Arterial end-to-side grafting in coronary artery bypass grafting: the Tector procedure

Background. The current treatment of choice in patients with three-vessel coronary disease is coronary artery bypass grafting. The use of the left internal mammary artery in bypass grafting has shown superior long-term outcomes compared with venous grafting. In our study we assess the safety and feasibility of all-arterial coronary artery bypass graft surgery using the procedure as described by Tector et al. in 2001.Methods. Between June 2001 and February 2007, we studied 133 patients eligible for non-emergency surgical revascularisation. Primary endpoints were death or re-infarction within a 30-day period. Secondary endpoints were the need for emergency coronary surgery, angioplasty and mediastinitis. Long-term follow-up had a mean duration of 33 months postoperatively.Results. All 133 patients were successfully revascularised, 98% with the off-pump technique. In 93% of the patients (n=124) full arterial grafting was achieved using both internal mammary arteries. Thirty-day mortality was 1.5% (n=2), ten re-thoracotomies were performed, one myocardial infarction and one case of mediastinitis were reported. In the next four years six additional patients died. Most of these deaths were due to non-cardiovascular causes. Two patients required angioplasty because of distal bypass graft failure and one for new native coronary artery disease. Conclusion. All-arterial bypass grafting using both internal mammary arteries with the technique as described by Tector is safe and feasible without excess deep sternal wound infections. Late major adverse cardiac events are rare and due to distal graft dysfunction, which can be treated by percutaneous coronary intervention. (Neth Heart J 2010;18:7-11.)     

Estimation of hydroxyl radical generation by salicylate hydroxylation method in kidney of mice exposed to ferric nitrilotriacetate and potassium bromate

Hydroxyl radical (·OH) generation in the kidney of mice treated with ferric nitrilotriacetate (Fe-NTA) or potassium bromate (KBrO₃) in vivo was estimated by the salicylate hydroxylation method, using the optimal experimental conditions we recently reported. Induction of DNA lesions and lipid peroxidation in the kidney by these nephrotoxic compounds was also examined. The salicylate hydroxylation method revealed significant increases in the ·OH generation after injection of Fe-NTA or KBrO₃ in the kidneys. A significant increase in 8-hydroxy-2'-deoxyguanosine in nuclei of the kidney was detected only in the KBrO₃ treated mice, while the comet assay showed that the Fe-NTA and KBrO₃ treatments both resulted in significant increases in DNA breakage in the kidney. With respect to lipid peroxidation, the Fe-NTA treatment enhanced lipid peroxidation and ESR signals of the alkylperoxy radical adduct. These DNA breaks and lipid peroxidation mediated by ·OH were diminished by pre-treatment with salicylate in vivo. These results clearly demonstrated the usefulness of the salicylate hydroxylation method as well as the comet assay in estimating the involvement of ·OH generation in cellular injury induced by chemicals in vivo.     

Assessment of oxidative stress in coronary artery bypass surgery: comparison between the global index OXY-SCORE and individual biomarkers

The performances of the OXY-SCORE, a summary index of oxidative stress, and of its individual components (plasma malondialdehyde (MDA), oxidized and reduced glutathione, individual antioxidant capacity, α- and γ-tocopherol and urinary isoprostanes) were assessed in 47 patients undergoing coronary surgery, randomly assigned to cardiopulmonary bypass (CPB) or off-pump procedure (OPCAB) associated with less oxidative stress. The ability of the OXY-SCORE to classify correctly the patients was high (area under the ROC curve 0.90). Only free MDA showed a similar performance, but it was insensitive to the minor variations of the oxidative balance in the OPCAB group.     

80岁以上老年人冠状动脉旁路移植术合并瓣膜置换手术的临床分析

目的：总结老年患者行冠状动脉旁路移植术（CABG）合并瓣膜置换（VR）手术的特点及经验。方法：上海交通大学附属第一人民医院心血管外科2001年11月至2010年3月对60例年龄大于80的患者施行冠状动脉搭桥＋瓣膜置换手术,男33例,女27例。年龄80-87岁,平均年龄（83.77±2.45）岁。均为冠心病合并瓣膜病变患者。其中36例患者行冠状动脉旁路移植＋二尖瓣置换手术,15例患者行冠状动脉旁路移植＋主动脉瓣置换手术,9例患者行冠状动脉旁路移植＋双瓣置换手术,同时8例患者行三尖瓣成形手术,3例患者行射频消融手术,1例升主动开成形术。置换生物瓣膜者51例,置换机械瓣膜者9例。CABG平均搭桥（2.13±0.75）根,搭桥材料为左乳内动脉与大隐静脉。结果：全组早期死亡9例（15%）,1例死于术后出血,1例死于多器官功能衰竭,7例死于术后心衰。早期生存51例（85%）,出现术后并发症10例,其中2例发生胸腔积液,1例心包填塞,3例肺部感染,1例心房扑动后发生室颤,3例二次开胸止血。给予相应对症治疗后痊愈出院。门诊随访49例,随访时间1～60个月,心功能I级2例、Ⅱ级29例、Ⅲ级18例、Ⅳ级0例（NYHA分级）。结论：对老年患者行冠脉搭桥＋瓣膜置换手术,只要掌握手术适应证,充分作好术前准备、术中及术后处理,手术治疗可以取得良好效果。     

Predictors of postoperative atrial fibrillation after coronary artery bypass graft surgery

Objectives

The present study was aimed to identify the preoperative, intraoperative, and postoperative predictors of AF in a pure cohort of the patients with coronary artery disease who underwent CABG surgery.

Methods

Between November 2005 and May 2006, 302 consecutive patients were included in this prospective study. All the relevant clinical, electrocardiographic, echocardiographic, and laboratory data were gathered in the included patients and they were also monitored for development of post-CABG AF.

Results

Postoperative AF occurred in 46 (15%) of patients. By univariate analysis, older age, P-wave abnormality in ECG, presence of mitral regurgitation, larger left atrium (LA), left main coronary artery involvement, failure to graft right coronary artery (RCA), and adrenergic use in ICU were significantly associated with occurrence of post-CABG AF (all P< 0.05). However, in the logistic regression model, age (OR: 1.067, 95%CI: 1.02-1.116, P=0.005), LA dimension (OR: 1.102, 95%CI: 1.017-1.1936, P=0.017), P-wave morphology (OR: 12.07, 95%CI: 3.35-48.22, P=0.0001), failure to graft RCA (OR: 3.57, 95%CI: 1.20-10.64, P=0.022), and postoperative adrenergic use (OR: 0.35, 95%CI: 0.13-0.93, P=0.036) remained independently predictive of postoperative AF.

Conclusion

The present study suggested that age, P-wave morphology, LA dimension, failure to graft right coronary artery, and postoperative adrenergic use were independent predictors of post-CABG AF. Therefore, clinical data, ECG and echocardiography may be useful in preoperative risk stratification of the surgical patients for the occurrence of post-CABG AF.     

Exercise through a cardiac rehabilitation program attenuates oxidative stress in patients submitted to coronary artery bypass grafting*

Background: Cardiovascular disease is the main cause of morbidity and mortality in the world and oxidative stress has been implicated in the pathogenesis. Cardiac rehabilitation in patients with coronary artery disease submitted to coronary artery bypass grafting may prevent cardiovascular events probably through the attenuation of oxidative stress. The aim of this study was to evaluate the benefits of a cardiac rehabilitation program in the control of the systemic oxidative stress.

Methods: The studied population consisted of 40 patients, with chronic stable coronary artery disease submitted to coronary artery bypass grafting, who attended a cardiac rehabilitation program. Biomarkers of oxidative stress were evaluated in the blood of these patients at different moments.

Results: After the onset of cardiac rehabilitation, there was a significant and progressive decrease in thiobarbituric acid reactive substances levels and protein carbonyls, an initial increase and subsequent decrease in superoxide dismutase, catalase and glutathione peroxidase activities. Also, a progressive increase of uric acid, while ferric reducing antioxidant power levels increased only at the end of the cardiac rehabilitation and a tendency to increase of glutathione contents.

Conclusions: The results suggest that regular exercise through a cardiac rehabilitation program can attenuate oxidative stress in chronic coronary artery disease patients submitted to coronary artery bypass grafting.     

Protective effects of nicaraven,a new hydroxyl radical scavenger,on the endothelial dysfunction after exposure of pig coronary artery to hydroxyl radicals

Recently, we have reported that a new synthetic compound, 1,2bis(nicotinamido)-propane (nicaraven), improved cardiac function following preservation and reperfusion. In this study, we investigated the efficacy of nicaraven as a radical scavenger by using an in vitro model of oxidative stress, to clarify mechanisms of the protective effect of this new compound on reperfusion injury in rat heart. Ring segments of epicardial right coronary arteries (RCA) of pig were suspended in organ chambers and exposed to hydroxyl radicals (·OH), generated (by two different systems ) by 0.28 mM FeSO₄/0.28 mM H₂O₂ and DHF/Fe³⁺-ADP (2.4 mM, 43 nM, and 1.56 uM, respectively) to the bathing solution for 60 min. Prior exposure of the coronary arteries to ·OH significantly produced right-ward shift of the dose-response curves of the bradykinin-induced endothelium-dependent relaxations (an increase in the ED₅₀ value for bradykinin by 4.37 and 1.98 times than control in two different ·OH generating systems, respectively), but did not affect the maximum relaxation responses. The presence of nicaraven (10^-4 and 10^-5 M) in the ·OH generating system, shifted the dose-response curves to bradykinin to the control level, suggesting a significant hydroxyl radical scavenging effect of the drug. These results indicate that nicaraven, a new hydroxyl radical scavenger, exhibits a protective effect on hydroxyl radicalinduced endothelial dysfunctions of pig coronary artery.     

Striatal dopamine level contributes to hydroxyl radical generation and subsequent neurodegeneration in the striatum in 3-nitropropionic acid-induced Huntington's disease in rats

We tested the hypothesis that dopamine contributes significantly to the hydroxyl radical (OH)-induced striatal neurotoxicity caused by 3-nitropropionic acid (3-NP) in a rat model of Huntington's disease. Dopamine (10–100 μM) or 3-NP (10–1000 μM) individually caused a significant increase in the generation of hydroxyl radical (OH) in the mitochondria, which was synergistically enhanced when the lowest dose of the neurotoxin (10 μM) and dopamine (100 μM) were present together. Similarly, systemic administration of l-DOPA (100–250 mg/kg) and a low dose of 3-NP (10 mg/kg) potentiated OH generation in the striatum, and the rats exhibited significant decrease in stride length, a direct indication of neuropathology. The pathology was also evident in striatal sections subjected to NeuN immunohistochemistry. The significant changes in stride length, the production of striatal OH and neuropathological features due to administration of a toxic dose of 3-NP (20 mg/kg) were significantly attenuated by treating the rats with tyrosine hydroxylase inhibitor α-methyl-p-tyrosine prior to 3-NP administration. These results strongly implicate a major contributory role of striatal dopamine in increased generation of OH, which leads to striatal neurodegeneration and accompanied behavioral changes, in 3-NP model of Huntington's disease.     

Long-term outcomes of isolated aortic valve replacement and concomitant AVR and coronary artery bypass grafting

Background

It is well established that concomitant aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) has a higher operative mortality rate than isolated AVR. However, studies report conflicting results on the long-term mortality. The aim of this prospective study was to explore and compare the outcomes and risk factors of isolated AVR and concomitant AVR and CABG in a consecutive Dutch patient population.

Methods

From January 2001 through January 2010, 332 consecutive patients underwent AVR with or without CABG at a single institution (197 isolated AVR and 135 concomitant AVR and CABG). A multivariate Cox proportional hazard analysis was performed to determine the independent risk factors for long-term mortality after aortic valve replacement.

Results

All 332 consecutive, referred patients who underwent aortic valve surgery were followed for up to 10 years. Median follow-up length was 48 months. The population had a median age of 73 years (IQR 65–78) and predominantly consisted of males (62%). Patients in the combined AVR and CABG group were older, had worse cardiac risk profiles and had worse preoperative cardiac statuses than those receiving isolated AVR. Five-year survival was 85% in AVR and 73% in AVR-CABG (p-value 0.012). Independent risk factors for mortality were higher creatinine values, previous CABG and increasing age.

Conclusion

Unselected, consecutive patients who underwent aortic valve replacement surgery and who received concomitant bypass surgery between 2001–2010 had higher 5-year mortality than their counterparts without CABG. Prior CABG, renal function, age but not concomitant CABG remained independently associated with increased mortality. Finally, the observed mortality rate in this consecutive patient group compared favourably with preoperative risk assessment using the EuroSCORE.     

Oxidative status and reduced glutathione levels in premature coronary artery disease and coronary artery disease

Identifying patients at risk of developing premature coronary artery disease (PCAD) which occurs at age below 45 years old and constitutes approximately 7–10% of coronary artery disease (CAD) worldwide remains a problem. Oxidative stress has been proposed as a crucial step in the early development of PCAD. This study was conducted to determine the oxidative status of PCAD in comparison to CAD patients. PCAD (<45 years old) and CAD (>60 years old) patients were recruited with age-matched controls (n?=?30, each group). DNA damage score, plasma malondialdehyde (MDA) and protein carbonyl content were measured for oxidative damage markers. Antioxidants such as erythrocyte glutathione (GSH), oxidised glutathione (GSSG), and glutathione peroxidase activity (GPx), superoxide dismutase (SOD) and catalase (CAT) were also determined. DNA damage score and protein carbonyl content were significantly higher in both PCAD and CAD when compared to age-matched controls while MDA level was increased only in PCAD (p<.05). In contrast, GSH, GSH/GSSG ratio, α-tocotrienol isomer, and GPx activity were significantly decreased, but only in PCAD when compared to age-matched controls. The decrease in GSH was associated with PCAD (OR?=?0.569 95%CI [0.375???0.864], p?=?.008) and cut-off values of 6.69?μM with areas under the ROC curves (AUROC) 95%CI: 0.88 [0.80–0.96] (sensitivity of 83.3%; specificity of 80%). However, there were no significant differences in SOD and CAT activities in all groups. A higher level of oxidative stress indicated by elevated MDA levels and low levels of GSH, α-tocotrienol and GPx activity in patients below 45 years old may play a role in the development of PCAD and has potential as biomarkers for PCAD.     

Angiotensin II,as well as 5-hydroxytriptamine,is a potent vasospasm inducer of saphenous vein graft for coronary artery bypass grafting in patients with diabetes mellitus

Diabetes mellitus (DM) is an important risk factor for adverse outcomes of coronary artery bypass grafting. The bypass grafts harvested from patients with DM tend to go into spasm after their implantation into the coronary circulation. To clarify the contribution of 5-hydroxytriptamine (5-HT) and angiotensin II (AngII) in the bypass graft spasm, we examined the contractile reactivity to 5-HT or AngII of isolated human endothelium-denuded saphenous vein (SV) harvested from DM and non-DM patients. The 5-HT-induced constriction of the SV was significantly augmented in the DM group than in the non-DM group, which is similar to our previous report. AngII-induced constriction of the SV was also significantly augmented in the DM group than the non-DM group. Especially in the non-DM group, the AngII-induced maximal vasoconstriction was markedly lower than the 5-HT-induced one. Meanwhile, the increasing rates of AngII-induced vasoconstriction in the DM group to the non-DM group were significantly greater than those of 5-HT-induced vasoconstriction. These results indicate that 5-HT is a potent inducer of SV graft spasm in both DM and non-DM patients, while AngII is a potent inducer of SV graft spasm only in patients with DM. Furthermore, the protein level of AngII AT₁ receptor (AT₁R), but not the protein level of 5-HT_2A receptor, in the membrane fraction of the SV smooth muscle cells of DM patients was significantly increased as compared with that of the non-DM patients. These results suggest that the mechanism for hyperreactivity to AngII in the SV from DM patients is due to, at least in part, the increase in the amount of AT₁R on membrane of the SV smooth muscle cells.     

Blood levels of corticosteroid-binding globulin, total cortisol and unbound cortisol in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass

Previous studies have demonstrated a persistent rise in serum cortisol concentrations after cardiac surgery. To further investigate this finding and to evaluate the effect of hemodilution that occurs with the onset of cardiopulmonary bypass (CPB), concentrations of cortisol-binding globulin (CBG), total and unbound cortisol, and packed cell volume (PCV) were studied in 28 patients undergoing coronary artery bypass graft surgery. All patients received a standardized general anesthetic using a balanced technique with sufentanil, isoflurane, and midazolam. Blood was collected preoperatively, intraoperatively during CPB, and postoperatively in the evenings on the day of surgery and on the first and second postoperative day. Cortisol and CBG concentrations were measured by radioimmunoassay and were used to calculate the fraction of unbound cortisol. Serum CBG and cortisol concentrations corrected for hemodilution were significantly higher than non-corrected values. Perioperatively, CBG measurements were significantly intercorrelated. Intraoperatively, total and unbound cortisol concentrations were not significantly increased compared to preoperative values. Postoperatively up to the end of the study period serum concentrations of total and unbound cortisol were significantly increased compared to baseline values. Our results suggest that hemodilution occurs in all patients during cardiac surgery and continues up to the second postoperative day. This may lead to an underestimation of serum cortisol and CBG concentrations in patients undergoing heart surgery with CPB. Intraoperatively, concentrations of total and unbound cortisol were not significantly elevated. The postoperative rise in serum total cortisol concentration was accompanied by an increase in unbound cortisol concentration. The postoperative increase of unbound cortisol concentrations in patients undergoing cardiac surgery with CPB was largely due to an increase in cortisol secretion.     

Natriuretic peptides and endothelin-1 in patients undergoing coronary artery bypass grafting

Off-pump coronary artery bypass grafting (CABG) is an alternative to conventional CABG using cardiopulmonary bypass. Off-pump technique reduces the complications of CABG performed with extracorporeal circulatory assistance (Lancey et al. 2000; Mack et al. 2004a,b). The object of this study was to compare peri- and postoperative time courses of vasoactive peptides - atrial natriuretic poptide (ANP), brain natriuretic poptide (BNP) and endothelin-1 (ET-1) in off-pump versus on-pump CABG. 22 patients, who underwent on-pump (group A, n = 11) or off-pump CABG (group B, n = 11) were studied. The peri- and postoperative time courses of plasma ANP and BNP were similar in both groups. A statistically significant difference between ET-1 plasma level 2 h after surgery in the group A and ET-1 plasma level 2 h after surgery in the group B (2.46 + or - 1.14 pg/ml/Ht versus 0.74 + or - 0.09 pg/ml/Ht, p < 0.0001) was found. Different CABG techniques were not associated with significant changes in peri- and postoperative plasma ANP and BNP. By contrast, plasma ET-1 significantly rose in the group A 2 h after surgery, indicating endothelial damage.     

Relation between zinc, copper, and magnesium concentrations following cardiopulmonary bypass and postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting

Atrial fibrillation is the most frequently encountered arrhythmia following cardiac surgery. Since the essential trace elements zinc, copper, and magnesium are suspected to have an effect on postoperative atrial fibrillation, the concentrations of these elements were determined by flame atomic absorption spectrophotometry in the plasma of 60 patients undergoing elective coronary artery bypass grafting. Blood samples were collected every 30 min during cardiopulmonary bypass and postoperatively. Plasma concentrations of copper, zinc, and magnesium were measured with flame atomic absorption spectrophotometry. All patients were monitored by continuous electrocardiography until they became outpatients or immediately after atrial fibrillation had taken place. Atrial fibrillation occurred in 13 of the 60 patients, corresponding to 21.7%. The zinc and copper concentrations at postoperative days 1 and 3 were significantly different (P < 0.05) between patients with and without atrial fibrillation. The concentrations of zinc following cardiopulmonary bypass recovered more slowly in patients with postoperative atrial fibrillation than in patients without it. Whether or not supplemental zinc could lower the incidence of postoperative atrial fibrillation should be evaluated in future prospective randomized clinical trials.     

Release of pro-inflammatory mediators during myocardial ischemia/reperfusion in coronary artery bypass graft surgery

Inflammation has been reported to play an important role in cardiac surgery under cardiopulmonary bypass due to systemic endotoxemia. In order to develop strategies against this injury in future we studied the combined effect of a number of inflammatory mediators in myocardial ischemia/reperfusion. Coronary sinus blood samples of ten patients undergoing coronary artery bypass graft surgery (CABG) were obtained at three time intervals (1) before onset of bypass (2) 30 min after cross clamp, and (3) 10 min after removal of cross clamp. The samples were subjected to evaluate levels of nitric oxide byproducts (nitrite and nitrate and citrulline), inflammatory cytokines (interleukin-2, interferon- and interleukin-6), adhesion molecules, (CD62L and CD54), ratio of cell surface markers (CD4/CD8 and TCR/) cell activation markers (CD69 and HLA DR) and second messengers (protein kinase C, inositol 1,4,5 triphosphate and intracellular calcium levels). Ischemia and further reperfusion resulted in significant rise in nitrite and nitrate levels (p < 0.001), interleukin-6 (p < 0.01), CD62L (p < 0.001), CD69 (p < 0.05), protein kinase C (p < 0.001) and intracellular calcium (p < 0.001). A fall in CD4/CD8 ratio was observed on reperfusion. These changes during CABG show that ischemia/reperfusion leads to a release of an array of pro-inflammatory mediators of tissue injury, which could lead to pathophysiological changes. Hence the study suggests the need of some protective therapies against these inflammatory markers.     

Carbonyl groups: Bridging the gap between sleep disordered breathing and coronary artery disease

Abstract

Sleep disordered breathing (SDB) is related to coronary artery disease (CAD), but the mechanisms are uncertain. SDB is characterized by periods of intermittent hypoxia and free radical formation. This study tested the hypothesis that carbonylation can be the link between SDB and CAD. It included 14 cases with CAD and 33 controls with <50% coronary narrowing. CAD cases have higher erythrocyte carbonyl levels than controls (p = 0.012). Positive correlation was observed between apnea-hypopnea index (AHI) and erythrocyte carbonyl concentration (ρ = 0.310; p = 0.027). To predict CAD, including as regressors: AHI, erythrocyte carbonyl, gender, age and body mass index, the significant variables in the Poisson multiple regression model were AHI and erythrocytes carbonyl. An increase of 1 pmol/gHb in erythrocyte carbonyl levels increases by 1.8% the risk of CAD and one unit of AHI increases by 3.8% the risk of CAD. The present findings represent the first evidence in humans that SDB may cause CAD through protein carbonylation.     

Effects of atorvastatin and aspirin combined therapy on inflammatory responses in patients undergoing coronary artery bypass grafting

This study was conducted to compare the effects of atorvastatin plus aspirin combined therapy on inflammatory responses, endothelial cell function, and blood coagulation system in patients undergoing coronary artery bypass grafting (CABG) to aspirin monotherapy. The patients were randomized into atorvastatin plus aspirin combined therapy group and aspirin monotherapy group. Reduced total cholesterol in the combined therapy group was found in a short term of medication for 14 days. On postoperative day (POD)-14, inhibitory effects of the combined therapy on whole blood aggregation as well as platelet activation assessed by flow cytometry were stronger than those of the monotherapy. Furthermore, cytokine, cytokine receptors, c-reactive protein and α1-acid glycoprotein in the combined therapy group were down-regulated on POD-14. At the same time, circulating levels of thromboxane A₂, vascular endothelial growth factor and thrombin–antithrombin III complex as well as P-selectin, L-selectin and intercellular adhesion molecule-1 were down-regulated, while E-selectin and transforming growth factor-β1 was up-regulated. Atorvastatin plus aspirin combined therapy may improve inflammatory responses, accelerated platelet function, vascular endothelial cell function, blood coagulation system at the early stage such as 14th day after CABG. In conclusion, atorvastatin and aspirin combined therapy may bring beneficial effects to the patient after CABG.