Vein Coronary Artery Bypass Grafts Research Articles

Nitric oxide donating aspirins: novel drugs for the treatment of saphenous vein graft failure

Background A new class of nitric oxide donating aspirin (NO-ASA) drugs may increase the therapeutic impact of aspirin in saphenous vein coronary artery bypass grafting (CABG) not only through the inhibition of thrombosis but also through a reduction of vasospasm and inhibition of vascular smooth muscle cell (VSMC) proliferation (effects that are inhibited by NO but not ASA). In order to test this proposal the effect of three NO-ASA drugs (NCX 4040, NCX4050, and NCX4060) on in vitro relaxation and cyclic guanosine monophosphate (cGMP) formation in the human isolated saphenous vein and the proliferation of human VSMCs was investigated. Methods Saphenous vein segments were obtained from 30 patients undergoing CABG (median age, 59 years; range, 49 to 68). The effect of the NO-ASA adducts, ASA alone, and sodium nitroprusside (NO donor) were investigated on (1) relaxation of phenylephrine-stimulated contraction using an organ bath, (2) cyclic guanosine monophosphate (cGMP) formation using an enzyme-linked immunosorbent assay, and (3) the proliferation of VSMCs derived from saphenous vein using bromo-deoxyuridine (BRDU) incorporation. Results All three NO-ASA adducts (at concentrations that inhibited responses by 50% [IC 50s] between 1 μmol/L and 100 μmol/L) and nitroprusside (at IC 50s between 0.5 and 10 μmol/L) elicited relaxation of isolated human saphenous vein, promoted cGMP formation, and inhibited VSMC proliferation whereas ASA alone (up to 100 μmol/L) had no effect on any variable. Conclusions These data indicate that the NO-ASA adducts by virtue of their capacity to release NO and stimulate guanylyl cyclase may be useful not only in the prevention of thrombosis following CABG but also the reduction of saphenous vein graft spasm and neointima formation.

Both ICAM-1- and VCAM-1-Integrin Interactions Are Important in Mediating Monocyte Adhesion to Human Saphenous Vein

Atherosclerosis underlies late occlusion of human saphenous vein (HSV) coronary artery bypass grafts. Monocyte infiltration is implicated, but its mechanisms are unclear given that HSV normally expresses the ICAM-1 but not the VCAM-1 adhesion molecule. To define the mechanisms underlying monocyte adhesion, samples of HSV taken from coronary artery bypass graft patients were co-cultured with human monocytes and adherent monocytes were quantified by immunocytochemistry for CD68 on transverse sections. Pre-treatment of veins with anti-ICAM-1 antibodies reduced monocyte adhesion (monocytes/mm of section) from 7.2 ± 1.5 to 3.1 ± 0.7 (p < 0.05, n = 6), but the effect of anti-VCAM-1 was not significant (4.1 ± 0.7). Paradoxically, pre-treatment of monocytes with either anti-β₂-integrins, the counter-receptor of ICAM-1, or anti-α₄ integrins, the counter-receptor of VCAM-1, significantly reduced adhesion (1.8 ± 0.6 and 2.4 ± 0.7, respectively, p < 0.05). These results were clarified by immunocytochemistry, which confirmed that VCAM-1 expression was absent in harvested vein but was induced in the endothelium during co-culture. Consistent with this, when anti-ICAM-1 or anti-VCAM-1 was present throughout co-culture, either of them reduced adhesion (from 4.2 ± 0.9 to 2.3 ± 0.5 and 2.2 ± 0.4, respectively, p < 0.02, n = 8) and there was no further effect of adding both (2.0 ± 0.5). These results demonstrate that both ICAM-1/β₂ and VCAM-1/α₄ integrin interactions mediate monocyte adhesion to HSV, possibly as part of a common pathway. These experiments imply that either integrin might be targeted to reduce monocyte infiltration into HSV grafts.

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis.

Patency of autologous human saphenous vein coronary artery bypass grafts (CABG) is compromised by intimal thickening and superimposed atherosclerosis, caused by migration of vascular smooth muscle cells (SMC) to the intima where they proliferate. Here, using adenoviral transfer, we have targeted SMCs using wild-type p53 (wt p53) overexpression. Initial in vitro analyses demonstrated that wt p53 overexpression had no effect on SMC proliferation but promoted apoptosis, which was inhibited by co-expression of bcl2 or crmA. Wt p53 inhibited SMC invasion through reconstituted matrices, a phenotype not affected by bcl2 or crmA. Overexpression of wt p53 in human saphenous vein before organ culture significantly induced apoptosis (P < 0.01, Student's t test) without affecting proliferation rates either in the media or in the intima. SMC migration was, however, significantly reduced by wt p53 (P < 0.01, Student's t test). Intimal thickening and the number of neointimal cells were reduced by 89% and 73%, respectively, after 14 days (P < 0.01 and P < 0.001, respectively, Student's t test). This study demonstrates that overexpression of wt p53 promotes apoptosis and inhibits migration of SMC leading to reduced intimal thickening. This maybe a useful approach for increasing patency rates in CABG procedures in the clinic.

Expression of intercellular adhesion molecules in human saphenous veins: effects of inflammatory cytokines and neointima formation in culture

Atherosclerosis causes occlusions in as many as 50% of human saphenous vein coronary artery bypass grafts. Monocyte infiltration is an early step in saphenous vein-graft atherosclerosis, however, comparatively little is known of its underlying mechanisms. As a first approach, we sought to define the occurrence, location and regulation of leukocyte adhesion molecules in human saphenous vein before and after surgical preparation for grafting, during neointima formation in culture and on stimulation with inflammatory cytokines. We compared the distribution of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and platelet endothelial cell adhesion molecule (PECAM-1 or CD-31) in endothelial cells and smooth muscle cells (SMCs), using immunocytochemistry. ICAM-1 was expressed on endothelial cells before culture and on both endothelial cells and medial or neointimal SMCs after culturing vein for 14 days in 30% foetal bovine serum or after culturing for 24 h with TNF-α. Relative tissue levels of ICAM-1 measured by Western blotting were significantly elevated by culturing freshly-isolated (0.02±0.01 to 0.18±0.03) and surgically-prepared (0.02±0.01 to 0.14±0.03; n=6) veins or following TNF-α treatment of surgically-prepared veins (0.04±0.01 to 0.32±0.11, n=7). VCAM-1 was undetectable before or after culturing but was strongly upregulated on endothelial cells by incubation with the cytokines TNF-α, IL-1α or interferon-γ. PECAM-1 was expressed constitutively on endothelial cells. We conclude that human saphenous vein expresses several adhesion molecules capable of mediating monocyte migration. The increased expression of ICAM-1 in SMC after culturing or cytokine treatment and of VCAM-1 in endothelial cells suggests that interactions with β1 and β2 integrins are important pathways for stimulated monocyte ingress into human saphenous vein grafts.

Inhibition of late vein graft neointima formation in human and porcine models by adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-3.

Autologous saphenous vein coronary artery bypass graft surgery is complicated by late graft failure due to neointima formation and subsequent atherosclerosis. Growth factors and metalloproteinases (MMPs) act in concert to promote neointima formation. Tissue inhibitor of metalloproteinase-3 (TIMP-3), an extracellular matrix-associated MMP inhibitor, uniquely promotes apoptosis of isolated vascular smooth muscle cells. Here, we overexpressed TIMP-3 at the luminal surface of human saphenous veins before organ culture and in pig saphenous veins before interposition grafting into carotid arteries in vivo to assess neointima formation. In both models, high TIMP-3 immunoreactivity occurred in the luminal and upper medial extracellular matrix after adenovirus delivery. MMP activity measured by in situ zymography was reduced throughout the veins, confirming a bystander effect. By use of 3 independent techniques, apoptosis levels in the neointima and medial layer were significantly elevated by TIMP-3 overexpression. Neointima formation was reduced by 84% in 14-day human organ cultures and by 58% in 28-day pig vein grafts (both P<0.05). In contrast, TIMP-2 overexpression had no effect on neointima formation in vivo. Our results highlight the potential therapeutic benefit for TIMP-3 overexpression to reduce neointima formation associated with late vein graft failure.

Involvement of Dendritic Cells in Long-Term Aortocoronary Saphenous Vein Bypass Graft Failure

Antigen-presenting dendritic cells are present in atherosclerotic lesions in human arterial intima, but have not been investigated in atherosclerotic and hyperplastic stenotic lesions that affect vein grafts used as arterial conduits. This study was undertaken to examine whether dendritic cells are present in aortocoronary artery saphenous vein bypass grafts affected by high-grade atheromatous stenosis. Stenotic saphenous vein coronary artery bypass grafts (angiographic luminal stenosis &gt; 75%) were harvested from 10 patients (nine male, one female), aged 42–71 years (mean 56.5) at re-do operation. The mean time interval from bypass surgery to the excision of stenotic grafts was 11.5 years (range 2–21). The specimens were fixed in 10% buffered formalin, embedded in paraffin blocks and the sections stained with antibodies to S-100 (to identify dendritic cells). CD3 (T cells). CD68 (macrophages), von Willebrand factor (endothelial cells) and α-smooth muscle actin (smooth muscle cells) using avidin-biotin complex immunoperoxidase technique. Normal veins were obtained during saphenous vein femora-popliteal grafting. The stenotic venous grafts showed histological features typical of extensive arterialization, intimal hyperplasia, atherosclerotic plaque-like lesions, calcification and thrombosis. In areas of intimal hyperplasia, S-100-positive cells were distributed irregularly among smooth muscle cells. S-100-positive dendritic cells were seen most frequently within atherosclerotic plaque-like lesions where they co-localized with CD3+ cells and CD68+ cells. S-100-positive dendritic cells were also seen accumulating within calcific foci. No S-100-positive ceils were found in normal, ungrafted saphenous veins. We conclude that dendritic cells are present in aortocoronary saphenous vein bypass grafts affected by high grade stenosis. Dendritic cells are probably involved in immune mechanisms of atherogenesis through their interactions with T cells and macrophages. The accumulation of dendritic cells within calcific foci suggests their contribution to the calcification of stenotic venous grafts.

Involvement of dendritic cells in long-term aortocoronary saphenous vein bypass graft failure

Antigen-presenting dendritic cells are present in atherosclerotic lesions in human arterial intima, but have not been investigated in atherosclerotic and hyperplastic stenotic lesions that affect vein grafts used as arterial conduits. This study was undertaken to examine whether dendritic cells are present in aortocoronary artery saphenous vein bypass grafts affected by high-grade atheromatous stenosis. Stenotic saphenous vein coronary artery bypass grafts (angiographic luminal stenosis >75%) were harvested from 10 patients (nine male, one female), aged 42–71 years (mean 56.5) at re-do operation. The mean time interval from bypass surgery to the excision of stenotic grafts was 11.5 years (range 2–21). The specimens were fixed in 10% buffered formalin, embedded in paraffin blocks and the sections stained with antibodies to S-100 (to identify dendritic cells), CD3 (T cells), CD68 (macrophages), von Willebrand factor (endothelial cells) and α-smooth muscle actin (smooth muscle cells) using avidin–biotin complex immunoperoxidase technique. Normal veins were obtained during saphenous vein femoro-popliteal grafting. The stenotic venous grafts showed histological features typical of extensive arterialization, intimal hyperplasia, atherosclerotic plaque-like lesions, calcification and thrombosis. In areas of intimal hyperplasia, S-100-positive cells were distributed irregularly among smooth muscle cells. S-100-positive dendritic cells were seen most frequently within atherosclerotic plaque-like lesions where they co-localized with CD3 + cells and CD68 + cells. S-100-positive dendritic cells were also seen accumulating within calcific foci. No S-100-positive cells were found in normal, ungrafted saphenous veins. We conclude that dendritic cells are present in aortocoronary saphenous vein bypass grafts affected by high grade stenosis. Dendritic cells are probably involved in immune mechanisms of atherogenesis through their interactions with T cells and macrophages. The accumulation of dendritic cells within calcific foci suggests their contribution to the calcification of stenotic venous grafts.

Detection of Chlamydia pneumoniae but not cytomegalovirus in occluded saphenous vein coronary artery bypass grafts.

A causal relation between atherosclerosis and chronic infection with Chlamydia pneumoniae and/or cytomegalovirus (CMV) has been suggested. Whether the unresolved problem of venous coronary artery bypass graft occlusion is related to infection with C pneumoniae and/or CMV has not been addressed. Thirty-eight occluded coronary artery vein grafts and 20 native saphenous veins were examined. Detection of C pneumoniae DNA was performed by use of nested polymerase chain reaction (PCR). Homogenisates from the specimen were cultured for identification of viable C pneumoniae. Both conventional PCR and quantitative PCR for detection of CMV DNA were applied. Differential pathological changes (degree of inflammation, smooth muscle cell proliferation [MIB-1]) were determined and correlated to the detection of both microorganisms. C pneumoniae DNA could be detected in 25% of occluded vein grafts. Viable C pneumoniae was recovered from 16% of occluded vein grafts. Except for 1 native saphenous vein, all control vessels were negative for both C pneumoniae detection and culture. All pathological and control specimens were negative for CMV DNA detection. Pathological changes did not correlate with C pneumoniae detection. Occluded aorto-coronary venous grafts harbor C pneumoniae but not CMV. The detection of C pneumoniae in occluded vein grafts warrants further investigation.

Distribution of endothelin-1 (ET) receptors (ET A and ET B) and immunoreactive ET-1 in porcine saphenous vein–carotid artery interposition grafts

Proliferation of vascular smooth muscle cells (VSMC) is a principal event in neointima formation in saphenous vein–coronary artery bypass grafts. Since endothelin-1 (ET-1) promotes VSMC replication and ET-1 receptor antagonists inhibit neointima formation in arterial injury models, it is reasonable to propose that ET-1 may be involved in neointima formation in vein grafts. However, it is not known what alterations of ET-1 and its receptors (if any) occur in vein grafts. The objective of this study, therefore, was to investigate the distribution of ET-1 and ET-1 receptor subtypes (ET A and ET B) in porcine vein grafts. Unilateral interposition saphenous vein grafting was performed by end to end anastomosis after excision of a segment of carotid artery in Landrace pigs. One month after surgery, vein grafts, ungrafted saphenous veins and carotid arteries were excised, ET-1 immunoreactivity identified by immunocytochemistry and ET A and ET B receptor subtypes studied using autoradiography. In vein grafts, there was a greater density of ET A compared to ET B receptors in both the tunica media and neointima. ET A binding in the tunica media of ungrafted saphenous vein was greater than that in the carotid artery or vein grafts, but greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was located in endothelial cells and throughout the neointima of the vein graft. Dense ET-1 binding (to both ETA and ET B receptors) was also associated with microvessels in the adventitia within the graft. In vein grafts, there was strong ET B binding to neutrophils which were present in high numbers at the subendothelium and within the adventitia. It is concluded ET A receptors may play a role in vein graft thickening at the medial and neointimal VSMC level, whereas ET B receptors may play a role in microangiogenesis. The higher levels of ET A receptors in the tunica media of ungrafted saphenous vein relative to the carotid artery and vein graft may also render this conduit susceptible to neointima formation. These data indicate that studies on the effect of ET receptor antagonists on the pathobiology of vein graft disease is warranted.

Method for Creation of the Aortotomy Site for Saphenous Vein Grafts

Saphenous vein coronary artery bypass grafting requires a proximal anastomosis of the vein to the aorta. A variety of techniques have been described to create the aortotomy. We have developed a four-sided knife (Xcision Scalpel; patent pending, Research Medical, Inc, Midvale, UT) that facilitates the creation of a more uniform circular aortotomy. The purpose of this communication is to describe the knife and the technique for its use.

Influence of Procedural Success on Immediate and Long-Term Clinical Outcome of Patients Undergoing Percutaneous Revascularization of Occluded Coronary Artery Bypass Vein Grafts

ObjectivesThis study sought to determine whether successful recanalization of an occluded vein graft is associated with improvement in long-term clinical outcome. BackgroundCoronary angioplasty of occluded vein grafts is associated with a lower initial success rate and a higher complication rate than angioplasty of vein grafts with subtotal stenoses and native coronary arteries. Whether successful angioplasty improves clinical outcome is unknown. MethodsWe analyzed 77 consecutive patients who underwent angioplasty of an occluded saphenous vein coronary artery bypass graft between August 1983 and June 1994. Patients with a myocardial infarction in the previous 24 h were excluded from the study. ResultsThe mean age of the study cohort was 65 years; the mean (±SD) age of the treated grafts was 7.5 ± 3.9 years. As an adjunct to balloon angioplasty, stents were used in 9% of procedures, laser in 30%, and atherectomy in 16%, and thrombolytic therapy was administered in 23% of patients. The angioplasty success rate was 71%. Major complications within 30 days of the procedure included death in 5.2% of patients, Q wave myocardial infarction in 1.3% and repeat bypass surgery in 7.8%; these events occurred with similar frequency in patients in whom angiographic success was and was not achieved. Kaplan-Meier analysis comparing patients in whom angioplasty was successful (n = 55) and not successful (n = 22) revealed no differences in survival or occurrence of myocardial infarction or recurrent severe angina between the two groups in the 3 years after the procedure. Univariate analysis identified the age of the graft and use of newer interventional devices as predictors of death or myocardial infarction during this time period; procedural success was not associated with freedom from these adverse events after adjusting for these variables. ConclusionsAngioplasty of occluded vein grafts is associated with a low initial success rate and a high complication rate. Successful angioplasty does not appear to reduce the occurrence of adverse events in the 3 years after the procedure.

Growth factor production by arterial and vein grafts: Relevance to coronary artery bypass grafting

Occlusion caused by myointimal hyperplasia, atherosclerosis, or both is the main reason for late failure of saphenous vein coronary artery bypass grafts. On the other hand, internal mammary artery grafts are usually spared from atherosclerosis. Evidence exists that platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are involved in the genesis of myointimal hyperplasia and atherosclerosis. The aim of this study was to assess the production of PDGF and bFGF by arterial and vein grafts. In 20 inbred Lewis rats alpha 1 cm long segment of arterial graft was interposed at the level of the abdominal aorta. In a control group of 20 Lewis rats alpha 1 cm long segment of vein graft was implanted at the level of the abdominal aorta. Animals were killed 4 weeks after operation, and the grafts were studied in serum-free organ culture to assess the production of PDGF and bFGF. RESULTS. Arterial grafts produced a smaller quantity of PDGF and bFGF than vein grafts (p < 0.01) Higher mitogenic activity was present in the conditioned media from vein grafts than in the conditioned media from arterial grafts (p < 0.001). A large amount of myointimal hyperplasia was present in all vein grafts. This phenomenon could explain the rarity of atherosclerotic changes in internal mammary coronary bypass grafts.

Constitutive Nitric Oxide Synthase Is Expressed and Nitric Oxide-Mediated Relaxation Is Preserved in Retrieved Human Aortocoronary Vein Grafts

Although little is known about the endothelial cell function of human saphenous vein coronary artery bypass grafts, there is evidence to suggest that receptor-activated, endothelial-dependent relaxation mediated by nitric oxide is impaired. This study examines the expression and function of endothelial cell constitutive nitric oxide synthase (cNOS) of aortocoronary vein bypass grafts and human saphenous veins obtained from 10 patients undergoing repeat coronary artery bypass grafting for recurrent ischemic symptoms. Following precontraction with norepinephrine (10 -5 M), responses to acetylcholine (receptor-mediated, endothelium-dependent), calcium ionophore (A23187; receptor-independent, endothelium-dependent), and sodium nitroprusside (endothelium-independent) were assessed. Following total RNA extraction using phenol/guanidinium isothiocyanate from specimens of human saphenous vein and vein graft, a quantitative RNase Protection Assay (RPA) was performed using a cRNA riboprobe corresponding to a fragment of the human endothelial cell cNOS gene. Histologically, the vein grafts showed both intimal hyperplasia development and focal atherosclerosis formation compared to the saphenous veins. Scanning electron microscopy of the saphenous veins and the vein grafts showed an intact endothelium. Precontracted vein grafts did not relax in response to acetylcholine; in contrast, the saphenous vein relaxed in a dose-dependent manner to reach a maximal relaxation of 19 ± 4% precontracted tension. Saphenous veins and vein grafts relaxed in response to A23187 with maximal relaxation of 92 ± 5 and 73 ± 13%, respectively. Both vessels relaxed in a dose dependent manner to sodium nitroprusside. RPA normalized to β-actin showed similar levels of expression of endothelial cell cNOS equivalent to 1 pg of sense RNA in both the saphenous vein and vein graft. These data demonstrate that the endothelium of coronary artery vein grafts shows both expression and function of endothelial cell cNOS. However, the impaired NO-mediated relaxation of aortocoronary vein grafts in response to acetylcholine appears to be due to altered receptor activation of the endothelial cNOS system.

Cardiac Pacing Induced Flow Responses in Internal Thoracic Artery and Saphenous Vein Coronary Artery Bypass Grafts

The flow reactivity of an internal thoracic artery (ITA) graft and a vein graft for multiple coronary beds in response to different modes of cardiac pacing remains unclear. These experiments were conducted in 14 anesthetized dogs with the ITA or the vein grafted to the circumflex coronary artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle totally dependent upon the ITA graft or the vein graft. When the left main coronary artery was occluded and the heart rate was 120 beats per min, graft flow was 93.4 +/- 9.6 ml per min in the ITA, and 96.1 +/- 10.4 ml per min in the vein graft. Atrial pacing to increase heart rates 25% to 150 beats per min increased both the ITA graft flow (110.3 +/- 9.7 ml per min, p < 0.05 versus flow in sinus rhythm) and the vein graft flow (109.8 +/- 7.9 ml per min, p < 0.05 versus flow in sinus rhythm). The increases in flow in both cases were not attributable to changes in perfusion pressure. In contrast, ventricular pacing to the same heart rate decreased systemic pressure slightly, but insignificantly. Despite the slight decrease in perfusion pressure, ventricular pacing increased ITA flow (107.9 +/- 8.4 ml per min, p < 0.05 versus flow in sinus rhythm), but the increase in vein graft flow was not significant compared with flow in sinus rhythm (102.1 +/- 7.3 ml per min, p = ns versus flow in sinus rhythm).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing Induced Flow Responses in Internal Thoracic Artery and Saphenous Vein Coronary Artery Bypass Grafts

Cardiac Pacing Induced Flow Responses in Internal Thoracic Artery and Saphenous Vein Coronary Artery Bypass Grafts

1029-16 The Function of G-Proteins and Alpha-Adrenergic Receptors in Retrieved Human Vein Grafts

Although little is known about the pharmacology of the smooth muscle cells of human saphenous vein coronary artery bypass grafts, there is evidence to suggest that the function of G-proteins and alpha-adrenergic receptors is altered. This study examines the alpha-adrenergic function of smooth muscle cells of aorto-coronary vein bypass grafts and saphenous veins obtained from eight patients undergoing repeat coronary artery bypass grafting for recurrent ischemic symptoms. After removal from the patient, each specimen was placed into oxygenated Krebs solution, rapidly cleaned, dissected and patent segments sectioned into 5 mm rings (4 per vessel) for isometric tension studies to phenylephrine (10 -10 to 10 -4 M) alone and in the presence of the alpha-adrenergic 1A antagonist WB4101, the 1B antagonist chloroethylclonidine, and the G-protein inhibitor, pertussis toxin. The results suggest that the saphenous veins have a homogenous population of alpha adrenergic population (1B) which are coupled to pertussis toxin insensitive G-proteins (Table). The retrieved vein grafts show a predominantly homogenous alpha adrenergic population (1A). which are coupled to pertussis toxin sensitive G-proteins (Table). Saphenous Vein Vein Graft Phenylephrine (control) 5.04 ± 0.09 5.79 ± 0.16 * WB4101 (10 -5 M) 5.16 ± 0.33 4.73 ± 0.18 † Chloroethylclonidine (0 -5 M) 4.74 ± 0.15 # 5.38 ± 0.23 Pertussis Toxin (100 μ g/ml) 4.87 ± 0.28 4.87 ± 0.16 Mean ± s.e.m., –log 10 [EC 50 ] * p &lt; 0.05 compared to saphenous vein # p &lt; 0.05 † P &lt; 0.01 compared to phenylephrine control These results show changes both in receptor sub-type and functional coupling to G-proteins, associated with arterio-venous grafting, possibly reflecting changes in smooth muscle cell phenotype.

920-51 Indobufen Versus ASA + Dipyridamole on Coronary Artery Bypass Graft Patency: Combined Analysis of Two Multicenter Trials

Two prospective randomized double blind clinical trials, performed in United Kingdom (UK) and in Italy (IT) showed that Indobufen (INB) reversible cyclooxygenase inhibitorl is as effective as, and safer than, the association of Aspirin plus Dipyridamole in preventing the occlusion of saphenous vein (SV) coronary artery bypass grafts (CABG). The power of each of the two trials was 80% for a difference in graft occlusion of 10%. We present the results of the analysis, carried out by properly combining the information given by the two trials in order to increase the precision of the estimates both of efficacy and of safety. The analysis was performed on total 934 patients who underwent 1 year angiography (2258 SV distal anastomosis). UK and IT patients had similar clinical characteristics, UK pts had higher number of grafts per patient and smaller vessel diameters, distal anastomosis occlusion rates were 19.8% (UK) and 20.9% (IT), small vessel diameter (&lt; 1.5 mm) and right coronary artery location adversely affected graft patency in both groups. Combined analysis showed that: al the Odds Ratio of distal anastomosis occlusion of INB vs ASA + DIP group is: OR = 1.05 (95% CL: 0.85–1.291 suggesting that the efficacy of the two treatments is comparable and b) INB had significantly fewer side effects than ASA + DIP. – two multicenter CABG studies performed in different countries accruing patients with similar clinical characteristics showed similar graft patency: – combined analysis confirmed on a wide population that INB is as effective as the association of ASA + DIP on graft patency and is much better tolerated.

Effects of antiplatelet therapy with indobufen or aspirin-dipyridamole on graft patency one year after coronary artery bypass grafting

Saphenous vein coronary artery bypass graft patency can be increased by antiplatelet therapy. Aspirin plus dipyridamole are effective but are associated with tolerability problems. Indobufen is a possible alternative antiplatelet agent that may be better tolerated. A prospective, randomized, double-blind, parallel-group study was undertaken to compare the efficacy and safety of indobufen 200 mg twice daily with aspirin 300 mg thrice daily plus dipyridamole 75 mg thrice daily in preventing occlusion of autologous saphenous vein coronary artery bypass grafts. A total of 803 patients were randomized in the study, of whom 552 had a follow-up coronary angiogram approximately 1 year after operation. All anastomoses were patent in 56% of indobufen-treated patients and 59% of aspirin-dipyridamole recipients (p = 0.384). The percentage of all anastomoses patent was 82% in the indobufen group and 83% in the aspirin-dipyridamole group (p = 0.297). Mean postoperative blood loss was significantly less in the indobufen group (p = 0.043). Patients who received indobufen also had significantly fewer adverse events considered to be treatment-related compared with aspirin-dipyridamole recipients (p = 0.02). At the doses tested indobufen was as effective as aspirin plus dipyridamole in preventing occlusion of saphenous vein grafts and was better tolerated. Because indobufen was associated with less postoperative blood loss it may be used before operation in coronary artery bypass grafting.

Intraoperative electromagnetic flowmeter measurements in coronary artery bypass grafts

This study attmpts to relate flow findings in internal mammary (IMA) and saphenous vein coronary artery bypass grafts to postoperative outcome. From 262 patients undergoing coronary artery bypass grafting, 601 electromagnetic flow measurements were obtained in IMA and saphenous vein grafts, and free graft flow was measured in 227 IMAs prior to grafting. Retrograde flushing of the IMA with diluted papaverine hydrodiloride resulted in a marked increase in IMA free flow (124 ± 4 mL/min versus 66 ± 5 mL/min; p < 0.001). However, IMA free flow did not correlate with electromagnetic flow measurements after grafting to the left anterior descending coronary artery. The use of IMAs with free flows lower than 50 mL/min did not affect clinical outcome. Flow measured in saphenous vein grafts (66 ± 9 mL/min) with an electromagnetic flowmeter was significantly greater ( p < 0.001) than that in the IMA grafted on the left anterior descending coronary artery (36 ± 3 mL/min) under comparable hemodynamic conditions. For the purpose of data analysis, patients were separated into three groups based on increasing incidence of complications: levels 0,1, and 2. Patients with an uneventful outcome had a mean graft flow at chest closure of 51 ± 3 mL/min versus 51 ± 4 mL/min for patients in complication level 1 and 45 ± 11 mL/min for patients in complication level 2 ( p = not significant). Free flow measured in a vasodilated IMA was a poor predictor of flow into a grafted IMA and did not affect clinical outcome. We were unable to validate any flow limit to use of the IMA. Clinical outcome did not depend on flow measured in bypass grafts using electromagnetic flow measurements but rather was affected primarily by the preoperative clinical situation.

Angiographic predictors of a rise in serum creatine kinase (distal embolization) after balloon angioplasty of saphenous vein coronary artery bypass grafts

Distal coronary embolization is thought to be increased in the balloon angioplasty of coronary bypass vein grafts. One hundred fifty-five procedures of balloon angioplasty involving single vein graft dilatation were successfully performed. Distal coronary embolization was defined as an elevation of creatine phosphokinase greater than twice the preangioplasty value and positive MB fraction. Twenty procedures were found to have embolism by this definition. Forty preangioplasty angiograms were randomly selected from the remaining procedures and analyzed as a control group. Eight angiographic features were evaluated as possible risk factors for distal coronary embolization, i.e., diffusely diseased vein graft, presence of thrombus, ulcerated lesion surface, marked eccentricity, large plaque volume, lesion angulation, abrupt proximal face and ectasia. A diffusely diseased vein graft (p = 0.002), presence of thrombus (p = 0.006), irregular or ulcerated lesion surface (p = 0.007), large plaque volume (p = 0.02) and marked eccentricity (p = 0.03) were found to be important predictors by univariate analysis. A diffusely diseased vein graft and a large plaque volume were found to be important independent predictors by multivariate analysis. The presence of thrombus and an irregular or ulcerated lesion surface frequently coexist with a diffusely diseased vein graft. It is concluded that a diffusely diseased vein graft and a large plaque volume are important independent predictors of distal embolization, and thrombus and an ulcerated lesion surface are also important.