Central artery stiffness and thoracic aortopathy.

Thoracic aortopathy, especially aneurysm, dissection, and rupture, is responsible for significant morbidity and mortality. Uncontrolled hypertension and aging are primary risk factors for such conditions, and they contribute to an increase in the mechanical stress on the wall and an increase in its structural vulnerability, respectively. Select genetic mutations also predispose to these lethal conditions, and the collection of known mutations suggests that dysfunctional mechanosensing and mechanoregulation of the extracellular matrix may contribute to pathogenesis and disease progression. In the absence of a well-accepted pharmacotherapy, nonsurgical treatments tend to focus on reducing the mechanical loading on the aorta, particularly via the use of antihypertensive medications and recommendations to avoid strenuous exercises such as weight lifting. In this brief review, we discuss the important effects of central artery stiffening on global hemodynamics and, in particular, on the increase in pulse pressure that acts on the proximal thoracic aorta. We consider Marfan syndrome as an illustrative aortopathy but discuss other conditions leading to thoracic aortic aneurysm and dissection. We highlight the importance of phenotyping the aorta biomechanically, not just clinically, and emphasize the utility of mouse models in elucidating molecular and mechanical mechanisms of disease. Notwithstanding the widely recognized role of central artery stiffening in driving end-organ disease, we suggest that there is similarly a need to consider its key role in thoracic aortopathy.

Biomechanical Phenotyping of the Murine Aorta: What Is the Best Control?

The availability of diverse mouse models is revealing increasingly greater information on arterial mechanics, including homeostatic adaptations and pathologic maladaptations to genetic, pharmacological, and surgical manipulations. Fundamental to understanding such biomechanical changes, however, is reliable information on appropriate control vessels. In this paper, we contrast 15 different geometrical and mechanical metrics of biaxial wall mechanics for the ascending aorta across seven different types of possible control mice. We show that there is a comforting similarity across these multiple controls for most, though not all, metrics. In particular, three potential controls, namely, noninduced conditional mice, exhibit higher values of distensibility, an important clinical metric of structural stiffness, and two of these potential controls also have higher values of intrinsic circumferential material stiffness. There is motivation, therefore, to understand better the biomechanical changes that can arise with noninduced Cre-lox or similar approaches for generating mutations conditionally. In cases of germline mutations generated by breeding heterozygous +/- mice, however, the resulting homozygous +/+ mice tend to exhibit properties similar to traditional (C57BL/6) controls.

Complement C5 Inhibition Reduces T Cell-Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice.

Allograft vasculopathy (AV) is characterized by diffuse stenoses in the vasculature of solid organ transplants. Previously, we developed two humanized models showing that alloantibody and ischemia reperfusion injury (IRI) exacerbated T cell-mediated AV in human arterial xenografts in vivo. Herein we examined a causal role for terminal complement activation in both settings. IRI, in contrast to alloantibody, elicited widespread membrane attack complex (MAC) assembly throughout the vessel wall. Both alloantibody and IRI caused early (24 h) and robust endothelial cell (EC) activation localized to regions of intimal MAC deposition, indicated by increases in nuclear factor kappa B (NF-κB)-inducing kinase, an MAC-dependent activator of noncanonical NF-kB, VCAM-1 expression and Gr-1+ neutrophil infiltration. Endothelial cell activation by alloantibody was inhibited by antimouse C5 mAb, but not by anti-C5a mAb or by control mAb, implicating MAC as the primary target of anti-C5 mAb. Antimouse C5 mAb significantly reduced alloantibody- and IRI-enhanced T cell infiltration and AV-like changes, including neointimal hyperplasia as well as intraluminal thrombosis in a subset of IRI-treated arterial grafts. These results indicate that increased AV lesion formation in response to either alloantibody or IRI is dependent on complement C5 activation and, accordingly, inhibition of this pathway may attenuate AV.

Transforming growth factor beta expression by human vascular cells inhibits interferon gamma production and arterial media injury by alloreactive memory T cells.

Arteriosclerosis is characterized by the local activation of effector T cells leading to production of proinflammatory cytokines, such as IFN (interferon)-γ and IL-17, within the vessel wall. Conversely, the production of antiinflammatory cytokines, for example, TGF-ß, by regulatory lymphocytes is known to inhibit both the differentiation of naïve T cells into effector T cells and the development of arteriosclerosis in murine models. We investigated the role of TGF-ß on the alloreactivity of human effector memory T cells (Tem). Quiescent vascular cells, but not Tem, expressed TGF-ß. Blockade of TGF-ß activity in cocultures of CD4(+) Tem with allogeneic endothelial cells significantly increased IFN-γ, but not IL-17, secretion. Additionally, serologic neutralization of TGF-ß in immunodeficient mouse hosts of human coronary artery grafts into which allogeneic human T cells were adoptively transferred resulted in heavier medial infiltration by Tem, greater loss of medial smooth muscle cells and increased IFN-γ production within the grafts without significantly reducing either intimal injury or IL-17 production. Protective effects of TGF-ß may be limited by fewer TGF-ß-expressing vascular cells within the intimal compartment, by a reduction in the expression of TGF-ß by vascular cells in rejecting grafts, or possibly to less effective suppression of Tem than naïve T cells.

Adventitial remodeling protects against aortic rupture following late smooth muscle-specific disruption of TGFß signaling.

Altered signaling through transforming growth factor-beta (TGFß) increases the risk of aortic dissection in patients, which has been confirmed in mouse models. It is well known that altered TGFß signaling affects matrix turnover, but there has not been a careful examination of associated changes in structure-function relations. In this paper, we present new findings on the rupture potential of the aortic wall following late postnatal smooth muscle cell (SMC)-specific disruption of type I and II TGFß receptors in a mouse model with demonstrated dissection susceptibility. Using a combination of custom computer-controlled biaxial tests and quantitative histology and immunohistochemistry, we found that loss of TGFß signaling in SMCs compromises medial properties but induces compensatory changes in the adventitia that preserve wall strength above that which is needed to resist in vivo values of wall stress. These findings emphasize the different structural defects that lead to aortic dissection and rupture - compromised medial integrity and insufficient adventitial strength, respectively. Relative differences in these two defects, in an individual subject at a particular time, likely reflects the considerable phenotypic diversity that is common in clinical presentations of thoracic aortic dissection and rupture. There is, therefore, a need to move beyond examinations of bulk biological assays and wall properties to cell- and layer-specific studies that delineate pathologic and compensatory changes in wall biology and composition, and thus the structural integrity of the aortic wall that can dictate differences between life and death.

TNF receptors differentially signal and are differentially expressed and regulated in the human heart.

Tumor necrosis factor (TNF) utilizes two receptors, TNFR1 and 2, to initiate target cell responses. We assessed expression of TNF, TNFRs and downstream kinases in cardiac allografts, and compared TNF responses in heart organ cultures from wild-type ((WT)C57BL/6), TNFR1-knockout ((KO)), TNFR2(KO), TNFR1/2(KO) mice. In nonrejecting human heart TNFR1 was strongly expressed coincidentally with inactive apoptosis signal-regulating kinase-1 (ASK1) in cardiomyocytes (CM) and vascular endothelial cells (VEC). TNFR2 was expressed only in VEC. Low levels of TNF localized to microvessels. Rejecting cardiac allografts showed increased TNF in microvessels, diminished TNFR1, activation of ASK1, upregulated TNFR2 co-expressed with activated endothelial/epithelial tyrosine kinase (Etk), increased apoptosis and cell cycle entry in CM. Neither TNFR was expressed significantly by cardiac fibroblasts. In (WT)C57BL/6 myocardium, TNF activated both ASK1 and Etk, and increased both apoptosis and cell cycle entry. TNF-treated TNFR1(KO) myocardium showed little ASK1 activation and apoptosis but increased Etk activation and cell cycle entry, while TNFR2(KO) myocardium showed little Etk activation and cell cycle entry but increased ASK1 activation and apoptosis. These observations demonstrate independent regulation and differential functions of TNFRs in myocardium, consistent with TNFR1-mediated cell death and TNFR2-mediated repair.

Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo.

This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk observation period and allowed noninvasive MR imaging of the human TEVGs for real-time, serial monitoring of hASMC retention. This study demonstrates the feasibility of applying noninvasive imaging techniques for evaluation of in vivo TEVG performance.

Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences.

Aging leads to central artery stiffening and associated hemodynamic sequelae. Because healthy arteries exhibit differential geometry, composition, and mechanical behaviors along the central vasculature, we sought to determine whether wall structure and mechanical function differ across five vascular regions-the ascending and descending thoracic aorta, suprarenal and infrarenal abdominal aorta, and common carotid artery-in 20 versus 100-week-old male wild-type mice. Notwithstanding generally consistent changes across these regions, including a marked thickening of the arterial wall, diminished in vivo axial stretch, and loss of elastic energy storage capacity, the degree of changes tended to be slightly greater in abdominal than in thoracic or carotid vessels. Likely due to the long half-life of vascular elastin, most mechanical changes in the arterial wall resulted largely from a distributed increase in collagen, including thicker fibers in the media, and localized increases in glycosaminoglycans. Changes within the central arteries associated with significant increases in central pulse pressure and adverse changes in the left ventricle, including increased cardiac mass and decreased diastolic function. Given the similar half-life of vascular elastin in mice and humans but very different life-spans, there are important differences in the aging of central vessels across these species. Nevertheless, the common finding of aberrant matrix remodeling contributing to a compromised mechanical homeostasis suggests that studies of central artery aging in the mouse can provide insight into mechanisms and treatment strategies for the many adverse effects of vascular aging in humans.

Hemodynamics-driven deposition of intraluminal thrombus in abdominal aortic aneurysms.

Accumulating evidence suggests that intraluminal thrombus plays many roles in the natural history of abdominal aortic aneurysms. There is, therefore, a pressing need for computational models that can describe and predict the initiation and progression of thrombus in aneurysms. In this paper, we introduce a phenomenological metric for thrombus deposition potential and use hemodynamic simulations based on medical images from 6 patients to identify best-fit values of the 2 key model parameters. We then introduce a shape optimization method to predict the associated radial growth of the thrombus into the lumen based on the expectation that thrombus initiation will create a thrombogenic surface, which in turn will promote growth until increasing hemodynamically induced frictional forces prevent any further cell or protein deposition. Comparisons between predicted and actual intraluminal thrombus in the 6 patient-specific aneurysms suggest that this phenomenological description provides a good first estimate of thrombus deposition. We submit further that, because the biologically active region of the thrombus appears to be confined to a thin luminal layer, predictions of morphology alone may be sufficient to inform fluid-solid-growth models of aneurysmal growth and remodeling.

Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms.

Thoracic aortic aneurysms are life-threatening lesions that afflict young and old individuals alike. They frequently associate with genetic mutations and are characterized by reduced elastic fibre integrity, dysfunctional smooth muscle cells, improperly remodelled collagen and pooled mucoid material. There is a pressing need to understand better the compromised structural integrity of the aorta that results from these genetic mutations and renders the wall vulnerable to dilatation, dissection or rupture. In this paper, we compare the biaxial mechanical properties of the ascending aorta from 10 murine models: wild-type controls, acute elastase-treated, and eight models with genetic mutations affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal proteins, or intracellular signalling molecules. Collectively, our data for these diverse mouse models suggest that reduced mechanical functionality, as indicated by a decreased elastic energy storage capability or reduced distensibility, does not predispose to aneurysms. Rather, despite normal or lower than normal circumferential and axial wall stresses, it appears that intramural cells in the ascending aorta of mice prone to aneurysms are unable to maintain or restore the intrinsic circumferential material stiffness, which may render the wall biomechanically vulnerable to continued dilatation and possible rupture. This finding is consistent with an underlying dysfunctional mechanosensing or mechanoregulation of the extracellular matrix, which normally endows the wall with both appropriate compliance and sufficient strength.

Loss of Elastic Fiber Integrity Compromises Common Carotid Artery Function: Implications for Vascular Aging.

Competent elastic fibers endow central arteries with the compliance and resilience that are fundamental to their primary mechanical function in vertebrates. That is, by enabling elastic energy to be stored in the arterial wall during systole and then to be used to work on the blood during diastole, elastic fibers decrease ventricular workload and augment blood flow in pulsatile systems. Indeed, because elastic fibers are formed during development and stretched during somatic growth, their continual tendency to recoil contributes to the undulation of the stiffer collagen fibers, which facilitates further the overall compliance of the wall under physiologic pressures while allowing the collagen to limit over-distension during acute increases in blood pressure. In this paper, we use consistent methods of measurement and quantification to compare the biaxial material stiffness, structural stiffness, and energy storage capacity of murine common carotid arteries having graded degrees of elastic fiber integrity - normal, elastin-deficient, fibrillin-1 deficient, fibulin-5 null, and elastase-treated. The finding that the intrinsic material stiffness tends to be maintained nearly constant suggests that intramural cells seek to maintain a favorable micromechanical environment in which to function. Nevertheless, a loss of elastic energy storage capability due to the loss of elastic fiber integrity severely compromises the primary function of these central arteries.

Human allogeneic vascular rejection after arterial transplantation and peripheral lymphoid reconstitution in severe combined immunodeficient mice.

BACKGROUND: Interspecies differences create important shortcomings in existing animal models used to describe in vivo events responsible for allograft rejection. Alloimmune destruction of human dermal microvessels, histologically consistent with rejection, has been demonstrated in human skin-grafted severe combined immunodeficient (SCID) mice receiving allogeneic human peripheral blood mononuclear cells (PBMC). We have now documented human alloimmune injury in a vascularized, SCID-human arterial transplantation model. METHODS: Fresh human artery was used to replace the CB.17 SCID/beige mouse infrarenal aorta. Seven days later, 3x10(8) human PBMC were administered intraperitoneally, and lymphocyte engraftment was considered successful when circulating human CD3+ cells were later identified in peripheral blood. RESULTS: Forty-six of 49 (94%) mice undergoing transplantation survived, including 14 controls with arterial grafts receiving no PBMC. Twenty-eight of 32 mice demonstrated circulating human CD3+ cells, 14 days after PBMC administration. Animals were killed at 14, 21, or 28 days after receiving allogeneic PBMC, and arteries were recovered for histology and immunohistology. All 14 control mice had patent transplanted grafts with normal vascular histology and no lymphoid infiltration. Damage to transplanted arteries among lymphocyte-engrafted mice was apparent by 14 and 21 days in some animals, whereas 16 of 22 exhibited moderate to severe intimal, medial, and/or adventitial lymphocytic infiltration with intimal expansion by day 28. The infiltrate consisted of HLA-A, -B, -C+, and -DR+, human CD3+ cells, approximately equally distributed as CD4+ and CD8+ subsets. Some infiltrating lymphocytes were cytolytic cells as demonstrated by perforin staining. The endothelium of transplanted human arteries exhibited endothelialitis, and the endothelial cells stained intensely with anti-HLA-A, -B, -C and anti-HLA-DR antibodies. The expanded intima was predominantly smooth muscle cells, staining positively for smooth muscle alpha-actin, HLA-A, -B, -C and HLA-DR. Medial necrosis was not observed. CONCLUSION: The results provide evidence of alloimmune-mediated vascular rejection in this human arterial transplantation model.

Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts.

BACKGROUND: We have previously demonstrated that human artery grafts transplanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porcine xenoresponses in this model. METHODS: Pig coronary artery segments were interposed into the infrarenal aorta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes and/or treated with proinflammatory cytokines. The grafts were harvested after 1-70 days and examined by histology, immunohistochemistry, and morphometry. RESULTS: Pig artery grafts from untreated mice had no evidence of injury, leukocytic infiltrate, or endothelial cell activation up to 70 days postoperatively, despite deposition of murine complement. Host reconstitution with human peripheral blood mononuclear cells resulted in a discrete population of circulating T cells that did not infiltrate or injure the grafts up to 28 days after adoptive transfer. Administration of porcine interferon-gamma for up to 28 days sustained the expression of graft vascular cell adhesion molecule-1 and major histocompatibility complex antigens, but did not initiate recruitment of human leukocytes. In contrast, treatment with human tumor necrosis factor for 7 days induced the de novo expression of porcine E-selectin by graft endothelial cells and elicited human T cell infiltration and human peripheral blood mononuclear cell-dependent vascular injury. CONCLUSIONS: The human peripheral blood mononuclear cell-severe combined immunodeficiency/beige mouse model identifies a significant difference between human T cell allogeneic and xenogeneic responses in vivo. Xenografts with quiescent endothelium are not infiltrated or injured by T cells under the same conditions in which allografts are rejected. Activation of pig coronary artery endothelial cells by human tumor necrosis factor, but not porcine interferon-gamma, elicits cellular xenoresponses.

Effect of left ventricular volume on results of coronary artery bypass grafting.

After coronary artery bypass grafting, our patients with ischemic cardiomyopathy and significant left ventricular (LV) dilation demonstrated an improvement in angina symptoms, acceptable operative and medium-term survival, a trend toward improvement in LV ejection fraction, and a significant reduction in LV chamber size. Our results suggest that patients with ischemic cardiomyopathy and LV dilation should not be excluded from surgical revascularization based on ventricular size alone.

Retrosternal ileocolic esophageal replacement in children revisited. Antireflux role of the ileocecal valve.

The risk of postoperative reflux and pulmonary aspiration with straight colon or gastric tube esophageal replacement in children prompted us to reevaluate the presumed antireflux role of the ileocecal valve with retrosternal ileocolic interposition. This operation was done in eight patients with esophageal atresia (six) and lye stricture (two) from 19 to 50 months of age between 1983 and 1992. There were no operative deaths. The duration of follow-up ranged from 4 to 115 months. Barium swallow obtained in all patients showed unobstructed esophagoileocolic transit without reflux. Two patients with esophageal atresia had localized proximal anastomotic leaks, which healed spontaneously without stricture. In the two patients with lye ingestion ileoesophageal strictures developed that necessitated revision. None of the patients had postoperative respiratory complications or symptomatic gastroesophageal reflux. All eight children have had their gastrostomy tubes removed, are eating a regular diet, and are growing well. In conclusion, the retrosternal ileocolic conduit provides an excellent substitute esophagus in selected pediatric patients, with potential advantages over delayed primary anastomosis or the straight colon or gastric tube interposition because of the antireflux role of the ileocecal valve.

Pathogenesis of systemic air embolism during bronchoscopic Nd:YAG laser operations.

BACKGROUND: The occurrence of systemic air embolism during bronchoscopic neodymium:yttrium-aluminum garnet laser operations has been suspected. Here we describe its mechanism. METHODS: Two patients with embolic cardiac and neurologic complications after bronchoscopic neodymium: yttrium-aluminum garnet laser tumor ablation are described. A subsequent third patient was monitored for intracardiac and aortic air by transesophageal echocardiography. A review of the literature and safety recommendations are discussed. RESULTS: The appearance of systemic air emboli was related to the use of the laser fiber air coolant at high flow and resolved by decreasing the air flow. The presence of intracardiac and aortic air was associated with hypotension and inferior ischemic electrocardiographic changes. CONCLUSIONS: Systemic air embolism during bronchoscopic laser operations is a potentially catastrophic complication and is related to the use of gas-cooled laser fibers and contact probes. We recommend using the noncontact mode whenever possible and maintaining the coaxial coolant air flow at the minimum level or using a fluid coolant if contact is necessary.

Right ventricle-sparing heart transplant: promising new technique for recipients with pulmonary hypertension.

BACKGROUND: Right heart failure remains the leading early cause of mortality after heart transplantation, especially with antecedent pulmonary hypertension. Paradoxically, the discarded recipient right heart, acclimated to pulmonary hypertension, is often stronger than its nonconditioned donor replacement. Heterotopic ("piggyback") transplantation is plagued by problems related to the retained, dilated, hypocontractile left ventricle (lung compression, systemic emboli, arrhythmias). Were it possible to retain the recipient's right heart, excising only the left ventricle, this could have important advantages, especially in severe pulmonary hypertension. This report describes such a technique. METHODS AND RESULTS: In four transplantation experiments (dogs), right ventricular-sparing transplantation proved technically feasible and hemodynamically successful. Bleeding after excision of the left ventricle was easily controlled. Back-bleeding from the native aortic valve (now open into the pericardial space) was not problematic. All atrial, aortic, and pulmonary arterial connections proved feasible. The preserved recipient right heart of all animals remained in stable sinus rhythm. All recipients were easily weaned from cardiopulmonary bypass, maintaining mean arterial pressures 60 to 110 mm Hg. CONCLUSIONS: This investigation develops a technique for donor right ventricle sparing in cardiac transplantation, demonstrating technical and hemodynamic feasibility. This method holds promise for the unsolved clinical problem of right heart failure after orthotopic heart transplantation with antecedent pulmonary hypertension.

Management of descending aortic dissection.

BACKGROUND: Experience with 100 consecutive patients with acute dissection of the descending aorta seen at the Yale Center for Thoracic Aortic Disease over a 10-year period is reported. METHODS: Clinical records from the Yale Center for Thoracic Aortic Disease from 1988 to 1998 were analyzed. This computerized data base included information regarding patients' demographics, history, presenting symptomatology, diagnostic imaging, early hospital course, treatment strategy, and long term follow up (office visits, echocardiography, computerized tomography, magnetic resonance imaging, and home phone calls). RESULTS: The average size of the aorta at the time of dissection was 5.05 cm. Nine patients died (six of complications directly related to the thoracic aorta). Sixty of the 91 surviving patients had a benign course, and 31 had a course complicated by rupture (8), vascular occlusion (17), early expansion or extension (12), and continued pain (4); multiple complications were seen in some patients. Forty-two patients came to operation (22 early and 20 late): 32 direct aortic replacements, 6 fenestration procedures, and 4 thromboexclusions. There were six postoperative deaths and six paraplegias. Clinical experience with the alternative procedures of fenestration and thromboexclusion found both procedures safe and effective for selected categories of patients. Review of the literature indicated that direct aortic replacement in the setting of acute descending aortic dissection continues to carry a very high mortality (28%-65%) and paraplegia rate (30%-35%), leaving room for consideration of alternative procedures. CONCLUSIONS: We recommend a "complication-specific" approach to acute descending aortic dissection: medical management with "antiimpulse therapy" for uncomplicated acute descending dissections and surgical intervention for complicated dissections. Surgical therapy varies for the specific complication: for rupture, direct aortic replacement is recommended; for vascular occlusion, fenestration; and for acute expansion or impending rupture, direct aortic replacement, with thromboexclusion as an option. Chronic descending aortic dissection is treated according to general guidelines for descending aortic aneurysms, with operation for symptoms or enlargement > 6.5 cm.

Should angiographically disease-free saphenous vein grafts be replaced at the time of redo coronary artery bypass grafting?

BACKGROUND: Controversy exists regarding the management of angiographically disease-free saphenous vein grafts at the time of redo coronary artery bypass grafting (CABG). Some authorities favor replacement of these disease-free grafts, arguing that occlusion is likely in the near future. Others believe that these grafts are "biologically privileged" and should not be replaced. METHODS: One hundred thirty-two consecutive patients (113 men, 19 women, aged 46 to 88 years, mean 67 years) underwent redo revascularization with one or more angiographically disease-free saphenous vein grafts at the time of redo CABG. Thirty-six patients had the disease-free grafts replaced (R) and 96 did not (NR). The mean interval from the first CABG was 9.25 years. RESULTS: Surgical mortality was comparable in the NR and R groups (5 of 96 or 5.2% versus 3 of 36 or 8.3%, respectively; p < 0.5). Survival at 1 and 3 years was higher in the NR group than the R group (98% versus 80%, and 95% vs. 66% respectively; p < 0.0001). Late myocardial infarction was less common in the NR group than in the R group (12 of 91 or 12.9% versus 12 of 33 or 36.4%; p < 0.003). Recurrent angina was less common in the NR than in the R group (21 of 91 or 23.1% versus 15 of 33 or 45.5%; p < 0.015). Cardiac hospitalization was required less commonly in the NR than in the R group (11 of 91 or 12.1% versus 12 of 33 or 36.4%; p < 0.002). In nondiseased grafts undergoing angiographic evaluation late after redo CABG, rate of new stenosis was lower in NR grafts than in R grafts (2 of 12 or 16.7% versus 2 of 3 or 66.7%; p < 0.05). CONCLUSIONS: With a conservative approach that does not replace nondiseased saphenous vein grafts at redo CABG (1) there is no increase in operative mortality, (2) good late survival is obtained, (3) clinical ischemia related to the NR saphenous vein grafts is uncommon, and (4) NR grafts continue to be patent. We conclude that disease-free vein grafts may not require routine replacement at redo CABG. A randomized study is required for definitive resolution.

Single-clamp technique does not protect against cerebrovascular accident in coronary artery bypass grafting.

OBJECTIVES: By potentially avoiding the embolic consequences of a side-biting aortic clamp, the single-clamp technique may decrease cerebrovascular accidents in coronary artery bypass grafting. However, this theoretical superiority in stroke prevention has not been conclusively demonstrated and use of this technique may lead to adverse myocardial effects due to longer cross-clamp times. In this study, we sought to determine if the single-clamp technique prevents postoperative stroke in clinical practice. METHODS: Of 607 consecutive isolated coronary bypass operations completed over a 3 year period, 301 (50%) were performed by one surgeon using exclusively the single-clamp technique and 306 (50%) were performed by a second surgeon using exclusively the two-clamp technique. Postoperative adverse events were retrospectively compared between these two groups. RESULTS: There were no differences between groups in terms of postoperative stroke (1.7% single-clamp vs. 2.0% two-clamp, P=0.78), hospital mortality (2.7% single-clamp vs. 1.6% two-clamp, P=0.38), or perioperative myocardial infarction (2.6% single-clamp vs. 0.7% two-clamp, P=0.052). The two-clamp technique was not a significant predictor of stroke by logistic regression analysis (P=0.72). CONCLUSIONS: We conclude that there are no statistically significant differences between clamp techniques with regard to stroke prevention or myocardial protection. We find no compelling evidence for surgeons successfully utilizing one technique to change to the other.