Thymic function is a major determinant of onset of antibody-mediated rejection in heart transplantation.

Thymic function decreases progressively with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether thymic function was related to the onset of rejection. Twenty-eight antithymocyte globulin-treated heart transplant recipients were included. Patients diagnosed for an antibody-mediated rejection on endomyocardial biopsy had a higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects. Thymus volume and density, assessed by computed tomography in a subset of patients, was also higher in patients experiencing antibody-mediated rejection. We demonstrate that thymic function is a major determinant of onset of antibody-mediated rejection and question whether thymectomy could be a prophylactic strategy to prevent alloimmune humoral responses.

Surgical site infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae after cardiac surgery: incidence and risk factors.

OBJECTIVE: To determine the incidence, microbiology and risk factors for sternal wound infection (SWI) with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) following cardiac surgery. METHODS: We performed a retrospective analysis between January 2006 and December 2015 of prospective surveillance of a cohort of patients with cardiac surgery at a single centre (Paris, France). SWI was defined as the need for reoperation due to sternal infection. All patients with an initial surgery under extracorporeal circulation and diagnosed with an SWI caused by Enterobacteriaceae isolates were included. We compared patients infected with at least one ESBL-PE with those with SWI due to other Enterobacteriaceae by logistic regression analysis. RESULTS: Of the 11 167 patients who underwent cardiac surgery, 412 (3.7%) developed SWI, among which Enterobacteriaceae were isolated in 150 patients (36.5%), including 29 ESBL-PE. The main Enterobacteriaceae (n = 171) were Escherichia coli in 49 patients (29%) and Enterobacter cloacae in 26 (15%). Risk factors for SWI with ESBL-PE in the multivariate logistic regression were previous intensive care unit admission during the preceding 6 months (adjusted odds ratio (aOR) 12.2; 95% CI 3.3-44.8), postoperative intensive care unit stay before surgery for SWI longer than 5 days (aOR 4.6; 95% CI 1.7-11.9) and being born outside France (aOR 3.2; 95% CI 1.2-8.3). CONCLUSIONS: Our results suggest that SWI due to ESBL-PE was associated with preoperative and postoperative unstable state, requiring an intensive care unit stay longer than the usual 24 or 48 postoperative hours, whereas being born outside France may indicate ESBL-PE carriage before hospital admission.

Thirteen-year experience with universal Staphylococcus aureus nasal decolonization prior to cardiac surgery: a quasi-experimental study.

INTRODUCTION: Sternal wound infection (SWI) after cardiac surgery is a severe complication. Among preventive measures, pre-operative decolonization of nasal carriage of Staphylococcus aureus has recently been shown to be beneficial. This quasi-experimental study assessed the effect of decolonization on the incidence of S. aureus-associated SWI based on 19 years of prospective surveillance. METHODS: Segmented negative binomial regression was used to analyse the change over time in the incidence of S. aureus mediastinitis requiring re-operation after cardiac surgery in a French university hospital between 1996 and 2014. Universal nasal decolonization with mupirocin was introduced in December 2001. The association between pre-operative nasal carriage and SWI due to S. aureus was analysed between 2006 and 2012. RESULTS: Among 17,261 patients who underwent a cardiac surgical procedure, 565 developed SWI (3.3%), which was caused by S. aureus in 181 cases (1%). The incidence of mediastinitis caused by S. aureus decreased significantly over the study period (1.43% in 1996-2001 vs 0.61% and 0.64% in 2002-2005 and 2006-2014, respectively; P<0.001). In segmented analysis, there was a significant break in 2002, corresponding to the introduction of decolonization. Despite this intervention, pre-operative nasal carriage remained a significant risk factor for S. aureus mediastinitis (adjusted odds ratio 2.2; 95% confidence interval 1.2-4.2), as were obesity, critical pre-operative status, coronary artery bypass grafting (CABG), and combined surgery with valve replacement and CABG. CONCLUSION: Universal nasal decolonization before cardiac surgery was effective in decreasing the incidence of mediastinitis caused by S. aureus. Nasal carriage of S. aureus remained a risk factor for S. aureus-associated SWI.

Eclipsed mitral regurgitation: an unusual cause of acute heart failure.

AIMS: So far, a total of five patients with eclipsed mitral regurgitation (MR) have been reported in the literature by three different teams. The aim of this article was to detail clinical and echocardiographic characteristics, and outcome of patients presenting eclipsed MR. METHODS AND RESULTS: We defined eclipsed MR as spontaneous appearance, at rest, from 1 min to the next of an acute restriction in the motion of mitral leaflets preventing coaptation and leading to massive MR in patients with normal left ventricular end-diastolic diameter, left ventricular ejection fraction >45%, and baseline MR ≤2. Spontaneous regression occurred within 30 min, and no obvious trigger such as acute hypertension, new-onset arrhythmia, or myocardial ischaemia is present. Clinical data, ECG, echocardiographic data, surgery report, and follow-up status of six patients with eclipsed MR are reported: all were post-menopausal women with median age of 74 [57-80] years presenting hypertension (4/6), chronic kidney disease (5/6), or chronic anaemia (4/6). Five out of six patients experienced acute pulmonary oedema requiring hospitalization and underwent mitral valve replacement because of heart failure recurrence. Two patients died in the first days after surgery while the three others are free of symptoms at, respectively, 56, 18, and 10 months follow-up. CONCLUSION: Eclipsed MR is a clinical and echocardiographic syndrome responsible for heart failure with preserved EF. It is presently underdiagnosed and should be evoked in cases of recurrent acute pulmonary oedema without obvious trigger, in particular in patients presenting discordant evaluation of MR severity over time.

[Combined heart and kidney transplantation in Fabry's disease: Long-term outcomes in two patients]. / Transplantation combinée cœur­rein au cours de la maladie de Fabry : suivi à long terme de deux patients.

INTRODUCTION: Fabry disease is a lysosomal storage disorder linked to an alpha-galactosidase A deficiency that can lead to heart and kidney failure. There is little data about the prognosis of patients who undergo a combined heart and kidney transplantation. CASE REPORTS: Two brothers who were diagnosed with Fabry disease after the age of 30 years underwent a combined heart and kidney transplantation at respectively 49 and 42 years of age because of a severe hypertrophic cardiomyopathy with end stage renal failure. They are alive respectively 4 and 9 years after the transplantation. No recurrence of the disease in the transplanted organs has been found. CONCLUSION: Combined heart and kidney transplantation in Fabry disease is an efficient therapy for the cardiomyopathy and kidney failure. Its prognosis can be good when the patients are carefully selected. However, an early diagnosis is critical in order to avoid a procedure associated with a high perioperative mortality.

Endothelin-1 in the lungs of patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is characterized by an increase in vascular tone and an abnormal proliferation of muscle cells in the walls of pulmonary arteries. Recent studies have found high plasma endothelin-1 (ET-1) concentrations in patients with PH. This study was conducted to assess whether elevated circulating ET-1 levels in PH really reflect excessive local pulmonary production. METHODS: We prospectively studied ET-1 concentration in lung specimens from 6 control subjects and 13 patients with severe PH referred for lung or heart-lung transplantation (6 patients had primary PH and 7 PH secondary to congenital heart defect). Endothelin-like immunoreactivity (ET-LI) was measured in plasma and lung tissue, using a radioimmunoassay, after ET-1 extraction. Reverse-phase high-performance liquid chromatography was also performed. RESULTS: Peripheral venous plasma ET-LI concentrations in patients with PH, whatever the cause, were greater than those in controls (10.7 +/- 0.8 vs 5.3 +/- 0.7 pg/ml; P < 0.0005). Pulmonary ET-LI was significantly higher in patients with PH, irrespective of its cause, than in controls (25.2 +/- 5.1 vs 8.1 +/- 1.1 pg/mg, P < 0.03). ET-LI pulmonary concentrations were slightly higher in Eisenmenger than in primary PH, but this was not significant (27.1 +/- 8.6 vs 22.8 +/- 5.4 pg/mg). Linear regression analysis indicated a small but significant correlation between ET-LI pulmonary concentrations and pulmonary vascular resistance in the patients with PH (r = 0.38; P = 0.047). In each case, HPLC separation of ET indicated that most of the immuno-reactivity was detected in the same fraction as ET-1. CONCLUSIONS: The striking increase in ET-1 pulmonary concentration provides new evidence that excessive local pulmonary ET-1 production may contribute to the vascular abnormalities of pulmonary hypertension.

Sternal wound infection after cardiac surgery: incidence and risk factors according to clinical presentation.

The incidence of surgical site infection (SSI) after cardiac surgery depends on the definition used. A distinction is generally made between mediastinitis, as defined by the US Centers for Disease Control and Prevention (CDC), and superficial SSI. Our objective was to decipher these entities in terms of presentation and risk factors. We performed a 7-year single centre analysis of prospective surveillance of patients with cardiac surgery via median sternotomy. SSI was defined as the need for reoperation due to infection. Among 7170 patients, 292 (4.1%) developed SSI, including 145 CDC-defined mediastinitis (CDC-positive SSI, 2.0%) and 147 superficial SSI without associated bloodstream infection (CDC-negative SSI, 2.1%). Median time to reoperation for CDC-negative SSI was 18 days (interquartile range, 14-26) and 16 (interquartile range, 11-24) for CDC-positive SSI (p 0.02). Microorganisms associated with CDC-negative SSI were mainly skin commensals (62/147, 41%) or originated in the digestive tract (62/147, 42%); only six were due to Staphylococcus aureus (4%), while CDC-positive SSI were mostly due to S. aureus (52/145, 36%) and germs from the digestive tract (52/145, 36%). Risk factors for SSI were older age, obesity, chronic obstructive bronchopneumonia, diabetes mellitus, critical preoperative state, postoperative vasopressive support, transfusion or prolonged ventilation and coronary artery bypass grafting, especially if using both internal thoracic arteries in female patients. The number of internal thoracic arteries used and factors affecting wound healing were primarily associated with CDC-negative SSI, whereas comorbidities and perioperative complications were mainly associated with CDC-positive SSI. These 2 entities differed in time to revision surgery, bacteriology and risk factors, suggesting a differing pathophysiology.

Effect of the oxidation state of LDL on the modulation of arterial vasomotor response in vitro.

Although it is established that highly oxidized LDL modify both vasodilator and vasoconstrictor responses in normal and atherosclerotic arterial tissue, there is a paucity of data on the relationship between the degree of the oxidative modification of LDL and vasomotor response. We therefore compared the impact of native LDL (Nat-LDL), and of partially (P-oxLDL), of moderately (M-oxLDL) and of highly oxidized LDL (H-oxLDL) on the vasomotor response of isolated human internal mammary artery and of rat thoracic aorta. Copper-mediated oxidative modification for up to 24 h at 37 degrees C was characterised by a progressive increase in the net negative electrical charge of LDL, and in the content of oxysterols; by contrast, lipid hydroperoxide and TBARS content peaked in M-oxLDL at 6 h. Neither basal vascular tone nor vasoconstriction induced by KCl (100 mmol/l) were modified significantly in arterial segments in relation to the degree of LDL oxidation. While Nat-LDL did not modify the contractile response of rat aorta to norepinephrine, increase in the degree of oxidative modification of LDL progressively and significantly shifted the norepinephrine response curve to the right (EC50 values for Nat-LDL, M-oxLDL and H-oxLDL: 1.2+/-0.5x10(-8), 3.5+/-1x10(-7), 1.3+/-0.4x10(-6) mol/l respectively) with reduction in the maximal effect (74.5+/-12.2 and 100.1+/-6.2% for H-oxLDL and M-oxLDL respectively, P < 0.05 versus controls). Similar findings were made in human arteries treated with H-oxLDL (P < 0.05 for EC50 and maximal response versus controls). The acetylcholine-induced, endothelial-dependent relaxation of rat aortic segments was significantly and progressively impaired with increase in the degree of LDL oxidation, maximal relaxation with H-oxLDL being 3-fold less (P < 0.05) than Nat-LDL at the same protein concentration (100 microg/ml). Acetylated LDL was without effect. Our data indicate that the increase in the degree of copper-mediated, oxidative modification of LDL parallels progressive reduction in the vasomotor response of the arterial wall to norepinephrine-induced contraction and to acetylcholine-induced relaxation subsequent to precontraction. Our data are consistent with the hypothesis that the major oxysterols (7-ketocholesterol, 7beta-hydroxycholesterol) present in Ox-LDL underlie such effects.

Plasma levels of thrombomodulin in pulmonary hypertension.

BACKGROUND: Long-standing pulmonary hypertension (PH) leads to structural alterations of the pulmonary vasculature and its endothelium, and occlusion of small vessels by microthrombi. In patients with PH, the search for factors inducing or worsening endothelium damage and in situ thrombi is still ongoing. Thrombomodulin (TM), an endothelial cell membrane protein, is a receptor for thrombin and a major anticoagulant proteoglycan. PURPOSE: To analyze plasma TM levels in patients with different forms of severe PH. PATIENTS: We prospectively studied 32 consecutive patients with PH referred for heart, lung, or heart-lung transplantation: 11 patients with primary PH (group 1), 11 patients with secondary precapillary PH (Eisenmenger's syndrome, group 2) and 10 patients with secondary postcapillary PH due to congestive heart failure (group 3). Thirty-eight healthy subjects were also studied as a control group. METHODS: Plasma concentrations of TM were measured by an immunoenzymatic technique that uses two anti-TM monoclonal antibodies that have a strong avidity and react with different epitopes of the molecule. RESULTS: Thrombomodulin plasma levels decreased in all patients with precapillary PH, and this decrease was highly significant compared with controls (26 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In primary PH, the TM decrease was only significant in males whereas in the Eisenmenger's syndrome TM values were the lowest of all the patients studied, with mean values twice as low as controls (22 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In contrast, in postcapillary PH, studied only in males, TM levels were increased (85 +/- 17 versus 54 +/- 3 ng/mL, P = 0.02). Patients with precapillary PH had more severe disease than patients with postcapillary PH, with higher pulmonary artery pressure and pulmonary vascular resistance (P < 0.001). There was no correlation between TM plasma levels and all hemodynamic variables. CONCLUSION: We found low levels of plasma TM in patients with precapillary PH but not in postcapillary PH compared with healthy controls. This may be related to the severity of PH and may contribute to the initiation or worsening of in situ thromboses frequently found in pulmonary hypertension. Further studies should analyze whether other markers of endothelial cell damage are correlated with plasma TM levels in patients with precapillary pulmonary hypertension.

Video-thoracoscopic pericardial window in the diagnosis and treatment of pericardial effusions.

Video-thoracoscopic pericardial window is a noninvasive method of pericardial drainage, allowing an excellent view of the pleural cavity and the pericardium and a precise selection of biopsy sites whether these are pericardial, pleural, lung or mediastinal. The results obtained in a series of 22 patients operated on using this technique are presented.

Pacemaker infective endocarditis.

We identified 33 patients with definite pacemaker endocarditis--that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were > or = 60 years of age (mean 66 +/- 3; range 21 to 86). Pouch hematoma or inflammation was common (58%), but other predisposing factors for endocarditis were rare. At the time that pacemaker endocarditis was found, the mean number of leads was 2.4 +/- 1.1 (range 1 to 7). The interval from the last procedure to diagnosis of endocarditis was 20 +/- 4 months (range 1 to 72). Endocarditis appeared after pacemaker implantation, early (< 3 months) in 10 patients and late (> or = 3 months) in 23 patients. Fever was the most common symptom, being isolated in 36%, associated with a poor general condition in 24%, and associated with septic shock in 9%. Transthoracic echocardiography showed vegetations in only 2 of 9 patients. Transesophageal echocardiography demonstrated the presence of lead vegetations (n = 20) or tricuspid vegetations (n = 3) in 23 of 24 patients (96%; p <0.0001 compared with transthoracic echocardiography). Pulmonary scintigraphy showed a typical pulmonary embolization in 7 of 17 patients (41%). Pathogens were mainly isolated from blood (82%) and lead (91%) cultures. The major pathogens causing pacemaker endocarditis were Staphylococcus epidermidis (n = 17) and S. aureus (n = 7). S. epidermidis was found more often in early than in late endocarditis (90% vs 50%; p = 0.05). All patients were treated with prolonged antibiotic regimens before and after electrode removal. Electrode removal was achieved by surgery (n = 29) or traction (n = 4). Associated procedures were performed in 9 patients. After the intensive care period, only 17 patients needed a new permanent pacemaker. Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88). Eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.

Long-term evaluation of a new selectively biodegradable vascular graft coated with polyethylene oxide-polylactic acid for right ventricular conduit. An experimental study.

Low-porosity woven Dacron grafts have been used extensively as an extracardiac conduit in the surgical treatment of congenital and acquired heart diseases involving total heparinization. Caution is still warranted in their use, however, because of long-term complications, including calcification and development of obstructive fibrous peel. In contrast, high-porosity grafts offer much better tissue anchorage and healing but cannot be used under heparinization. We have developed a compound vascular prosthesis in which a knitted Dacron graft is coated with a polymeric biodegradable sealant. Polyethylene oxide-polylactic acid-segmented copolymers comprised the degradable component of the graft. In vitro studies showed that the coated prosthesis exhibited a highly flexible elastomer-like mechanical response. The prostheses were completely watertight, and significant degradation started after 1 week, with absorption completed after 3 weeks. Seven woven and six knitted polyethylene oxide-polylactic acid-coated Dacron grafts used as extracordiac conduits (16 mm), connecting the right ventricle and the pulmonary artery were implanted in dogs. The dogs were killed after 12 to 18 months, and the results are reported. Scanning electron microscopy examination showed peel detachment and nonhomogenous intimal surface with fenestrations in the woven graft group, but complete healing and incorporation of the pseudointima with homogenous, thin lining of the luminal surface in the polyethylene oxide-polylactic acid-coated group. Histologic studies indicated much superior healing and anchorage of the periprosthetic tissue and the pseudointima in the polyethylene oxide-polylactic acid-coated grafts. The biodegradable polymer was fully degraded and exhibited a complete incorporation of the compound vascular prosthesis. This study indicates the superior healing properties of these selectively biodegradable grafts, which might increase long-term patency and decrease complications of right ventricular conduits.

Chronic disease of the ascending aorta. Surgical treatment and long-term results.

Between January 1979 and December 1991, we operated on 339 patients for chronic disease of the ascending aorta. The operation was elective in all. Endocarditis and its sequelae have been excluded. Thirty-one patients had a previous operation on the ascending aorta or the aortic valve; 268 patients had aneurysms of the ascending aorta without dissection; 72 had chronic aortic dissections, of whom 33 had a preexistent aneurysm. The patients included 272 men and 67 women. Mean age was 53.58 +/- 7 years. Eight percent of the patients had clinical stigmata of Marfan's disease. A tubular graft replacement was used in 7 patients, a tubular graft and valve replacement in 72 patients, and a composite valve graft replacement with reattachment of the coronary arteries using a 8 mm Dacron graft was performed in 260 patients. Concomitant procedures were used in 74 patients: coronary artery bypass grafts in 25, mitral valve replacement in 9, and aortic arch reconstruction in 40. The 30-day mortality rate was 7.6% (n = 26). For the whole group, multivariate analysis using stepwise logistic regression showed that operative risk factors were concomitant coronary artery bypass grafting, age (increased), aortic valve regurgitation, and previous cardiac surgery. Follow-up was conducted in 303 patients, and risk factors for late mortality were studied. Long-term survival was 59.6% +/- 3.7% at 9 years. It was 67% +/- 3.5% at 9 years for patients without aortic arch reconstruction and 56% +/- 4.5% for patients with aortic arch reconstruction (p = 0.0018). Reoperation was needed in 14 patients. Actuarial freedom from reoperation was 90% +/- 0.2% at 9 years for all the patients. Only one patient with composite valve graft replacement and reattachment of the coronary arteries had required reoperation for problems related to this procedure. This technique is used routinely by our team, especially in patients with large chronic aneurysms, dissected or not, and in those who had previous operations. The long-term results are good.

Recurrent left-sided heart leiomyosarcoma: should heart transplantation be legitimate?

Leiomyosarcoma of the heart is an uncommon primary malignant tumor with poor postoperative survival that may be measured in months. A leiomyosarcoma of the left atrium was diagnosed in a 47-year-old man. Initial admission was for acute pulmonary edema requiring emergency surgery. The tumor involved the left atrial cavity, and a radical resection was performed. Six months later an isolated myxomatous recurrence was detected. Heart transplantation was then performed. The patient is in good health 20 months after operation with no evidence of residual disease or recurrence. The literature has been reviewed. Surgical resection is not an adequate treatment for leiomyosarcoma of the left atrium and early heart transplantation probably offers the only hope for these patients.

Video-assisted coronary artery bypass in patients with preexisting tracheostomy.

A new technique allowing revascularization of the left coronary artery through a small thoracotomy after videoscopic harvesting of both mammary arteries is proposed in patients with total laryngectomy. This anterior thoracotomy approach, of real interest in patients with a preexisting tracheostomy, needs to be compared with a classic sternotomy in terms of functional recovery and the prevention of mediastinal sepsis in certain high-risk categories of patients (e.g., obesity, diabetes) for bilateral mammary artery harvesting.

Intraatrial insertion of a mitral prosthesis in a destroyed or calcified mitral annulus.

Infectious lesions and extreme calcification of the mitral valve annulus can make classic anatomic implantation of a prosthesis impossible. Confronted with these circumstances, we have developed a technique of intraatrial insertion of a mitral prosthesis. The prosthesis has been modified by enlarging the circumference of the sewing ring with a Dacron collar. The collar can be sutured to the left atrial wall above the mitral annulus. From 1981 to 1989, this technique has been employed in 36 patients: 15 had acute valve endocarditis with destruction of the mitral annulus and 21 had extensive annular calcification. In all cases, circumferential or partial intraatrial insertion permitted a secure implantation of the prosthesis. One operative death was related to the technique. It was an intractable bleeding caused by tearing of the very thin and fragile wall of the left atrium in a kidney transplant patient. Four patients were reoperated on for periprosthetic leak, in 3 of whom healing and cleaning of the mitral annulus permitted annular implantation of a prosthetic valve. There was no ventricular wall rupture. Our results suggest that the technique can be performed in high operative risk patients when mitral valve replacement is impossible by conventional techniques.

Myocardial protection by blood cardioplegia and warm reperfusion in heart transplantation.

We describe the technique of blood cardioplegia delivery as we routinely use it in clinical heart transplantation. This technique needs a specific circuit. Perfusion of a first dose of blood cardioplegia is immediately started on the arrival of the graft in the operating room. Cardiac reperfusion of a half-dose of blood solution without potassium is performed each 20 minutes. Myocardial warm reperfusion is started at the end of the aortic suture. This technique of blood cardioplegia and warm reperfusion during heart transplantation provided an improvement in heart preservation when compared with standard crystalloid solution.

Thoracoscopic internal mammary artery harvesting: technical considerations.

BACKGROUND: Technical details of thoracoscopic harvesting of the internal mammary artery (IMA) are reported. This procedure allows a complete dissection of the left IMA from its origin at the subclavian artery to the sixth intercostal branches with transection of all collateral branches. METHODS: Between September 1995 and September 1996, thoracoscopic harvesting of the left IMA was performed on 32 patients who had undergone a minimally invasive coronary artery bypass grafting procedure. RESULTS: There were no conversions to a standard approach because of an injury to the graft and no reoperations for bleeding. The mean duration of the IMA harvesting procedure was 58.7 minutes (range, 20 to 130 minutes). CONCLUSIONS: This procedure enlarges the field of minimally invasive coronary artery bypass grafting techniques. The thoracoscopic harvest of the full length of the IMA allows the procedure to more closely replicate the open approach.

Facilitated vascular anastomoses: the one-shot device.

BACKGROUND: A mechanical system for facilitating vascular anastomosis (end-to-side, end-to-end) is described that enables the rapid construction of nonpenetrated, compliant junctions. The instrument (United States Surgical One-Shot system) simultaneously applies either 10 or 12 nonpenetrating, arcuate-legged titanium clips to everted vessel or prosthetic conduit edges. METHODS AND RESULTS: The instrument has been tested in animals (jugular and femoral vein jump grafts in carotid and femoral arteries, interpositional grafts, 20 pigs) and human cadaveric constructs (saphenous veins to left anterior descending coronary arteries, 20 cases, 5 brachiocephalic access fistulas) as end-to-side constructs. Clipped constructs have equivalent or superior physical properties to control sutured constructs (6-0 polypropylene) as gauged by burst and tensile strength. All studies were performed under Food and Drug Administration Good Laboratory Practice standards, and the device has been approved for marketing by the Food and Drug Administration. CONCLUSIONS: The device enables rapid and reproducible vascular anastomotic constructs with vessels as small as 1.8 mm outer diameter. The constructs are flanged, interrupted, and nonpenetrated.