Aortocoronary Bypass Grafting Research Articles

Evaluation of Venous and Arterial Conduit Patency by 16-Slice Spiral Computed Tomography

Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16x0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.

Therapeutic Effects of l‐Carnitine and Propionyl‐l‐carnitine on Cardiovascular Diseases: A Review

Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl-CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high-energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti-ischemic properties. In small short-term studies, levocarnitine acts as an antianginal agent that reduces ST segment depression and left ventricular end-diastolic pressure. These short-term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing. These cardioprotective effects have been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients, there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation of long-chain acyl-CoA, which facilitates the production of free radicals by damaged mitochondria; (2) improving repair mechanisms for oxidative-induced damage to membrane phospholipids; (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium of long-chain acyl-CoA; and (4) reducing the ischemia-induced apoptosis and the consequent remodeling of the left ventricle. Propionyl-L-carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase, and it increases cellular carnitine content, thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl-L-carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate, propionate, which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase-2 studies in chronic heart failure patients showed that long-term oral treatment with propionyl-L-carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl-L-carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl-L-carnitine improves exercise capacity in patients with heart failure, but preserved cardiac function.

Association of high serum concentration of the third component of complement (C3) with pre-existing severe coronary artery disease and new vascular events in women

Atherosclerosis is an inflammatory disease. The complement system plays an important role in the atherosclerotic process. However, lesser data is available on the possible role of C3 as a risk factor for atherosclerosis. Therefore, in a follow up study we determined C3 levels in 266 patients with pre-existing severe coronary artery disease (CAD) and compared their serum C3 concentrations with the cause of the disease. We investigated whether C3 levels predict the major complications of severe CAD during a 5-year long follow up period in patients, who have received an aorto-coronary bypass graft surgery. C3 concentrations were elevated in the patients with severe CAD compared to 182 healthy controls, and women had higher C3 concentrations than men. Pathological C3 levels (C3≥1.8 g/L) were able to predict major complications of atherosclerosis (death by cardiac events, new acute myocardial infarction, stroke, carotid surgery and peripheral arterial disease) that developed during the follow up period only in women (OR: 4.1, 95% C.I. 1.23–13.61, p = 0.0249) independent of other risk factors for atherosclerosis. Our data supports the assumption that high C3 indicates the progression of atherosclerosis as a special marker of chronic inflammation.

Multislice CT of the heart: clinical applications

Since the introduction of last generation multislice MSCT systems and the development of simultaneous electrocardiographic-tracing image acquisition and retrospective reconstruction techniques into clinical routine, cardiac MSCT has been considered a very useful non-invasive technique for the study of cardiac pathology in the daily clinical practice. One of the main clinical applications of this diagnostic technique is the evaluation of the coronary arteries including detection and quantification of coronary calcium, multislice CT coronary angiography (anatomy, anatomical variants and anomalies of the origin and course), the angiographic evaluation of the patency of aortocoronary by-pass grafts and coronary stents, and plaque characterization. The new reconstruction and postprocessing programs allow to obtain, in addition, parameters of myocardial morphology and contraction and cardiac function. Other clinical applications include the characterization of cardiac masses and the evaluation of the pericardium.

Gene delivery to aortocoronary saphenous vein grafts in a large animal model of intimal hyperplasia

Objective More than 50% of aortocoronary saphenous vein grafts are occluded 10 years after surgery. Intimal hyperplasia is an initial, critical step in the progression toward occlusion. To date, no clinically relevant large animal models of aortocoronary saphenous vein graft intimal hyperplasia have been fully characterized. Gene therapy holds promise as a novel treatment for aortocoronary saphenous vein graft intimal hyperplasia. The 2 objectives of this study are to characterize a canine model of aortocoronary saphenous vein graft intimal hyperplasia and to demonstrate that ex vivo gene delivery is possible in these grafts using adenoviral vectors. Methods Ten dogs underwent aortocoronary bypass grafting using saphenous veins. Six dogs underwent serial arteriograms to monitor graft patency. On postoperative day 90, the dogs were killed and their grafted and nongrafted saphenous veins were studied histologically. Four dogs underwent the same procedure, but their saphenous veins were treated with 1 × 10 12 total viral particles of a replication-deficient, recombinant adenovirus containing β-galactosidase (n = 2) or the β-adrenergic receptor kinase carboxyl terminus (n = 2). These animals were killed on postoperative day 7 for determination of transgene expression. Results All grafts were demonstrated patent by arteriogram before the animals were killed. The mean intimal area of the saphenous vein grafts was increased when compared with that of the nongrafted saphenous veins (2.83 mm 2 vs 0.09 mm 2, P < .0008). Adenoviral-treated saphenous vein grafts demonstrated positive transgene expression either by X-gal staining (β-galactosidase) or Northern analysis (β-adrenergic receptor kinase carboxyl terminus). Conclusion This study characterizes a clinically relevant canine model of aortocoronary saphenous vein graft intimal hyperplasia. In addition, it demonstrates that adenoviral vectors can be delivered ex vivo to the saphenous vein graft vessel wall at subphysiologic distension pressures. This model may be used in future studies to manipulate molecular targets critical in aortocoronary saphenous vein graft intimal hyperplasia.

Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease

Apolipoprotein C-III (apoC-III) is a marker of triglyceride (TG)-rich lipoproteins, which are often increased in metabolic syndrome (MS). The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apoC-III levels. To evaluate the contribution of apoC-III levels and T-455C polymorphisms in the coronary artery disease (CAD) risk of MS patients, we studied 873 patients, 549 with CAD and 251 with normal coronary arteries. Patients were classified also as having or not having MS (MS, n = 270; MS-free, n = 603). Lipids, insulin, apolipoprotein levels, and APOC3 T-455C genotypes were evaluated. ApoC-III levels were significantly increased in MS patients, and the probability of having MS was correlated with increasing quartiles of apoC-III levels. MS patients with CAD had significantly higher apoC-III levels than did CAD-free MS patients. The carriership for the -455C variant multiplied the probability of CAD in MS in an allele-specific way and was associated with increased apoC-III and TG levels. Obesity was less frequent in MS carriers of the -455C allele than in MS noncarriers (21.6% vs. 34.8%, P < 0.05). In conclusion, apoC-III-rich lipoprotein metabolism and the APOC3 polymorphism have relevant impacts on the CAD risk of MS patents.

Randomized comparison of distal protection with a filter-based catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts

Randomized comparison of distal protection with a filter-based catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts

Circulation extracorporelle sous lépirudine (Refludan ®) dans un contexte de thrombopénie induite par l’héparine

Lepirudin is an alternative anticoagulant therapy in heparin-induced thrombocytopenia (HIT) during cardiopulmonary bypass (CPB). We report a case of a female patient with HIT referred for aortocoronary bypass graft despite persistence of antibodies to platelet factor 4–heparin complexes. Anticoagulation management is described. Whole blood hirudin concentration attempted during CPB was above 4 μg ml –1. To obtain this concentration, lepirudin administration was managed as follows: 0.1 mg kg –1 h –1 lepirudin during preoperative course, 0.2 mg kg –1 bolus just before CPB and 0.2 mg kg –1 in the priming solution, complementary boluses of 5 and 10 mg during procedure (according to whole blood ecarin clotting time). Aprotinin was administered simultaneously according to Royston protocol. Anticoagulation was monitored with whole blood ecarin time performed in the operation room (patient’s whole blood was diluted one half and one third with normal whole blood; in vitro calibration curve was constructed using normal whole blood spiked with lepirudin). CPB duration was 73 min. When measured, whole blood hirudin concentration was 3.8–5.8 μg ml –1. Total lepirudin administration was 44 mg. No haemorrhagic or thrombotic events were observed during surgical procedure and postoperative course. Despite lepirudin administration is not yet clearly precise for CPB procedure, its use seems adapted and safe in subjects without renal insufficiency but requiring precise coordination for anaesthesiological, surgical and biological teams.

RETRACTED: Influence of prolonged cardiopulmonary bypass times on splanchnic perfusion and markers of splanchnic organ function

Cardiopulmonary bypass (CPB) is known to have considerable negative impact on perfusion and organ function. The effects of the duration of CPB on markers of splanchnic organ function was studied. Consecutive patients undergoing elective aorto-coronary bypass grafting with CPB times (CPBT) of either less than 70 minutes (n = 15) or more than 80 minutes (n = 15) were prospectively studied. Splanchnic perfusion was assessed by measuring arterial and gastric mucosal PCO2 and calculating PCO2gap. Hepatic function was evaluated by monoethylglycinexylidide (MEGX) test and by measuring alpha-glutathione S-transferase (alpha-GST). Concentration of pancreatitis-associated protein was measured to assess pancreatic integrity. Measurements were performed after induction of anesthesia, at the end of surgery, 4 hours after arrival in the intensive care unit, and on postoperative day 1. The mean (+/- standard deviation) CPBT were 54 +/- 12 minutes and 99 +/- 16 minutes, respectively. PCO2gap increased significantly more in the group with CPBT of more than 80 minutes than in that with CPBT of less than 70 minutes, at +15 +/- 4 mm Hg versus +8 +/- 3 mm Hg, respectively, indicating reduction in splanchnic perfusion by longer CPBTs. Postoperative MEGX concentrations were significantly lower and postoperative alpha-GST concentrations were significantly higher in the group with CPBT of more than 80 minutes than in that with CPBT of less than 70 minutes. Plasma levels of pancreatitis-associated protein remained similar in both groups throughout the study period. In our patients with CPBT of more than 80 minutes, splanchnic perfusion and hepatocelluar integrity were moderately affected, whereas pancreatic function remained almost unchanged. Studies including a larger patient population are necessary to assess whether protective approaches would be helpful in patients undergoing complex cardiac surgery with very long CPBT.

Gene expression profiling of human stenotic aorto-coronary bypass grafts by cDNA array analysis.

Aorto-coronary bypass graft disease with its increasing clinical signification represents an unsolved problem in cardiological and heart surgery practice. Late occlusion of autologous saphenous vein grafts is due to medial and neointimal thickening secondary to migration and proliferation of smooth muscle cells (SMCs) and the subsequent formation of atherosclerotic plaques. This study is aimed at identifying differentially expressed genes in human stenotic bypass grafts to detect unknown pathomechanism and to identify novel targets for prophylactic treatment options. Stenotic saphenous aorto-coronary bypass grafts (n=5) were retrieved during re-do aorto-coronary bypass surgery. Ungrafted saphenous vein segments (n=5) were taken from the same group of patients and served as internal controls. cDNA samples were prepared and hybridized to cDNA arrays. Some of the differentially expressed genes complied with expected gene expression including upregulation of c-jun and CDK10. In addition, previously unidentified gene expression patterns were detected such as upregulation of HSP70, fibronectin1, erbB3 proto-oncogene and c-myc. To confirm the latter finding, upregulation of c-myc in neointimal and medial SMCs of stenotic graft segments was confirmed by in situ hybridization studies and by immunohistochemistry. Gene expression patterns of human stenotic bypass grafts retrieved by re-do operations can be reliably analyzed by cDNA array technology. With this technique, new therapeutic targets in patients could be identified as shown by the findings regarding c-myc. c-myc is a proto-oncogene acting as a transcription factor and blocking c-myc has shown a reduction of neointima formation in animal models. Our study yields a rational for the use of antisense c-myc oligonucleotides to reduce neointima formation and to avoid stenosis in patients.

Surgical Treatment of Ventricular Septal Defect Complicating Acute Myocardial Infarction. Experience of a North Italian Referral Hospital

The purpose of our study was to evaluate the clinical outcome of postinfarction ventricular septal defect (VSD) of patients referred to our institution for surgical treatment, by assessing the role of several operative, pre- and post-operative variables on mortality. The medical records of 58 consecutive patients (mean age 73±7 years), operated on after 14±12 days from the acute myocardial infarction were retrospectively reviewed and the data were analyzed. Associated procedures were left ventricular reconstruction in 13 patients and aortocoronary bypass grafting in 47 (81%). The overall operative, in-hospital mortality rate was 52% (75% in patients operated on within the first week and 16% if time from infarct to surgery was &gt;3 weeks). Time from AMI to surgery and time from hospital admission to operation were significantly shorter in nonsurvivors ( p=0.003 and 0.012, respectively). Other pre-operative variables significantly associated with mortality were: cardiogenic shock, pulmonary pressure, VSD diameter. In conclusion, time from AMI to operation appears to be a very important prognostic factor. However, size of VSD and hemodynamic conditions significantly influence the mortality. Moreover, concomitant procedures of revascularization can be safely performed, when required, as actually occurs in most cases.

Surgical treatment of ventricular septal defect complicating acute myocardial infarction. Experience of a north Italian referral hospital

The purpose of our study was to evaluate the clinical outcome of postinfarction ventricular septal defect (VSD) of patients referred to our institution for surgical treatment, by assessing the role of several operative, pre- and post-operative variables on mortality. The medical records of 58 consecutive patients (mean age 73±7 years), operated on after 14±12 days from the acute myocardial infarction were retrospectively reviewed and the data were analyzed. Associated procedures were left ventricular reconstruction in 13 patients and aortocoronary bypass grafting in 47 (81%). The overall operative, in-hospital mortality rate was 52% (75% in patients operated on within the first week and 16% if time from infarct to surgery was >3 weeks). Time from AMI to surgery and time from hospital admission to operation were significantly shorter in non-survivors ( p=0.003 and 0.012, respectively). Other pre-operative variables significantly associated with mortality were: cardiogenic shock, pulmonary pressure, VSD diameter. In conclusion, time from AMI to operation appears to be a very important prognostic factor. However, size of VSD and hemodynamic conditions significantly influence the mortality. Moreover, concomitant procedures of revascularization can be safely performed, when required, as actually occurs in most cases.

Natural history of inadvertent aorta-saphenous vein-coronary vein bypass graft

Inadvertent distal anastomosis of an aortocoronary bypass graft to a coronary vein is a rare but potentially serious complication of coronary artery bypass surgery. We describe a patient in whom such a conduit was discovered only incidentally 17 years after its creation. This case illustrates the pertinent features of this anomaly and demonstrates that it can have a benign natural history.

Bispectral Index-Guided Anesthesia in Patients Undergoing Aortocoronary Bypass Grafting: Retracted

Lehmann, Andreas MD*; Karzau, Julia*; Boldt, Joachim MD*; Thaler, Elfi MD*; Lang, Johannes*; Isgro, Frank MD† Author Information

Fourier Transform Infrared Spectroscopy Application to Vascular Biology: Comparative Analysis of Human Internal Mammary Artery and Saphenous Vein Wall

Saphenous vein (SV) and internal mammary artery (IMA) are used for aorto-coronary bypass grafting. IMA is considered to be the graft of choice for coronary revascularization having a long-term patency compared to SV. The aim of this study is to investigate the structure of vascular wall using a new technical approach. We analysed the chemical composition of vessel wall layers (total lipid, lipid ester and protein) of 25 vascular segments (19 SV and 6 IMA) using Fourier transform infrared spectroscopy (FTIR). FTIR analysis showed that in intima layer lipid ester and protein concentration (expressed as arbitrary units) was significantly higher in SV (lipid ester = 0.020 ± 0.002; protein = 0.449 ± 0.022) than in IMA (lipid ester = 0.014 ± 0.002; protein = 0.342 ± 0.032). Moreover, the percentage of lipid ester on total lipid was significantly higher in SV (intima = 54.7 ± 2.9%; media = 78.4 ± 4.9%; adventitia = 83.9 ± 8.3%) wall layers compared to IMA ones (intima = 37.3 ± 4.9%; media = 45.4 ± 3.8; adventitia = 57.1 ± 4.8). These data suggest that a different chemical composition of wall layers could also be responsible for the morphological modifications observed in SV after grafting.

The Serum Cortisol:Cortisone Ratio in the Postoperative Acute-Phase Response

Objective: In a previous cross-sectional pilot investigation, an increase in the ratio of active cortisol to inactive cortisone in serum has been found as a general phenomenon during the acute-phase response. The aim of the present study was to further characterize this alteration of cortisol metabolism in patients undergoing elective cardiac bypass surgery. Methods: Cortisol and cortisone were quantified by use of liquid-chromatography tandem mass spectrometry in sera that were sampled preoperatively and on the first 4 postoperative days (POD) from 16 patients undergoing aortocoronary bypass grafting (7.00 a.m.). Results: The median serum cortisol concentration peaked on the first POD and then decreased statistically significantly until the end of the observation period: preoperatively, 245 nmol/l (IQR 198–331); 1st POD, 532 nmol/l (IQR 409–678 ); 4th POD, 373 nmol/l (IQR 306–493); p for trend = 0.019. In contrast, the cortisol:cortisone ratio was constantly increased approximately twofold on all POD compared to preoperative sampling: preoperatively, 5.4 (IQR 5.0–7.2); 1st POD, 11.3 (IQR 9.2–13.6); 4th POD, 9.9 (IQR 7.7–11.0), with no significant trend of normalization. Conclusion: Following major surgery, the substantial increase in the serum cortisol:cortisone ratio – reflecting a shift in the overall set-point of 11β-hydroxysteroid dehydrogenase activity – is more sustained than the increase in serum cortisol; the increase in the cortisol:cortisone ratio seems to be a long-term phenomenon of the activation of the hypothalamic-pituitary-adrenocortical system by surgical stress and systemic inflammation.

An experimental intraoperative quantitative echocardiographic study of myocardial perfusion in dogs

Myocardial contrast echocardiography is a valuable technique for demonstration and delineation of regions of myocardial underperfusion secondary to coronary occlusion and/or significant coronary stenosis. Various contrast materials have been used. The aim of this study was to determine whether myocardial contrast echocardiography by the original contrast agent AQ-DDT (albumin based), produced in the Institute for Cardiovascular Diseases, Clinical Center of Serbia in Belgrade can be used in the detection and quantification of regions of myocardial perfusion defects. In 14 adult open chest dogs the perfusion defect was produced by selective coronary ligations (30 seconds) and was observed with epicardial contrast two-dimensional echocardiography. For administration of contrast a modified pigtail catheter was positioned in the aorta just above the aortic valves. In this way the perfusion regions of the left main and right coronary artery were included. The left anterior descending and left circumflex artery could not be selectively injected with contrast agent and their individual perfusion areas were not clearly demonstrated. In all cases contrast echocardiography images of the left ventricle were obtained in a short-axis cross-sectional view at the mid-papillary muscle level. Forty-two injections of AQ-DDT for perfusion analysis were done, and were recorded on a VHS recorder. Quantification of the quality in demonstrating myocardial perfusion was scored as good, poor or without visual echocardiographic effect, by an investigator experienced in echocardiography, immediately and one month later. There was 100% agreement in the scoring. Our results indicated that agent AQ-DDT produces a good contrast effect (echocardiography visualization) in dogs and has the potential to demonstrate regional perfusion defects of the myocardium. Its potential role in human medicine, for diagnosis and evaluation of the results of interventional therapy, especially during aortocoronary bypass graft surgery, should be evaluated.

Mid-term results of an endovascular stent-graft by means of median sternotomy for distal aortic arch aneurysm.

Migration and perigraft leakage are major problems after endovascular stent graft (EVG) by means of median sternotomy for distal aortic arch aneurysm. Anchoring sutures have been applied to prevent these problems. We evaluate the mid-term results and the efficacy of anchoring sutures. The operation was performed on 19 men and 2 women with a mean age of 70 years (range, 59-81). The aneurysms were 19 true (12 fusiform, 7 saccular), 1 chronic dissection, and 1 penetrating aortic ulcer. EGVs were implanted by way of the aortic arch under retrograde cerebral perfusion in 13 patients and selective cerebral perfusion in 8. Total arch replacement was performed in 2 patients, and aortocoronary bypass grafting in 4. Anchoring sutures to fix the EVG were applied in 9 patients. The average follow-up period was 28 months (range, 2-56). There were no operative mortalities, but 1 paraplegia, 1 stroke, and 2 cases of temporary spinal cord dysfunction occurred. All aneurysms were thrombosed completely after surgery and reduced in diameter (66.9 +/- 17.4 mm to 57.3 +/- 15.7 mm, p < 0.0001). EVG-related complications arose in 4 patients. A chronic Type B dissection revealed impending rupture because of false lumen infection 1 year after operation, and redo surgery was performed. Migration occurred in 3 patients, all with fusiform aneurysms. One of these had a graft kink 1 year later. Another showed aneurysm enlargement with serous pleural effusion 3 years after operation. The third required redo surgery because of perigraft leakage at 3 years after surgery. There were 2 late deaths caused by stroke. There were no EVG-related complications in the 9 cases in which anchoring sutures were applied and in the 7 cases with saccular aneurysms. No spinal cord dysfunction occurred in 8 cases with low-flow antegrade perfusion by way of both axillary arteries while the aorta was opened. Logistic regression analysis showed significant relevance to complications of large aneurysms, greater than 80 mm in diameter. A large aneurysm tends to give rise to complications involving EVG migration. Anchoring sutures of EVG may prevent EVG-related complications.

Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts: a pooled analysis of five randomized clinical trials.

Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions were assessed at 30 days and 6 months. Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P=0.006) and 6 months (4.7% versus 2.0%, P<0.001). Revascularization of a graft was identified as an independent predictor of death, myocardial infarction, or revascularization at 6 months (hazard ratio, 1.42; 95% CI, 1.24 to 1.63; P<0.001). Among patients undergoing graft PCI, the incidence of the triple end point at 30 days was 16.5% in the platelet GP IIb/IIIa inhibitor group and 12.6% in the placebo group (odds ratio, 1.38; 95% CI, 0.85 to 2.24; P=0.18). At 6 months, 39.4% of patients randomized to GP IIb/IIIa inhibitors and 32.7% of patients allocated to placebo had an ischemic event (hazard ratio, 1.29; 95% CI, 0.97 to 1.72; P=0.07). Intravenous platelet GP IIb/IIIa receptor inhibition does not improve outcomes after PCI of bypass grafts. In the absence of mechanical emboli protection, this procedure is associated with high incidence of death and nonfatal ischemic events.

Intraoperative transfection of vein grafts with the NFκB decoy in a canine aortocoronary bypass model: a strategy to attenuate intimal hyperplasia

Background The nuclear transcriptional factor NFκB is reported to play an important role in the expression of genes for neutrophil and macrophage chemotactic factors, adhesion molecules, and cell cycle–regulating proteins. In aortocoronary bypass surgery, the saphenous vein often develops vein graft disease. Here, we investigated whether transfection of a cis element decoy oligodeoxynucleotide of NFκB (NFκB decoy) into the vein graft wall suppresses neointimal hyperplasia and the differentiation of medial smooth muscle cells. Methods We established a canine aortocoronary bypass grafting model that has a saphenous vein graft between the left anterior descending coronary artery and the descending aorta. Pressure-mediated transfection of a scrambled (SD group; n = 5) or NFκB decoy (ND group; n = 5) into the graft wall was performed intraoperatively. The grafts were gently harvested at 4 weeks postoperative, and the middle portion of the graft was examined histopathologically. Results The average neointimal area of the ND group was significantly suppressed (SD group, 2.63 ± 1.00 mm 2 vs ND group, 0.88 ± 0.66, p < 0.05), and the differentiation and proliferation of the medial smooth muscle cells in the ND group were also suppressed (proliferating cell nuclear antigen index: SD group, 56 ± 24 vs ND, 13 ± 4, p < 0.05). Conclusions These results demonstrated the efficacy of intraoperative transfection of the NFκB decoy into the vein graft wall for attenuation of neointima formation.