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Background Applications to cardiothoracic training programs have declined dramatically. Increased effort in recruiting trainees is paramount. In this study, we test our hypothesis that mentored instruction on cardiothoracic simulators will enhance the interest of junior medical students in cardiothoracic surgery. Methods First- and second-year medical students were recruited from a "surgery interest group" to receive mentored instruction on high-fidelity cardiothoracic simulators. Before and after simulation assessment tools were used to assess attitudes toward simulation, general surgery, and cardiothoracic surgery. Results Forty-four medical students participated in the study. Although 80% of the students were interested in pursuing a career in surgery before the course, the majority (64%) indicated they were "neutral" about pursuing a career in cardiothoracic surgery. After participating in the course, 61% of the students agreed or strongly agreed that they were interested in pursuing a career in cardiothoracic surgery ( p = 0.001). When asked to select a surgical subspecialty for their third-year clerkship rotation, 18% of the students selected thoracic surgery before participating in the simulator course versus 39% after completing the course. This increase was most evident among the female participants, of whom only 3 (12%) selected a thoracic rotation before the simulator course versus 9 (35%) after completion of the course ( p Conclusions High-fidelity surgical simulators are an effective way to introduce medical students to cardiothoracic surgery. Participation in moderated simulator sessions improves attitudes toward cardiothoracic surgery as a career choice and correlates with a greater interest in selecting thoracic surgery as a third-year clerkship rotation. The role of surgical simulation as a recruitment tool should be further delineated.

Purpose The reversibility of acute renal dysfunction with mechanical circulatory support (MCS) remains controversial. We sought to examine outcomes at our center in MCS patients who required perioperative renal replacement therapy (RRT). Methods and Materials Between 8/10-11/12, 75 patients underwent MCS implant at our institution. 29 required perioperative RRT (RRT). 42 patients did not require RRT (No RRT). 4 chronic RRT patients are excluded. Preoperative characteristics are shown in Table 1. Results More RRT patients were INTERMACS Class 1 and received biventricular MCS (p=0.005 and 0.001 respectively). Survival was significantly different with 30, 180, and 360 day survival of 95, 77, and 77% and 55, 28, and 21% in No RRT vs. RRT (p Conclusions The need for perioperative RRT is associated with high mortality. Consistent with INTERMACS, our study suggests that caution should be exercised when considering MCS in these patients. Preoperative Risk FactorsOverallNo RRTRRTpN7142 (59%)29 (41%)Age (years)61.0±13.159.6±14.063.0±11.70.28Male Sex57 (80.0%)29 (69.0%)25 (86.0%)0.096Preop Creatine (mg/dl)1.46±0.871.30±0.551.69±1.200.0714Preop Creatine Clearance (ml/min)67.8±36.773.7±38.759.3±32.30.1042INTERMACS 133 (46%)12 (29%)21 (72%)0.005INTERMACS 217 (24%)12 (29%)5 (17%)INTERMACS 3-521 (30%)18 (43%)3 (10%)

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long-term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for >/=14 d for persistent air leaks and/or drainage. Right-sided donors were more likely to have a perioperative complication than left-sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live

Living-donor lobar lung transplantation was developed as an alternative to cadaveric transplantation. However, whether two pulmonary lobes provide comparable intermediate and long-term pulmonary function to full-sized bilateral cadaveric grafts in adults is unknown.An analysis of the pulmonary functions of 59 bilateral lobar and 43 bilateral cadaveric adult lung transplant recipients who survived more than 3 months after transplantation was performed.Mean follow-up was 3.8 +/- 2.8 years. In lobar recipients, mean percent predicted forced vital capacity and forced expiratory volume in 1 second improved between 1 and 6 months after transplantation (42.5% +/- 13.4% and 46.9% +/- 14.0% at 1 month versus 63.6% +/- 14.1% and 64.5% +/- 13.7% at 6 months; p0.001 and0.001, respectively). In cadaveric recipients, mean percent predicted forced vital capacity improved after transplantation (54.3% +/- 14.5% at 1 month versus 74.2% +/- 21.3% at 12 months; p0.01). As compared with the cadaveric group, mean percent predicted forced vital capacity and forced expiratory volume in 1 second were lower 1 and 3 months after transplantation in the lobar recipients (p = 0.001 at both times); however, by 6 months after transplantation, these values were comparable and remained so throughout the follow-up period. In a subset of lobar and cadaveric recipients, maximal exercise, heart rate, peak oxygen consumption, anaerobic oxygen consumption threshold, and ability to maintain oxygen saturation were also comparable.In those adult recipients surviving more than 3 months after transplantation, lobar lung transplantation provides comparable intermediate and long-term pulmonary function and exercise capacity to bilateral cadaveric lung transplantation.

Obliterative bronchiolitis (OB) is the histologic correlate of chronic allograft dysfunction in pulmonary transplantation. The histologic diagnosis of OB is challenging, therefore a physiologic definition, bronchiolitis obliterans syndrome (BOS) based on pulmonary function tests has been used as a surrogate marker for OB for the last decade. BOS has proven to be the best available surrogate marker for OB and is predictive of the ultimate endpoints of graft and patient survival. Multiple other clinical markers have been reported and proposed as alternates for or complements to BOS grade, but all need further evaluation and validation in large, prospective clinical trials. Lastly, given the early occurrence and high incidence of chronic allograft dysfunction, the easily measurable endpoint of BOS grade, and our lack of understanding of ways to prevent or alter the course of BOS, lung transplant recipients represent an ideal population for clinical trials targeting prevention and treatment of chronic allograft dysfunction.

CXCR3 chemokines are of particular interest because of their potential involvement in a variety of inflammatory diseases, including the rejection of organ transplants. Although the rat is one of the most appropriate animals for using to study transplantation biology, the structural and functional characteristics of CXCL9 [monokine induced by interferon-gamma (Mig)] in this experimental model have not been described. Therefore, we recently conducted a series of experiments to identify and characterize the rat CXCL9 gene. Accordingly, we isolated rat CXCL9 cDNA and genomic DNA. The rat CXCL9 gene encodes a protein of 125 amino acids and spans a 3.5 kbp DNA segment containing four exons in the protein-coding region. We then analysed mRNA expression in various tissues. Transcripts for the gene were found to be expressed at high levels in the lymph nodes and spleen. Then, to confirm the function of the identified gene, rat CXCL9 was transiently expressed in COS-1 cells. Rat recombinant Mig displayed chemotactic properties and induced CXCR3 internalization in CD4+ T cells. Lastly, we analysed the expression of rat CXCL9 in a heterotopic heart allograft model. Both mRNA and protein levels of intragraft CXCL9 were significantly increased following transplantation of ACI to LEW hearts when compared with syngeneic controls. These findings indicate that rat CXCL9 has an in vivo role in the infiltration of CD4+ T cells in the transplanted graft.

Allograft fibrosis is a prominent feature of chronic rejection. Although intragraft fibroblasts contribute to this process, their origin and exact role remain poorly understood.Using a rat model of chronic rejection, LEW to F344, cardiac fibroblasts were isolated at the point of rejection and examined in a collagen gel contraction assay to measure fibroblast activation. The allograft microenvironment was examined using immunohistochemistry for fibrogenic markers (transforming growth factor [TGF]-beta, platelet-derived growth factor [PDGF], tissue plasminogen activator [TPA], plasminogen activator inhibitor [PAI]-1, matrix metalloproteinase [MMP]-2, and tissue inhibitor of matrix metalloproteinase [TIMP]-2). The origin of intragraft fibroblasts was studied using female to male allografts followed by polymerase chain reaction [PCR] and in situ hybridization for the male sry gene.The cardiac fibroblasts isolated from allografts with chronic rejection exhibited higher gel contractibility (50.9% +/- 6.1% and 68.2% +/- 3.8% at 4 and 24 hr) compared with naive cardiac fibroblasts (30.7% +/- 3.5% and 55.3% +/- 6.6% at 4 and 24 hr; P0.05 and0.05, respectively). Immunostaining for TGF-beta, PDGF, TPA, PAI-1, MMP-2 and TIMP-2 was observed in all allografts at the time of rejection. In situ hybridization demonstrated the presence of sry positive cells in female allografts rejected by male recipients. Sixty-five percent of fibroblast colonies (55 of 85) isolated from female heart allografts expressed the male sry gene.Cardiac fibroblasts are activated and exist in a profibrogenic microenvironment in allografts undergoing chronic rejection. A substantial proportion of intragraft fibroblasts are recruited from allograft recipients in this experimental model of chronic cardiac allograft rejection.

Aortic mural thrombi (AMT) in the absence of aortic disease are rare. The appropriate indications and the efficacy of surgical thrombectomy, thrombolysis, and systemic anticoagulation remain controversial.This study, set in an academic medical center, was a retrospective review of five patients with AMT in the absence of aortic disease who underwent treatment between 1997 and 2001. The main outcome measures were morbidity, mortality, and treatment outcome.Three patients were women, and ages ranged from 40 to 77 years. On admission, all patients had symptoms related to thrombus embolization (extremity pain or abdominal pain). Two patients had a history of venous thromboembolism (pulmonary embolism or deep venous thrombosis). Four patients had biochemical evidence of hypercoaguability, and the fifth had malignant disease. Coagulation disorders included increased homocysteine (n = 2) and factor VIII (n = 1), antithrombin III (n = 1) and protein C deficiency (n = 1), and familial dysfibrinogenemia (n = 1). AMT were located in the infrarenal (n = 1), suprarenal (n = 3), and descending thoracic (n = 1) aorta. One patient needed exploratory laparotomy and one needed lower extremity vascular procedures for visceral and limb-threatening ischemia, respectively. Treatment with systemic anticoagulation therapy resulted in complete resolution on follow-up computed tomographic scan or angiogram of the AMT at a median of 60 days.Most patients in whom AMT develops in the absence of underlying aortic disease have underlying coagulation disorders. Anticoagulation therapy alone allows resolution of AMT, with surgical intervention reserved for management of end organ ischemia from thrombus embolization.

S 28 EACTS 017 AORTIC VALVE REPLACEMENT THROUGH AN ANTERIOR RIGHT MINI-THORACOTOMY WITH CENTRAL AORTIC CANNULATION IS SAFE D. Hui, M. Bowdish, J. Cleveland, R. Ranjan, R. Sinha, C.J. Baker, M.J. Cunningham, V.A. Starnes Department of Cardiothoracic Surgery, University of Southern California, Los Angeles, United States of America Objectives: Sternotomy is the standard approach to aortic valve replacement. We have adopted an approach of minimally invasive aortic valve replacement (AVR) via a right anterior mini-thoracotomy with central arterial cannulation (MIAVR). We compared perioperative outcomes with this technique to those via sternotomy (SAVR). Methods: A prospective observational study of 492 patients who underwent isolated AVR (294 MIAVR, 198 SAVR) between March 1999 and December 2013. Univariate comparisons between groups were made using t-tests or MannWhitney U (non-normally distributed), and c tests (Fisher’s exact or Pearson) for categorical outcomes; a = 0.05 Results: The groups did not differ in age, BMI, creatinine, sex, diabetes, COPD, atrial fibrillation, history of myocardial infarction, or stroke. MIAVR patients were more likely to have a bicuspid valve (35% vs 18%, P = 0.03). In MIAVR patients, central aortic cannulation was utilized in 92% (n = 273). Venous cannulation was central in 86% (n = 255). Conversion to sternotomy was required in 6 patients (2%). Aortic cross-clamp and cardiopulmonary bypass times were similar. MIAVR patients had shorter ICU (2.8 vs 3.2 days, P < 0.01) and hospital stays (8.2 vs 9.7 days, P < 0.01), shorter time to extubation, reduced transfusions, and fewer wound infections (6.6% vs 1%, P < 0.001). Perioperative stroke (1.7% vs 2.5%) and mortality rates (1% vs 2.5%) were similar [see Table 1]. Table 1: Operative characteristics and postoperative outcomes SAVR (N = 198) MIAVR (N = 294) P-value Continued Table 1: (Continued) SAVR (N = 198) MIAVR (N = 294) P-value Valve size (mm) 23.8 ± 2.4 23.4 ± 1.9 0.13 CPB time (min) 81 ± 32 79 ± 33 0.34 Aortic cross-clamp time (min) 59 ± 26 58 ± 25 0.80 Time to extubation (min) 1074 ± 1730 800 ± 2090

A conduit was made by sewing a bovine pericardial valve into a graft conduit with the pseudo-sinuses of Valsalva. The graft collar below the valve cuff ring was sewn to the aortic annulus with interrupted pledgeted sutures. From August 2005 to February 2008, 68 patients underwent aortic root replacements with this technique. Operative mortality was 2.9% (2 acute aortic dissection patients died). During median follow-up of 11 months, 1 patient had reoperation for conduit failure due to infectious endocarditis. This technique is safe and feasible with favorable early outcomes. Because the valve is sewn above the outflow tract, superior hemodynamics are achieved. Reoperation may be accomplished by removal of the valve rather than full root re-replacement.

and TCR-tg mice (n 6) do not acutely reject bm12 hearts (graft survival 33-100 days). However, TCR-tg mice primed with bm12 skin grafts acutely reject bm12 heart grafts (MST 22 days, n 6). Interestingly, TCR-tg recipients of bm12 heart grafts fail to develop chronic rejection compared with B6 recipients. We developed a model to visualize dynamics of CD4 T cell mediated direct allograft rejection and to investigate mechanisms underlying development of transplant tolerance. B6 nude mice were adoptively transferred with 15x10 TCR-tg spleen cells and transplanted with bm12 skin grafts. Expansion of allospecific TCR-tg CD4 T cells was observed primarily in the draining lymph nodes at early time points. Alloantigen-driven TCR-tg CD4 T cell expansion increased 7 fold over homeostatic expansion, peaked 14 days after transplantation, and declined thereafter. TCR-tg CD4 T cells exhibited upregulation of early activation markers, expression of effector/memory markers, and IFNproduction mirroring the kinetics of clonal expansion. We investigated the role of B7-CD28 and B7h-ICOS costimulatory blockade in MHC class II alloreactive CD4 T cell responses using CTLA4Ig and anti-B7h mAb. CTLA4Ig treated recipients exhibited a drastic reduction in TCR-tg CD4 T cell expansion. TCR-tg CD4 T cells also retained a naive phenotype. In contrast, anti-B7h mAb had no effect on expansion or activation of TCR-tg CD4 T cells. CTLA4Ig reduced IFNproduction by 80%, anti-B7h mAb by 20%. Our results represent the first model of MHC class II alloreactive CD4 T cell activation in vivo. It provides a powerful tool for tracking CD4 T cell mediated alloimmune responses and investigating mechanisms of tolerance induction in vivo.

significant univariately were entered into a multiple logistic regression model and retained if significant at the 10% level. Model calibration and discrimination were assessed using the Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve respectively. Results: 757 transplants were studied, 99 of whom died within 30 days. Four risk factors were retained: diagnosis -suppurative (baseline), pulmonary hypertension (Odds Ratio 2.5 (95% CI 1.2 to 5.5)), fibrosis (1.1 (0.4 to 2.8)), COPD (1.5 (0.5 to 2.3)), other (2.5 (1 to 6.2)); ventilation prior to transplantation (3.2 (0.9 to 11.5)); creatinine clearance 80 mls/min (1.7 (1.0 to 2.9)); recipient diabetes (2.0 (0.9 to 4.4)), and ischaemia time (1.5 (1.1 to 2.2)) per increase in time category from 3 hours to 3-4 hours to 4 hours. Calibration using the Hosmer-Lemeshow 2 1.39 (p 0.5) and the area under the ROC curve was 0.71. Conclusion: The risk model developed is well calibrated and produces accurate risk estimates. At present the model only has a moderate ability to discriminate between patients who die from those who survive. This model will continue to be refined as more data are accrued.

Hypothesis Contemporary reconstructive vascular techniques can be safely used to permit resection of tumors invading major vascular structures. Design Review of vascular surgery registry between January 1, 1987, and December 31, 2001. Setting An academic medical center and affiliated institutions. Patients Forty-nine patients (37 males and 12 females) aged 15 through 80 years (mean age, 55 years) who required concomitant vascular resection and reconstruction to allow complete tumor resection. Main Outcome Measures Early ( 30 days) vascular morbidity and mortality, primary patency of the vascular reconstruction, and tumor-free survival. Results Aortic resection with graft reconstruction was performed in 20 patients (41.7%) and inferior vena cava resection with reconstruction in 6 patients (12.5%). Five patients (10.4%) had both the aorta and inferior vena cava resected and reconstructed. Iliac, femoral, or popliteal reconstructions were performed in 15 patients (31.3%). Portal vein reconstruction was performed to permit resection of pancreatic neoplasms in 8 patients (16.7%). Resection and reconstruction of either a brachiocephalic vessel or superior vena cava was performed in 4 patients. Thirty-day mortality was 2.1%, as 1 patient died of a myocardial infarction following tumor resection with vascular reconstruction. Overall 30-day morbidity was 12.2%. Early vascular morbidity included bleeding from an arterial anastomosis and a compartment syndrome requiring fasciotomy. Primary patency of the vascular reconstructions at 24 months was 90% and tumor-free survival was 70%. Thirty-one patients (63%) were alive, without tumor recurrence and with a patent vascular reconstruction at 24 months. No patient died or lost a limb due to occlusion of the vascular reconstruction. Conclusion Contemporary reconstructive vascular procedures permit resection of tumors that involve major vascular structures with acceptable early and late morbidity and mortality.

Objective Living lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation. Methods One hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 ± 7.7 years), and 39 were pediatric patients (age, 13.9 ± 2.9 years). Results The primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients ( P = .65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P = .03; Kaplan-Meier P = .002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50). Conclusion These results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations.

Objective Recent advance in surgical technique facilitates more aggressive approaches for thoracic aortic diseases. We sought to address the outcomes of our strategy of open distal anastomosis with aortic root replacement using axillary cannulation and moderate hypothermia. Methods A retrospective review of 228 patients who underwent aortic root replacement between July 2004 and December 2007 was performed. Results Axillary artery cannulation was successful in 98% of the attempted cases and resulted in no adverse events in 97%. The axillary artery was the site of arterial cannulation in 89% of the cases, among which 136 patients (60% of the cases) underwent an open distal anastomosis, consisting of the cohort of interest. Median age of the patients was 60 years (ranging from 16 to 89 years) with 79% being male. The principal diagnosis for the operation included aneurysmal disease without aortic dissection (78%), type A aortic dissection with or without aneurysm (12%), and endocarditis (5.9%). Performed operations were modified Bentall operation (53% of the cohort), valve-sparing aortic root replacement (26%), and replacement with a homograft (20%). Hemiarch replacement was added in 43%. Mean ± standard deviation of the lowest temperature was 27°C ±2.6°C. There were 5 deaths (mortality 3.7%). A total of 16 patients (12%) had major complications. Conclusions Open distal anastomosis at the time of aortic root replacement can safely be performed with axillary artery cannulation and moderate hypothermia. Axillary cannulation provides a reliable route of antegrade cerebral perfusion and enables the complex procedure to be performed without deep hypothermic circulatory arrest.