RESULTS: The number of HITS was 2016+/-1897 during on-pump and 16+/-21 during off-pump surgery (P<0.0001). In on-pump surgery S100 increased from 0.05+/-0.03 to 0.50+/-0.28 microg/l (P<0.0001) at termination of bypass. In off-pump surgery S100 increased from 0.08+/-0.05 to 0.35+/-0.20 microg/l (P<0.0001) at completion of anastomoses. The mean intraoperative S100 in the on-pump group was 1.6 times greater compared to that in the off-pump group (95% CI 0.88-2.8; P=0.01). There was no evidence of a relationship between S100 and HITS in both groups. By 48 h S100 decreased to 0.22+/-0.14 microg/l in the on-pump and 0.21+/-0.09 microg/l in the off-pump group (P<0.0001, compared to the preoperative value). CONCLUSIONS: We have demonstrated a significantly higher number of cerebral microemboli in patients undergoing on-pump compared to off-pump CABG. By limiting contamination from extracerebral sources, we have shown S100 beta levels during on-pump CABG one and a half times greater than that in off-pump, although this did not reach statistical significance. In addition, we have shown no correlation between S100 beta and the total microemboli count, possibly because of the small numbers in this study.     

Atrial fibrillation and plasma troponin I elevation after cardiac surgery: relation to inflammation-associated parameters

BACKGROUND: Recent studies have demonstrated correlation between inflammation to plasma troponin (cTnI) levels elevation and atrial fibrillation (AF) in noncardiac surgery settings. The goal of this prospective study was to examine the relation between inflammation associated parameters (IAPs) to post cardiac surgery cTnI elevation and AF. METHODS: A single post CABG cTnI measurement was assessed in 156 consecutive patients. Clinical, operative and postoperative data, IAPs (hypophosphatemia, preoperative statin treatment, immediate postoperative fever, and prolonged mechanical ventilation) and in-hospital AF episodes were prospectively recorded. RESULTS: Mean cTnI level was 14.4 +/- 12.4 ng/mL. In the two in-hospital deaths (1.2%) cTnI concentration was less than 12 ng/mL. Cardiac troponin-I levels were significantly higher in patients not preoperatively treated with statins (21.6 +/- 4.1 vs. 13.3 +/- 0.9, p = 0.05), in patients who needed intraoperative cardioversion (16.7 +/- 2.2 vs. 12.2 +/- 0.9, p = 0.07), in patients with postoperative hypophosphatemia (16.9 +/- 10.0 vs. 11.1 +/- 13.7, p = 0.04), postoperative fever (18.6 +/- 3.0 vs. 13.7 +/- 1.0, p = 0.07) and postoperative respiratory complications (23.9 +/- 4.3 vs. 13.5 +/- 1.0, p = 0.04). Step-wise logistic regression analysis revealed the following parameters as independently associated with elevated cTnI levels: preoperative statin treatment (CI 95%-15.9; -1.7, p = 0.02), intraoperative ventricular arrhythmia (CI 95%-0.7; 13.8, p = 0.08), hypophosphatemia (CI 95% 0.9; 8.6, p = 0.02), postoperative fever (CI 95% 0.9; 11.0, p = 0.02), and postoperative respiratory complications (CI 95% 0.1; 0.5, p = 0.01). Of the 156 patients, 50 (32.1%) had postoperative AF. The first episode of AF occurred between postoperative day 1 and 6 (mean-day 2). Mean duration of AF was 21.8 +/- 8.1 hours. Postoperative AF was significantly associated with age above 75 (50% vs. 29.4%, p = 0.01), hypertension (37% vs. 18%, p = 0.02), preoperative calcium channel blockers treatment (44% vs. 26%, p = 0.02), furosemide treatment (58% vs. 30%, p = 0.05), and preoperative left atrial diameter above 40 mm (56% vs. 29%, p = 0.01). Postoperatively, AF was significantly associated with postoperative renal failure (70% vs. 29%, p = 0.01), respiratory complications (61% vs. 29%, p = 0.02), and prolonged hospital stay (OR 1.1; CI 1.0-1.3; p < 0.05). No association was found between troponin levels and postoperative AF. Multivariable analysis found only left atrial enlargement and prolonged hospital stay independently associated with AF. CONCLUSIONS: A significant correlation between clinical IAPs and cTnI plasma level elevation was found after cardiac surgery. There was no correlation between these parameters and postoperative AF, and there was no correlation between postoperative plasma cTnI levels and the occurrence of AF. Preoperative treatment with statins may be beneficial in reducing postoperative inflammatory response but further study has to be carried out.     

冠心病患者围手术期炎症反应的研究

目的　探讨体外循环或非体外循环下冠状动脉搭桥和激光心肌打孔治疗冠心病时围手术期炎症因子变化的特点 ,为冠心病围手术期的临床治疗提供参考。　方法　测定 37例冠心病患者及 10例瓣膜病患者术前 ,搭桥或打孔前 ,主动脉开放时 (搭桥结束时或打孔后 )及术后 3、6、2 4h的血浆肿瘤坏死因子 (TNF α)、白介素 6 (IL 6 )、C反应蛋白 (CRP)的水平。　结果　术后患者血浆TNF α、IL 6、CRP水平均有一定程度升高 ,使用体外循环患者TNF α为 (4 10± 0 71)pg/ml,显著高于不使用者的 (1 34± 0 2 9)pg/ml,差异有显著性意义 (P <0 0 5 ) ;两者IL 6差异无显著性意义 (P >0 0 5 )。冠状动脉搭桥患者术后CRP为 (12 89± 0 2 9) μg/ml,高于瓣膜病患者的 (12 0± 0 31) μg/ml,差异有显著性意义 (P <0 0 5 )。　结论　冠心病患者 ,冠状动脉搭桥、激光打孔手术后 ,围手术期均有一定程度的炎症反应 ,体外循环者反应较重     

High Postoperative Interleukin-8 Levels Related to Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Surgery

BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered postoperative arrhythmic complication after coronary artery bypass graft (CABG). There is increasing evidence to support the influence of inflammation in the pathogenesis of AF. The aim of the present study was to investigate the relation of postoperative new AF and systemic inflammatory changes after CABG. METHODS: A total of 113 CABG patients were recruited in the present study. Holter data from 24-hour electrocardiography were collected from 1 day before the operation to postoperative day 2 (POD2). AF was registered as positive if any AF event occurred. Serum cytokine, including interleukin (IL)-6, IL-8, and IL-10 were analyzed before and after surgery. RESULTS: The overall incidences of postoperative AF and sustained AF were 36.3% and 31.9%, respectively. Patients with postoperative AF had longer respiratory treatment, intensive care unit treatment, and inotropic medication periods. Similar concentrations of serum IL-6 were found after surgery in patients with and without AF. The concentrations of serum IL-8 was significantly higher at 2 hours and on POD1 and POD2 in patients with postoperative AF. The concentration of serum IL-10 was significantly higher on POD1 in patients with postoperative AF. CONCLUSIONS: Postoperative AF in CABG patients is associated with a more complicated postoperative outcome. Higher concentrations of serum IL-8 in CABG patients with postoperative AF suggested that an influence of inflammation in the pathogenesis postoperative AF after open heart surgery.     

Endothelial apoptosis and circulating endothelial cells after bypass grafting with and without cardiopulmonary bypass.

OBJECTIVE: We compared profiles of the numbers of circulating endothelial cells (CEC) and the apoptosis-inducing capacity of serum samples on human endothelial cells (hEC) in on-pump and off-pump coronary artery bypass grafting (CABG) patients. METHODS: Blood samples from 30 patients undergoing CABG (randomly assigned to two groups: 15 patients off-pump and 15 on-pump (cardiopulmonary bypass, CPB)) were collected after induction of anesthesia (preoperatively), at weaning from CPB/end of bypass grafting (0 h), and 1, 6, 12, 24, and 48 h afterwards. CEC were isolated with immunomagnetic anti-CD146-coated Dynabeads, and counted in a Nageotte chamber. The apoptosis-inducing activity of serum samples on hEC was examined by a tissue culture assay system. Apoptotic and normal cells were identified using phase contrast/fluorescence microscopy after DNA dye staining. RESULTS: CEC numbers and proportions of apoptotic hEC were significantly elevated during and after surgery in both groups (p<0.01). Compared with the on-pump group, CEC and proportions of apoptotic hEC were significantly lower (p=0.04 and p=0.03, respectively) in patients having CABG performed off-pump. Starting at comparable baseline levels, the mean CEC-number was highest at 6h postoperatively with 81.9 ml(-1) (range, 44-141) for on-pump patients and 63.3 ml(-1) (range, 48-105) for off-pump patients. hEC apoptosis peaked also at T4: 16.5+/-2.8% versus 11.3+/-2.2%. In both groups, CEC numbers and proportions of endothelial apoptosis were still elevated at 48 h after surgery. CONCLUSION: The number of circulating endothelial cells and apoptotic endothelial cell death are markers of endothelial activation and damage during CABG. This study provides evidence that CABG with the use of CPB in comparison to OPCAB surgery is associated with a significantly more pronounced endothelial response in the immediate postoperative period.     

Off-pump coronary artery bypass

OBJECTIVES: Off-pump coronary artery bypass grafting (CABG) on the beating heart has become popular procedure in cardiac surgery and its initial results appeared favorable. We report our early and mid-term results of off-pump CABG performed at Shin-Tokyo Hospital. METHODS: Medical records of patients undergoing off-pump or conventional on-pump CABG from September 1, 1996, to August 31, 1999 were retrospectively reviewed. Patients underwent off-pump CABG were further classified into 2 groups; MIDCAB (Off-pump CABG for single vessel revascularization via a small skin incision) and OPCAB (off-pump CABG mainly approached via midline sternotomy) group. Their preoperative, perioperative, and follow-up data were collected and analyzed. RESULTS: Among a total of 995 cases of CABG, 194 cases were off-pump CABG (male/female 142/52, mean age 66.9). The mean number of distal anastomoses in off-pump CABG was 1.9 +/- 0.9 (1.0 +/- 0.0 in MIDCAB and 2.3 +/- 0.7 in OPCAB), which was significantly fewer than in on-pump CABG (3.6 +/- 1.1), with p < 0.0001. Intubation time (5.3 +/- 5.7 hours in off-pump CABG vs 13.1 +/- 24.2 hours in on-pump CABG), ICU stay (1.7 +/- 1.1 vs 3.2 +/- 3.0 days), and postoperative hospital stay (14.0 +/- 7.9 vs 18.1 +/- 12.1 days) in off-pump CABG were significantly shorter than in on-pump CABG (p < 0.0001). In the off-pump CABG group, there were no in-hospital deaths and 14 major complications, fewer than in on-pump CABG (8 hospital deaths and 114 major complications). Postoperative angiography before hospital discharge was conducted in 80 patients (41.2%) and showed 2 occlusions, giving a graft patency rate of 98.6% in the off-pump group. During follow-up (0.9 +/- 0.6 year) period, there were 5 non-cardiac deaths and 20 cardiac events in the off-pump group. The actuarial survival rate at 36 months was 94.6% for off-pump CABG, showing no significant difference from the rate for conventional CABG patients (95.2% at 36 month, p = NS) The event-free rate was 84.0% at 36 months in off-pump CABG patients; however, which was less favorable than on-pump CABG patients (88.0% at 36 months, p < 0.05). CONCLUSIONS: Both in-hospital and mid-term results for off-pump CABG patients were acceptable. Isolated CABG can thus be safely performed without cardiopulmonary bypass. Advances in coronary stabilization have contributed to these improved results. The observed long-term cardiac events may be related to incomplete revascularization.     

Comparison of minimally invasive closed circuit extracorporeal circulation with conventional cardiopulmonary bypass and with off-pump technique in CABG patients: selected parameters of coagulation and inflammatory system.

OBJECTIVE: Closed circuit extracorporeal circulation (CCECC) has been developed to reduce deleterious effects of standard cardiopulmonary bypass (CPB). This study compares the effects of CCECC (CORx system), CPB, and off-pump coronary artery bypass grafting (OPCAB) on red blood cell damage, coagulation activation, fibrinolysis and cytokine expression. METHODS: Thirty patients underwent coronary artery bypass grafting (CABG). Twenty of them were randomized into two groups: CCECC (n = 10), CPB (n = 10). While not randomized, OPCAB (n = 10) served as a separate reference group. CCECC and CPB patients received cardioplegic arrest. Interleukin 6 (IL-6), free hemoglobin (fHb), von Willebrand factor activity (vWf), thrombin-antithrombin-III-complex (TATc), prothrombin fragment 1.2 (F 1+2) and plasmin-antiplasmin complex (PAPc) were assessed preoperatively, perioperatively and 24 h postoperatively. RESULTS: CCECC showed significantly lower red blood cell damage than CPB (fHb: CCECC, 7.1+/- 5.7 micromol/l; CPB, 16.8+/-11.4 micromol/l; P = 0.025; OPCAB, 3.4+/-1.1 micromol/l). Perioperatively, CCECC exhibited significantly lower activation of coagulation and fibrinolysis than CPB, but did not differ from OPCAB (vWf: CCECC, 133+/-52%; CPB, 241+/-128%; P = 0.052; OPCAB, 153+/-58%; TATc: CCECC, 4.7+/-0.9 ng/ml; CPB, 31.1+/-15.8 ng/ml; P < 0.001; OPCAB, 2.4+/-0.6 ng/ml; PAPc: CCECC, 214+/-30 ng/ml; CPB, 897+/-367 ng/ml; P < 0.001; OPCAB, 253+/-98 ng/ml). In contrast, fibrinolysis markers and IL-6 were markedly increased in CCECC postoperatively (PAPc: CCECC, 458+/-98 ng/ml; CPB, 159+/-128 ng/ml; P < 0.001; OPCAB, 262+/-174 ng/ml; IL-6: CCECC, 123.4+/-49.8 pg/dl; CPB, 18.8+/-13.1 pg/dl; P < 0.001; OPCAB, 31.6+/-26.2 pg/dl). CONCLUSIONS: CCECC for CABG is associated with a significant reduction of red blood cell damage and activation of coagulation cascades similar to OPCAB when compared with conventional CPB while a delayed fibrinolytic and inflammatory activity was observed. These findings require further investigation to verify the promising concept of CCECC.     

Endothelial cell dysfunction after coronary artery bypass grafting with extracorporeal circulation in patients with type 2 diabetes mellitus.

OBJECTIVE: Type 2 diabetes mellitus is a well-known risk factor in patients with severe coronary artery disease undergoing coronary artery bypass grafting (CABG). The aim of the study was to analyze the endothelial dysfunction in these patients by evaluating postoperative soluble inflammatory cytokines. METHODS: Patients undergoing CABG without (n=15, group A) and with (n=14, group B) diabetes mellitus were analyzed for their release of E-selectin, interleukin-6 (IL-6), and tumor necrosis factor (TNF) up to 3 days postoperatively. A pharmacokinetic quantitative kinetic evaluation (Kinetica 2000) of maximum concentrations (c(max)), time to reach c(max) (t(max)), area under the curve (AUC(0-inf)), and terminal elimination half time (t(1/2)) was performed using a non-compartmental model. RESULTS: There was no difference in preoperative plasma concentrations of the cytokines and in the postoperative kinetic analyses of TNF when comparing both groups. However, the release of IL-6 was restricted with c(max) of 1055+/-543 pg/ml for group B versus 2112+/-1532 pg/ml for group A (p< or =0.05), paralleled by a decrease in the absolute amount (AUC(0-inf)) of IL-6. The t(1/2) remained unaffected (13.9+/-6.6h and 12.7+/-4.6h, respectively). The AUC(0-inf) of E-selectin decreased by a factor of 1.7 (p< or =0.05) with unchanged c(max) but reduced t(1/2) (12.9+/-10h for group B vs 33.1+/-20.4h for group A; p< or =0.01) referring to an augmented endothelial uptake and degradation of E-selectin. CONCLUSIONS: CABG with extracorporeal circulation could be used to verify a specific endothelial dysfunction in diabetic patients characterized by an impaired release of IL-6 and an increased turnover of E-selectin.     

Urgent off-pump coronary artery bypass grafting

OBJECTIVES: The use of off-pump coronary artery bypass grafting (CABG) has become widespread, since it has proven less invasive and to promote early recovery. In this study, we investigated the efficacy of off-pump CABG in patients in the evolving phase of acute myocardial infarction. METHODS: Retrospective chart review was carried out for patients undergoing urgent isolated off-pump and on-pump CABG at Shin-Tokyo Hospital Group between January 1991 and June 2001. The patients' demographic, operative data, and postoperative results were collected. RESULTS: The off-pump group consisted of 19 males and 11 females with a mean age of 72.0 years and the on-pump group of 91 males and 38 females with a mean age of 64.3 years. Preoperative use of intraaortic balloon pumping and preoperative shock was more frequently observed in the on-pump group. The mean number of distal anastomoses was 3.1 +/- 0.9 in the off-pump group and 3.2 +/- 1.1 in the on-pump group (p = NS). Intubation time (18.5 vs 32.9 hours), ICU stay (3.4 vs 4.9 days), and postoperative stay (13.5 vs 24.3 days) were significantly shorter in the off-pump group than in the on-pump group (P < 0.05). The frequency of the major complications was significantly lower in the off-pump group (9/30, 30%) than the on-pump group (65/129, 50.4%), especially for postoperative low output syndrome (p < 0.05). Multivariate analysis demonstrated a significant reduction in the recovery period by use of off-pump CABG. Early follow-up results were similar between the two groups, in terms of late cardiac events and survival. CONCLUSION: Urgent off-pump CABG is safe and provides early recovery, provided that the patient's intraoperative hemodynamics are taken into account.     

Off-pump coronary artery bypass grafting for patients with three-vessel disease

BACKGROUND: Off-pump coronary artery bypass grafting (CABG) has been performed since 1996 in our institute, and its application has recently been expanded to patients with three-vessel disease. A study was performed to clarify the benefit of off-pump CABG for patients with three-vessel disease. METHODS: Between June 1, 1991 and September 30, 2001, a total of 1089 patients with three-vessel disease (832 men and 257 women; mean age, 64.0 +/- 9.1 years) underwent on-pump CABG. After 1997, a total of 310 patients with three-vessel disease (223 men and 87 women; mean age, 68.8 +/- 8.6 years) underwent off-pump CABG. Data of the historical cohort of on-pump CABG and the concurrent cohort of off-pump CABG were analyzed retrospectively. RESULTS: The 2 groups were age and gender matched. Significant comorbidities were more often observed in the off-pump group than in the on-pump group. The mean number of bypass grafts in the off-pump versus on-pump CABG was 3.3 vs 3.7, P <.0001. The mean intubation period, intensive care unit stay, and postoperative hospital stay were 7.9 vs 11.7 hours, 2.2 vs 3.0 days, and 14.5 vs 17.5 days, respectively (P <.0001). In-hospital mortality rate (0.6% vs 1.2%, respectively) and morbidity rates (10.3% vs 12.9%, respectively) were not significantly different. After surgery, calculated event-free rates at 2 years were 93.3% vs 91.9%, respectively; P = not significant. CONCLUSIONS: In patients with multivessel disease, off-pump CABG provided early recovery, and its complication rates and early follow-up results were equivalent to on-pump CABG.     

Nitric oxide expression by interleukin-10 in the endoscopic and open methods of vein harvesting in coronary artery bypass surgery.

OBJECTIVE: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that suppresses lymphocyte functions, regulates production of proinflammatory cytokines, and suppresses nitric oxide production by activated macrophages. We examined IL-10 expression and its value as a surrogate index for nitric oxide (NO) production in endothelial cultures obtained from saphenous vein samples. METHODS: Using 2 different techniques (the open and endoscopic), we harvested samples of human saphenous veins from 90 randomly selected patients undergoing coronary artery bypass surgery (CABG). Endothelial cells collected from the vein samples retrieved through both techniques were cultured for 72 hours. Using a solid phase enzyme linked-immuno-sorbent assay (ELISA), we analyzed pre- and postoperative sera, in addition to the supernatants from the cultures, for IL-10. RESULTS: Mean preoperative levels of IL-10 (0.09 +/- 0.04 pg/mL) did not differ significantly from that for postoperative sera (0.14 +/- 0.17 pg/mL) (P = 0.54). Mean IL-10 levels for endothelial cell culture supernatants did not differ significantly between the endoscopic (0.32 +/- 0.39 pg/mL) and the open method (0.46 +/- 0.80 pg/mL) (P= 0.30). CONCLUSION: Our findings indicate that endoscopic and open saphenectomies are technically comparable with respect to their effects on IL-10 release during saphenous vein harvesting for CABG. We recommend the endoscopic method for its low morbidity and earlier hospital discharge.     

Cardiac interleukin-6 release and myocardial recovery after aortic crossclamping. Crystalloid versus blood cardioplegia

BACKGROUND: Pro-inflammatory cytokines may play an important role in patient response to cardiopulmonary bypass (CPB). Since the myocardium is proposed to be a major source of cytokines, we studied the influence of the cardiolpegia type on interleukin-6 release and early myocardial recovery. METHODS: Experimental design: prospective, randomized study. Setting: university hospital, operative and intensive care. Patients: 20 consecutive patients (3 females) scheduled for elective coronary artery bypass grafting (CABG), mean age 62.8+/-5 years, history of myocardial infarction 11/20, left ventricular ejection fraction 62.9+/-15%. Interventions: patients were operated on using randomly either cold blood cardioplegia (B, n = 10) or cold crystalloid cardioplegia (C, n = 10). Measures: plasma levels of interleukin-6 (IL-6) were measured prior to CPB, after aortic declamping, after CPB, 1 hour, 6 hours and 12 hours postoperatively. RESULTS: Groups were comparable with respect to demographic data, left ventricular function, number of grafts, CPB and aortic crossclamp time. Group B patients demonstrated significant lower IL-6 levels after 1 hour (210+/-108 vs. 578+/-443 pg/ml), 6 hours (204+/-91 vs. 1210+/-671 pg/ml) and 12 hours (174+/-97 vs. 971+/-623 pg/ml). Post-CPB cardiac index was superior in group B (3.9+/-0.3 vs. 3.2+/-0.3 l/min/m2, p<0.05) with similar doses of inotropes. Group B patients could earlier be weaned off respirator (10+/-4 vs. 13+/-4 hours, p<0.05) and showed minor blood loss (635+/-211 vs. 918+/-347 ml, p<0.05). CONCLUSIONS: Inflammatory response to CPB is associated with delayed myocardial recovery. The use of blood cardioplegia may attenuate inflammatory reactions.     

Postoperative atrial fibrillation: a comparison of off-pump coronary artery bypass surgery and conventional coronary artery bypass graft surgery

OBJECTIVE: To compare the incidence and pattern of onset of postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass graft (CABG) surgery with and without cardiopulmonary bypass (CPB). DESIGN: Retrospective, cohort-controlled study. SETTING: University hospital and tertiary referral center. PARTICIPANTS: A group of 108 consecutive patients who underwent primary off-pump coronary artery bypass (OP-CAB) surgery and a control group of 100 patients who underwent CABG surgery with CPB. All patients underwent surgery between January and September 1999. INTERVENTIONS: Patients in the OP-CAB surgery group were operated on by either of 2 surgeons. The CABG surgery group was drawn from the general pool of patients operated on by 1 of 10 surgeons. All patients underwent median sternotomy and received standard anesthesia and intensive care unit management for this institution. MEASUREMENTS AND MAIN RESULTS: Data from 99 OP-CAB surgery patients (data incomplete in 9 patients) were compared with data from 100 CABG surgery patients. General demographics were similar except the CABG surgery group received a higher mean number of distal anastomoses (3.3 v 3.0; p = 0.028) The incidence of AF was similar in both groups (OP-CAB surgery, 25% v CABG surgery, 18%; p = 0.228). The peak incidence of AF was postoperative day 2 in both groups. The median hospital length of stay was increased in patients developing AF. CONCLUSION: Avoiding CPB does not seem to reduce the incidence of postoperative AF in CABG surgery. The similar time distribution of onset of AF in OP-CAB surgery patients and CABG surgery patients may point toward a common cause.     

Beating heart versus conventional single-vessel reoperative coronary artery bypass

BACKGROUND: Reoperative (redo) coronary artery bypass grafting (CABG) with cardiopulmonary bypass (on-pump) is associated with a higher morbidity and mortality than first-time CABG. It is unknown, however, whether CABG without cardiopulmonary bypass (off-pump) may yield an improved clinical outcome over conventional on-pump redo CABG. METHODS: We compared the perioperative outcomes of patients with single-vessel disease who underwent on-pump (n = 41) versus off-pump (n = 91) redo CABG between April 1992 and July 1999. The two groups were similar with respect to baseline characteristics and risk stratification: mean Parsonnet scores were 26 +/- 9 for on-pump versus 24 +/- 8 for off-pump patients (p = nonsignificant). RESULTS: On-pump redo patients had a higher rate of postoperative transfusions (58% on-pump versus 27% off-pump, p = 0.001), prolonged ventilatory support (17% on-pump versus 4% off-pump, p = 0.03), and a higher rate of postoperative atrial fibrillation (29% on-pump versus 14% off-pump, p = 0.04). On-pump redo CABG was also associated with prolonged postoperative length of stay (8 +/- 4 days on-pump versus 5 +/- 2 days off-pump, p < 0.001). In-hospital mortality was significantly higher in on-pump than in off-pump patients (10% versus 1%, p = 0.03). CONCLUSIONS: Single-vessel off-pump redo CABG can be performed safely with a lower operative morbidity and mortality than on-pump CABG and an abbreviated hospital stay compared with conventional on-pump redo CABG.