Expression of vascular endothelial growth factor in aortocoronary saphenous vein bypass grafts.

Neovascularisation is a prominent feature of long-term aortocoronary saphenous vein bypass grafts but mechanisms involved in the formation of neovessels have not been previously studied. Vascular Endothelial Growth Factor (VEGF) is an important angiogenic factor that induces migration and proliferation of endothelial cells, enhances permeability and modulates thrombogenecity. This study investigated the expression of VEGF in aortocoronary saphenous vein bypass grafts. Aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of >75% were explanted from 14 patients at redo coronary artery bypass grafting. The grafts demonstrated two distinct forms of graft occlusion: four out of the 14 graft occlusions (29%) resulted from severe hyperplastic transformation of the intima complicated by thrombi attached to the degenerating liminal endothelium; the remaining graft occlusions (71%) were due to the development of atherosclerotic lesions associated with mural thrombosis. Hiperplastically altered intimal segments were practically free of neovascularisation while atherosclerotic-like lesions contained neovessels irregularly distributed throughout. Intimal neovessels were located exclusively in microzones enriched with VEGF-expressing cells and, furthermore, neovascular endothelial cells themselves also displayed VEGF immunopositivity. Double-immunostaining revealed that in areas of neovascularisation, the vast majority macrophages (CD68+) expressed VEGF. Some CD68+ foam cells that surrounded branches of neovascularisation were also VEGF-positive. These findings suggest that VEGF expressed by neovascular endothelial cells and by macrophages may act as a local regulator of endothelial cells functions and may induce intimal neovascularisation in aortocoronary saphenous vein bypass grafts affected by atherosclerosis.

Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts.

This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.

Immunohistochemical and ultrastructural evidence that dendritic cells infiltrate stenotic aortocoronary saphenous vein bypass grafts.

We earlier speculated that antigen-presenting dendritic cells may be involved in the immune reactions leading to saphenous vein bypass graft failure. The purpose of this study was to confirm whether dendritic cells are present in stenotic human saphenous vein bypass grafts. Segments of stenotic saphenous vein grafts were explanted from 14 patients at re-do bypass operation and ten normal saphenous veins were harvested during femoro-popliteal grafting. Sections of specimens were analysed using cell type specific antibodies to identify dendritic cells (CD1a, S-100), T-lymphocytes (CD3), macrophages (CD68), smooth muscle cells (alpha-SMA) and endothelial cells (FVIII). Dual immunostaining, confocal immunofluorescent laser scanning microscopy and electron microscopy were used. Stenotic grafts showed structural alterations of intimal hyperplasia and varying degrees of atherosclerotic degeneration. No cells expressing CD1a and S-100 were observed in the intima and media of normal saphenous veins. Cells expressing these antigens were present around areas of medial neovascularization and within intimal atherosclerotic lesions in saphenous vein bypass grafts. Electron microscopy demonstrated the presence of cells containing a well-developed tubulovesicular system which is unique to cells from the dendritic cell family. Double immunohistochemistry and confocal immunofluorescent microscopy revealed the co-localization of T-lymphocytes with dendritic cells. Dendritic cells are present in stenotic saphenous vein bypass grafts. Dendritic cells may be responsible for antigen presentation and modulation of immune reactions in accelerated graft atherosclerosis through their interaction with T-lymphocytes.

Electron-microscopic detection of apoptotic and necrotic cell death in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.

Aortocoronary saphenous vein bypass grafts undergo structural alterations within the arterialized vein, resulting in graft stenosis and failure. Areas of the acellular intima contribute to fissuring, cracking and ulceration, while areas of the media become highly vascular but thinned. This study aimed to examine the ultrastructural features of cell death, including apoptosis and necrosis, in non-atherosclerotic areas of the stenotic aortocoronary saphenous vein bypass grafts. Thirteen stenotic vein grafts were obtained at redo coronary artery bypass grafting. The ultrastructural features of cell death were analysed by electron microscopy. Typical features of necrosis, including focal areas of cytoplasmic oedema, plasmalemmal destruction and nuclear condensation with cytoplasmic organelle destruction, were observed throughout the intima and media. Features of apoptosis, including the presence of apoptotic bodies, were also identified in the hyperplastic intima and its adjacent media. Our observations suggest that both apoptosis and necrosis occur in non-atherosclerotic areas of stenotic aortocoronary saphenous vein bypass grafts.

Dendritic cells in aortocoronary saphenous vein bypass grafts.

Dendritic cells are specialised leucocytes responsible for capturing and presenting antigens to T lymphocytes, which in turn mediate immune responses in various pathological conditions. The observations in this study demonstrate that dendritic cells are present in stenotic aortocoronary saphenous vein bypass grafts, which suggest that these cells may be involved in inflammatory actions which may subsequently contribute to 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 > 75%) were harvested from 10 patients (nine male, one female), aged 4271 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 alpha-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-10O-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-positve 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.

Structural features of cell death in atherosclerotic lesions affecting long-term aortocoronary saphenous vein bypass grafts.

Aortocoronary saphenous vein bypass grafts fail because of structural pathologies (thrombosis, intimal hyperplasia and atherosclerosis) within the 'arterialized' vein leading to graft stenosis. This study examined structural characteristics of atherosclerotic alterations in long-term aortocoronary artery saphenous vein bypass grafts with particular attention to the features of cell death in atherosclerotic lesions. Stenotic vein grafts were obtained from 10 patients at redo coronary artery bypass grafting operations. All the grafts were affected by histological abnormalities, with eight out of ten grafts showing evidence of atherosclerotic alterations in the intimal hyperplastic layer. Areas containing foam cells were examined by electron microscopy. Cells with cytoplasmic lipid accumulations were characterized by varying degrees of chromatin condensation, fragmentation or dispersion, by focal areas of oedema and vacuolisation of their cytoplasm, and by plasmalemmal destruction. Some lipid-filled cells exhibiting signs of destruction contained myofilaments and basal membrane fragments, allowing them to be identified as smooth muscle cells. Macrophage foam cells were found to have undergone similar destruction. No cells showing nuclear degeneration were observed to have intact cytoplasmic organelles. Neither were apoptotic bodies identified, but necrotic remnants were frequently seen. The results suggest that cell death in atherosclerotic lesions affecting aortocoronary artery saphenous vein bypass grafts occurs through oncosis rather than by apoptosis.

Left atrial reduction for chronic atrial fibrillation associated with mitral valve disease.

Currently available surgical procedures to control chronic atrial fibrillation associated with mitral valvar disease are not always successful. The size of the left atrium is a major factor in the initiation and maintenance of atrial fibrillation. Here we describe a case of ablation of atrial fibrillation with left atrial reduction and pulmonary vein isolation in a patient with mitral valve disease.

Papaverive abolishes endothelium-dependent dilatation of human internal mammary arteries in vitro.

1. The purpose of the present study was to examine the effects of papaverine-HCl, administered into the lumen of the human internal mammary artery (IMA) during harvesting of this vessel, on vascular reactivity in vitro and to specifically test the hypothesis that intraluminal administration of papaverine-HCl impairs endothelium-dependent vasodilation. 2. The present study measured in vitro dilator and constrictor responses of terminal segments of human IMA. Internal mammary artery segments were obtained either prior to routine administration of intraluminal papaverine (pre-P) or after papaverine administration (post-P) in patients undergoing coronary artery bypass grafting. In addition, the viability of cultured human saphenous vein endothelial cells exposed to papaverine-HCl was examined. 3. Cumulative concentrations of U46619, 5-hydroxytryptamine and phenylephrine (PE) produced active contractions in post-P IMA rings. Contractile responses to low concentrations of endothelin-1 were significantly enhanced in post-PIMA compared with pre-P IMA segments. 4. Maximal endothelium-dependent vasodilator responses of pre-P IMA segments to cumulative concentrations of acetylcholine (ACh) and the calcium ionophore A23187 were 49 +/- 7 and 66 +/- 4%, respectively, of the initial active tension induced by PE (1 mumol/L). 5. Maximal endothelium-dependent vasodilator responses were markedly attenuated in post-P IMA (6 +/- 6 and 11 +/- 10% for ACh and A23187, respectively; P < 0.0001 for both vasodilators compared with pre-P). Post-P IMA relaxed completely to the endothelium-independent vasodilator sodium nitroprusside. 6. Exposure of cultured human saphenous vein endothelial cells to papaverine-HCl (1.2 and 12.0 mg/mL) for 1 h resulted in the reduced viability of these cells. 7. The loss of endothelium-dependent relaxation could dangerously predispose the IMA graft to vasospasm in the postoperative period.

Homograft aortic root replacement for destructive prosthetic endocarditis.

Prosthetic aortic valve endocarditis with extensive destruction of the aortic root, annular abscess formation, and left ventriculoaortic discontinuity was seen in 3 patients, with aorta to left atrial fistula formation in 2. Homograft aortic root replacement with use of the anterior mitral leaflet of the aortic root to repair the fistula was used successfully in all 3 patients. Their case reports are discussed to highlight the use of the homograft aortic root in these complicated cases, and to report the occurrence of aorto-left atrial fistula in prosthetic valve endocarditis.

Right ventricular assist and prostacyclin infusion for allograft failure in the presence of high pulmonary vascular resistance.

The presence of high pulmonary vascular resistance (PVR) greater than 4 Wood units contributes to significant early posttransplant mortality, and remains a negative predictor of long-term survival. Current trends have been toward exclusion of the recipient with high PVR from the orthotopic procedure; elective heterotopic allograft placement is increasingly advocated. A patient with a PVR of 6 Wood units underwent orthotopic transplantation; the cardiac allograft from a 12 kg heavier donor was implanted after an ischemic time of 115 minutes. Early graft failure at 4 hours and subsequent cardiac arrest were followed by reinstitution of cardiopulmonary bypass, during which time optimal pharmacologic manipulation of the pulmonary vasculature was undertaken, including the use of high-dose prostacyclin. Refractory right heart failure indicated the requirement for right ventricular assistance (RVA) for patient survival. RVA with a Bio-Medicus pump was instituted in association with high-dose prostacyclin; an intraaortic balloon pump was inserted 12 hours later. Maintenance immunosuppression consisted of cyclosporine and azathioprine alone. RVA was maintained for 3 days; during this time the patient was totally pump dependent. Over an 18-hour period the patient was weaned and successfully withdrawn from RVA. Intraaortic balloon pump counterpulsation and the prostacyclin infusion were continued for 6 and 10 days, respectively. The clinical implications of the various interventions that resulted in the patient's survival are discussed.

Ascending aortic aneurysms associated with aortic valve regurgitation: St Vincent's Hospital's experience.

This report represents a retrospective analysis of the St Vincent's Hospital experience with combined replacement of the aortic valve and ascending aorta using a composite conduit and coronary artery reimplantation, in 44 patients, from 1 January 1981 to 30 June 1988. The mean age at operation was 48 years. Annuloaortic ectasia was the most common indication for operation in 24 patients (54%). There were three hospital deaths (7%). Forty-one patients were discharged from hospital and were followed up for a total of 1,106 patient months (mean = 26.5 months). There were three late deaths (7%). One death was due to a new dissection, one to a cerebrovascular accident and one to a drug overdose. So far, no patients have required reoperation. Of the 36 surviving patients available for follow-up, 28 are in New York Heart Association class I, seven patients are in class II and one in class III. Composite graft replacement reduces the risk of recurrent dissection and aneurysm formation and of periprosthetic leak. In the present experience, it is the method of choice in patients with degenerative lesions in the ascending aorta and aortic valve and particularly for annuloaortic ectasia. The exact surgical technique currently used has been the result of an evolution of different techniques.

Repeat myocardial revascularization surgery: an analysis of 169 cases.

One hundred and sixty-nine patients who underwent repeated myocardial revascularization surgery between 1982 and 1987 were studied. The mean interval between operations was 91.6 +/- 7.3 months. The indications for repeated surgery were graft failure in 37.2% of patients, progressive coronary atherosclerosis in 40.2% of patients and a combination of the two causes in 22.5% of patients. The mean number of grafts that were inserted was 2.74 +/- 0.61 grafts per patient at the second operation. Coronary endarterectomy as an adjunctive procedure was necessary in 17.1% of patients. The hospital mortality rate was 4.1%, with a 1.8% incidence of perioperative myocardial infarctions. Of the surviving patients, 96.3% were available for follow-up at a mean of 19 +/- 6.4 months. Of these patients, 68.5% were well and could be categorized into the New York Heart Association's functional class I. We conclude that both progression of coronary atherosclerosis in native vessels and obstruction of venous grafts cause recurrent angina and that repeated myocardial revascularization surgery is a feasible treatment option in these patients.

Open cardiac compression in the postoperative cardiac intensive care unit.

Thirty-nine patients required heroic resuscitative measures for sudden hypotension and cardiac arrest in the first 72 hours following cardiac surgery between January 1, 1984 and May 31, 1988. Emergency sternotomy with open cardiac compression was performed in twenty-four of these patients when external cardiac compression failed. These were categorised as Group A. Group B comprised the fifteen patients in whom resuscitation was entirely by means of external compression and adjuvant measures. Survival with NYHA Functional Class I and II status was noted in 75% of patients in Group A, compared with 20% in Group B (P less than 0.002). Emergency sternotomy with open cardiac compression is an effective way of resuscitating patients in the intensive care unit in the first few days following open heart surgery.

Homograft aortic root replacement to correct infective endocarditis requiring seven open cardiac procedures.

Infective endocarditis, presumably from a septic dental focus, affecting the aortic valve was seen as acute aortic regurgitation in a 20-year-old woman. Seven open cardiac procedures for replacement of the aortic valve and left ventricular outflow tract were performed over the subsequent 6 years. Aortic root replacement using a fresh antibiotic-sterilized homograft was performed as the last definitive operative procedure. This article is presented to highlight (1) the use of homograft aortic root replacement for extensive involvement of aortic valve and left ventricular outflow tract in cases of infective endocarditis and (2) the feasibility of multiple sternal reentries when indicated.

The Bentall procedure: a surgical option in Ehlers-Danlos syndrome.

The Ehlers-Danlos syndrome (EDs) is one of the most frequently encountered inherited disorders of connective tissue. The arterial-ecchymotic type IV is notorious for large vessel involvement associated with spontaneous catastrophic bleeding. Most of these patients who require cardiovascular surgical procedures have a poor prognosis. Our experience of two patients, with aneurysmal dilatation of the ascending aorta is presented. The first patient presented with an aortic dissection extending from the ascending aorta to the common iliac arteries. The second patient presented with asymptomatic but progressive aneurysmal dilatation of the aortic root. Both patients underwent the Bentall procedure using a 25 mm St. Jude composite valved conduit. Despite increased vascular friability, both of these patients tolerated the operative procedure without complication and are doing well on early follow-up. This experience suggests that the Bentall procedure may be used to decrease the risks of dissection and rupture of the ascending aorta in patients with Ehlers-Danlos syndrome.