[Hybrid operation theatre from the point of view of cardiac surgery. The future for the heart team]. / Hybridoperationssaal aus Sicht der Herzchirurgie. Zukunft für das Herzteam.

Nowadays, increasing numbers of procedures jointly conducted by cardiac surgeons and cardiologists are performed as minimally invasive surgical procedures or interventions. Transcatheter aortic valve implantation, endovascular aortic aneurysm repair and a large variety of hybrid procedures for congenital heart disease have become current standards. Some of these hybrid procedures were shown to improve the therapeutic safety and efficacy, effects particularly true for high-risk patients and complex interventions. Hybrid procedures require indirect imaging, commonly provided by an angiography system in the hybrid operation theatre. This article describes the technical prerequisites required for a hybrid operation theatre as well as indications and rationales for hybrid procedures conducted in this environment. It is likely that the indications for cardiovascular hybrid procedures will continue to be expanded and that the hybrid operation theatre may become a laboratory for developing innovative approaches in the cardiovascular field. Therefore, the hybrid operation theatre will not only be the working environment for hybrid surgeons and interventionalists but also help to evolve their future.

Procurement regimens to reduce ischemia reperfusion injury of vascular grafts.

BACKGROUND: Ischemia reperfusion injury is an important nonimmunological factor contributing to the development of chronic rejection. The aim of this study was to compare different cell culture media in terms of vascular lesion formation after ischemia reperfusion injury. METHODS: BALB/c aortic grafts were incubated in different cell media (endothelial cell growth, ECG, RPMI-1640 and Waymouth/Ham's F12) for various time spans (5, 6.5 and 8.5 h) at 37°C and implanted into syngeneic BALB/c recipients. On day 30 after implantation, histology, immunofluorescence and morphometric measurements were performed. RESULTS: A total of 36 transplants were performed for this study with an overall survival rate of 72.2%. The most frequent complication was thrombosis of the aortic graft (n = 9) and there was one late death due to other courses. All the recipients with vascular grafts incubated in the ECG medium survived and showed no signs of intimal proliferation independent of the time of ischemia. Aortic grafts incubated in the RPMI medium resulted in a reduced recipient survival rate of 66.7% and grafts incubated in the Waymouth medium showed only a 50% survival by day 30. Analysis of the vascular morphology revealed moderate amounts of intimal proliferation within two aortic grafts in this group. CD31 staining revealed superior endothelial cell integrity after incubation with the ECG medium. CONCLUSIONS: Data from the current study suggest that under optimized conditions vascular grafts can be safely kept in tissue culture up to 8.5 h without significant ischemic damage. Differences in vascular integrity and animal survival depended mostly on the respective tissue culture medium used for the storage of the vessel.

Human cytomegalovirus infection leads to elevated levels of transplant arteriosclerosis in a humanized mouse aortic xenograft model.

Recent findings emphasized an important role of human cytomegalovirus (HCMV) infection in the development of transplant arteriosclerosis. Therefore, the aim of this study was to develop a human peripheral blood lymphocyte (hu-PBL)/Rag-2(-/-) γc(-/-) mouse-xenograft-model to investigate both immunological as well as viral effector mechanisms in the progression of transplant arteriosclerosis. For this, sidebranches from the internal mammary artery were recovered during coronary artery bypass graft surgery, tissue-typed and infected with HCMV. Then, size-matched sidebranches were implanted into the infrarenal aorta of Rag-2(-/-) γc(-/-) mice. The animals were reconstituted with human peripheral blood mononuclear cells (PBMCs) 7 days after transplantation. HCMV-infection was confirmed by Taqman-PCR and immunofluorescence analyses. Arterial grafts were analyzed by histology on day 40 after transplantation. PBMC-reconstituted Rag-2(-/-) γc(-/-) animals showed splenic chimerism levels ranging from 1-16% human cells. After reconstitution, Rag-2(-/-) γc(-/-) mice developed human leukocyte infiltrates in their grafts and vascular lesions that were significantly elevated after infection. Cellular infiltration revealed significantly increased ICAM-1 and PDGF-R-ß expression after HCMV-infection of the graft. Arterial grafts from unreconstituted Rag-2(-/-) γc(-/-) recipients showed no vascular lesions. These data demonstrate a causative relationship between HCMV-infection as an isolated risk factor and the development of transplant-arteriosclerosis in a humanized mouse arterial-transplant-model possibly by elevated ICAM-1 and PDGF-R-ß expression.

Noninvasive magnetic resonance imaging of vessels affected by transplant arteriosclerosis in an experimental mouse aortic allograft model.

BACKGROUND: Transplant arteriosclerosis is still the leading cause of late mortality after heart transplantation despite advances in immunosuppression regimes. Experimental mouse models have substantially contributed to a better understanding of the multifactorial pathogenesis, but the major limitation of these studies is the difficulty in monitoring progression of transplant arteriosclerosis over time. Therefore, the aim of this study was to investigate whether MR measurements are sensitive enough to detect characteristic vascular lesions in a small animal transplantation model. METHODS: For this purpose we investigated 22 iso- and allogeneic aortic graft transplanted mice in vivo with a 4.7 T MR scanner using a 2D-RARE technique, 3D time-of-flight angiography and 3D phase contrast angiography as well as a special snake-based reconstruction algorithm. The MR lumen values of patency from native images and from 3D vessel reconstructions of the respective methods were correlated with conventional histological analysis. RESULTS: A comparison of the different techniques showed that angiographic MR modalities correlated well with histological measurements. 2D-RARE sequences were inferior to the sequences obtained by other ones. Superior correlations and the most accurate results were found for vessel reconstruction based on 3D angiographic time-of-flight data. CONCLUSION: These data demonstrate that mouse in vivo MR imaging is sensitive enough to detect and quantify vascular changes caused by transplant arteriosclerosis.

The use of preoperative intra-aortic balloon pump in open heart surgery.

AIM: Intra-aortic balloon pump (IABP) therapy before open heart surgery has been suggested for ''high risk'' patients. METHODS: Records from patients undergoing open heart surgery at our institution between June 1999 and February 2002 were reviewed. Indication for IABP insertion was severely impaired left ventricular function, acute myocardial infarction (MI) or unstable angina. RESULTS: Fifty-five patients were included in the study: 41 male, 14 female, age 64+/-9 years. Fifty-one (92.7%) required coronary artery bypass brafting (CABG) alone or as a combined procedure, 2 (3.6%) required mitral valve surgery, and 2 (3.6%) needed more complex cardiac procedures. Thirty-two patients (58%) underwent emergency cardiac surgery and 11 patients (20%) suffered from acute preoperative MI. The overall 30 days mortality was 9%. Mean intensive care unit (ICU) stay was 6+/-8 days. Four patients (7.2%) developed postoperative renal failure requiring temporary hemodialysis. Three patients (5.4%) developed IABP related peripheral vascular complications. CONCLUSIONS: Perioperative morbidity and mortality is increased despite preoperative IABP, particularly in patients with acute MI. In contrast to studies not using this approach, preoperative IABP reduces morbidity and mortality of high risk patients. IABP related complications are low. Our data suggest that high risk patients profit from preoperative IABP therapy, however, prospective studies are needed to confirm these findings.

Critical role for IL-4 in the development of transplant arteriosclerosis in the absence of CD40-CD154 costimulation.

Blockade of the CD40-CD154 pathway can inhibit CD4(+) T cell activation but is unable to prevent immune responses mediated by CD8(+) T cells. However, even in the absence of CD8(+) T cells, inhibition of the CD40-CD154 pathway is insufficient to prevent the development of transplant arteriosclerosis. This study investigated the mechanisms of transplant arteriosclerosis in the absence of the CD40 pathway. C57BL/6 CD40(-/-) (H2(b)) recipients were transplanted with MHC-mismatched BALB/c (H2(d)) aortas. Transplant arteriosclerosis was evident in both CD40(-/-) and CD40(+/-) mice (intimal proliferation was 59 +/- 5% for CD40(-/-) mice vs 58 +/- 4% for CD40(+/-) mice) in the presence or absence of CD8(+) T cells (intimal proliferation was 46 +/- 7% for CD40(-/-) anti-CD8-treated mice vs 50 +/- 10% for CD40(+/-) anti-CD8-treated mice), confirming that CD8(+) T cells are not essential effector cells for the development of this disease. In CD40(-/-) recipients depleted of CD8(+) T cells, the number of eosinophils infiltrating the graft was markedly increased (109 +/- 24 eosinophils/grid for CD40(-/-) anti-CD8-treated mice vs 28 +/- 7 for CD40(+/-) anti-CD8-treated mice). The increased presence of eosinophils correlated with augmented intragraft production of IL-4. To test the hypothesis that IL-4 was responsible for the intimal proliferation, CD8 T cell-depleted CD40(-/-) recipients were treated with anti-IL-4 mAb. This resulted in significantly reduced eosinophil infiltration into the graft (12 +/- 5 eosinophils/grid for CD40(-/-) anti-CD8(+), anti-IL-4-treated mice vs 109 +/- 24 for CD40(-/-) anti-CD8-treated mice), intragraft eotaxin, CCR3 mRNA production, and the level of intimal proliferation (18 +/- 5% for CD40(-/-) anti-CD8(+)-, anti-IL-4-treated mice vs 46 +/- 7% for CD40(-/-) anti-CD8-treated mice). In conclusion, elevated intragraft IL-4 production results in an eosinophil infiltrate and is an important mechanism for CD8(+) T cell-independent transplant arteriosclerosis in the absence of CD40-CD154 costimulation.

Development of a combined cardiac and aortic transplant model to investigate the development of transplant arteriosclerosis in the mouse.

BACKGROUND: The degree of transplant arteriosclerosis in murine cardiac allografts is difficult to assess. Aortic allografts represent an alternative model for evaluating the impact of novel transplant strategies on transplant arteriosclerosis in which the vascular changes can be quantified easily. However, it remains controversial as to whether vascular lesions seen in this model are equivalent to those that develop in solid-organ transplants. The aim of this study was to develop a model of combined cardiac and aortic transplantation to allow more precise quantification of transplant arteriosclerosis and to establish a correlation between the lesions that develop in the 2 types of graft. METHODS: CBA (H2(k)) recipients received a C57BL/10 (H2(b)) cervical cardiac allograft on Day 0 and a C57BL/10 (H2(b)) abdominal aortic allograft on Day 1. Recipients were treated with anti-CD154 mAb (MR1) on Days 0, 2, and 4. We performed histology and morphometric measurements for both grafts 30 days after transplantation. RESULTS: We observed significant intimal proliferation in both the cervical cardiac and abdominal aortic allografts from recipients treated with anti-CD154 mAb (heart, 64% +/- 9%; aorta, 67% +/- 8%; n = 5). Abdominal aortic grafts transplanted alone into anti-CD154-treated recipients developed a degree of transplant arteriosclerosis equivalent to that seen in the aortic grafts of the combined group (aorta alone, 68% +/- 9%, vs aorta + heart, 67% +/- 8%; n = 5). CONCLUSIONS: This combined cardiac and aortic transplant model permitted quantitative assessment of transplant arteriosclerosis while monitoring graft survival by cardiac palpation. Furthermore, development of transplant arteriosclerosis was equivalent in abdominal aortic allografts either in the presence or absence of an additional solid- organ transplant.

Intragraft interleukin-4 mRNA expression after short-term CD154 blockade may trigger delayed development of transplant arteriosclerosis in the absence of CD8+ T cells.

BACKGROUND: It has recently been shown that, although anti-CD154 induces CD4+ T-cell tolerance, it is unable to prevent allograft rejection mediated by CD8+ T cells. We have also shown that anti-CD154 monotherapy does not protect the graft from the development of transplant arteriosclerosis even in the absence of CD8+ T cells. This study was designed to investigate and characterize possible mechanisms responsible for the development of transplant arteriosclerosis after CD154 blockade in the absence of CD8+ T cells. METHODS: C57BL/6 (H2b) recipients received a fully MHC-mismatched BALB/c donor aorta (H2d). Animals were either treated with anti-CD154 monoclonal antibody (mAb) in the presence or absence of CD8 T cells. Histology, morphometric measurements, immunohistochemistry, and the production of alloantibodies (IgM, IgG1, IgG2a) were analyzed on days 14, 30, and 50 after transplantation. Cytokine production within the graft was investigated by competitive reverse transcription-polymerase chain reaction on day 14. RESULTS: Combined treatment with anti-CD154 and a depleting CD8 mAb resulted in a delay in the development of transplant arteriosclerosis (intimal proliferation: 33+/-10% vs. 67+/-11% untreated control, day 30) but ultimately did not prevent its progression (intimal proliferation: 55+/-10% vs. 78+/-9% untreated control, day 50). Although there was a significant decrease in the number of CD4+, CD11b+, and CD40+ graft-infiltrating cells and a reduction in the formation of donor-specific IgG1 alloantibodies in recipients treated with anti-CD154 and anti-CD8 mAbs, mRNA for interleukin (IL)-4 was increased, suggesting a shift in the intragraft cytokine profile towards a Th2-like pattern. CONCLUSIONS: Our data provide evidence that short-term CD154 blockade is insufficient to prevent transplant arteriosclerosis, even in combination with CD8+ T-cell depletion. Moreover, the increased expression of the Th2 cytokine interleukin-4 within the graft may be responsible for the development of transplant arteriosclerosis in the long term.

CD8+ T cells contribute to the development of transplant arteriosclerosis despite CD154 blockade.

BACKGROUND: The CD40-CD154 receptor-ligand pair plays a critical role in allograft rejection by mediating the activation of endothelial cells, antigen-presenting cells, and T cells. Blockade of this interaction prevents acute allograft rejection and leads to prolonged allograft survival in numerous experimental models, but in most cases indefinite graft survival is not achieved due to evolving transplant arteriosclerosis. In this study, we have used a model of transplant arteriosclerosis to investigate whether CD4+ and CD8+ T cells are differentially affected by CD154 blockade. METHODS: BALB/c (H2d) aortic grafts were transplanted into C57BL/6 (H2b) recipients treated with anti-CD154 monoclonal antibody in the presence or absence of CD8+ T-cell depletion. Histology and morphometric measurements were performed on day 30 after transplantation. RESULTS: Only combined treatment with anti-CD154 and anti-CD8 monoclonal antibodies resulted in a significant reduction of intimal proliferation (33 +/-10% vs. 67+/-14%; untreated control). Administration of either antibody alone did not produce this effect. Thymectomy did not alter the degree of intimal proliferation observed in any of the treatment groups. CONCLUSIONS: Our data provide direct evidence that CD8+ T cells are not targeted effectively by CD154 blockade and that the transplant arteriosclerosis seen after CD154 blockade is not due to recent thymic emigrant T cells.