Pediatric Living Lung Donor Transplant Candidates: Psychiatric Status of Utilized and Non-Utilized Donors.

Living donor lung (lobar) transplantation has greatly decreased in the past decade due to the success of the lung allocation score (LAS) system, instituted in 2005 by the Organ Procurement and Transplantation Network (OPTN). Between 1993 and 2006, 460 living lung donor transplants were performed in the United States with 369 donations occurring at the University of Southern California and Washington University in St. Louis. These two centers accounted for over 80% of all living donor lung transplants between 1994 and 2006. All potential donors received a psychological/psychiatric evaluation as part of the donor selection process, which is standard practice in the United States, Europe, and Asia. Utilized and non-utilized lung donors were compared in terms of their psychiatric history and present status. Results indicated that 31% (N = 54) of the total sample had a lifetime prevalence of a psychiatric disorder, which is less than that the 46% lifetime rate for the general population (Kessler in Arch Gen Psychiatry 62:593-602, 2005). This study did find that psychiatric history or status was not exclusion factor for transplant surgery in either group. This observation about psychiatric issues in potential living lung donors should be useful to transplant centers who utilize adult live donors of any solid organ type for pediatric recipients and in Japan where live donor lung transplants still represent a significant proportion of lung transplants (Date in J Thorac Dis 8: S631-S636, 2016).

Early onset of deep sternal wound infection after cardiac surgery is associated with decreased survival: A propensity weighted analysis.

OBJECTIVES: To compare outcomes after the development of early (≤30 days) versus delayed (>30 days) deep sternal wound infection (DSWI) after cardiac surgery. METHODS: Between 2005 and 2016, 64 patients were treated surgically for DSWI following cardiac surgery. Thirty-three developed early DSWI, while 31 developed late DSWI. The mean follow-up was 34.1 ± 32.3 months. RESULTS: Survival for the entire cohort at 1, 3, and 5 years was 93.9%, 85.1%, and 80.8%, respectively. DSWI diagnosed early and attempted medical management was strongly associated with overall mortality (hazard ratio [HR], 25.0 and 9.9; 95% confidence intervals [CIs], 1.18-52.8 and 1.28-76.5; p-value .04 and .04, respectively). Survival was 88.1%, 77.0%, 70.6% and 100%, 94.0% and 94.0% at 1, 3, and 5 years in the early and late DSWI groups, respectively (log-rank = 0.074). Those diagnosed early were more likely to have a positive wound culture (odds ratio [OR], 0.06; 95% CI, 0.01-0.69; p = .024) and diagnosed late were more likely to be female (OR, 8.75; 95% CI, 2.0-38.4; p = .004) and require an urgent DSWI procedure (OR, 9.25; 95% CI, 1.86-45.9; p = .007). Both early diagnosis of DSWI and initial attempted medial management were strongly associated with mortality (HR, 7.48; 95% CI, 1.38-40.4; p = .019 and HR, 7.76; 95% CI, 1.67-35.9; p = .009, respectively). CONCLUSIONS: Early aggressive surgical therapy for DSWI after cardiac surgery results in excellent outcomes. Those diagnosed with DSWI early and who have failed initial medical management have increased mortality.

Equivalent outcomes with minimally invasive and sternotomy mitral valve repair for degenerative mitral valve disease.

BACKGROUND: Debate continues in regard to the optimal surgical approach to the mitral valve for degenerative disease. METHODS: Between February 2004 and July 2015, 363 patients underwent mitral valve repair for degenerative mitral valve disease via either sternotomy (sternotomy, n = 109) or small right anterior thoracotomy (minimally invasive, n = 259). Survival, need for mitral valve reoperation, and progression of mitral regurgitation more than two grades were compared between cohorts using time-based statistical methods and inverse probability weighting. RESULTS: Survival at 1, 5, and 10 years were 99.2, 98.3, and 96.8 for the sternotomy group and 98.1, 94.9, and 94.9 for the minimally invasive group (hazard ratio: 0.39, 95% confidence interval [CI] 0.11-1.30, p = .14). The cumulative incidence of need for mitral valve reoperation with death as a competing outcome at 1, 3, and 5 years were 2.7%, 2.7%, and 2.7% in the sternotomy cohort and 1.5%, 3.3%, and 4.1% for the minimally invasive group (subhazard ratio (SHR) 1.17, 95% CI: 0.33-4.20, p = .81). Cumulative incidence of progression of mitral regurgitation more than two grades with death as a competing outcome at 1, 3, and 5 years were 5.5%, 14.4%, and 44.5% for the sternotomy cohort and 4.2%, 9.7%, and 20.5% for the minimally invasive cohort (SHR: 0.67, 95% CI: 0.28-1.63, p = .38). Inverse probability weighted time-based analyses based on preoperative cohort assignment also demonstrated equivalent outcomes between surgical approaches. CONCLUSIONS: Minimally invasive and sternotomy mitral valve repair in patients with degenerative mitral valve disease is associated with equivalent survival and repair durability.

Use of a Bluetooth tablet-based technology to improve outcomes in lung transplantation: A pilot study.

The impact of remote patient monitoring platforms to support the postoperative care of solid organ transplant recipients is evolving. In an observational pilot study, 28 lung transplant recipients were enrolled in a novel postdischarge home monitoring program and compared to 28 matched controls during a 2-year period. Primary endpoints included hospital readmissions and total days readmitted. Secondary endpoints were survival and inflation-adjusted hospital readmission charges. In univariate analyses, monitoring was associated with reduced readmissions (incidence rate ratio [IRR]: 0.56; 95% confidence interval [CI]: 0.41-0.76; P < .001), days readmitted (IRR: 0.46; 95% CI: 0.42-0.51; P < .001), and hospital charges (IRR: 0.52; 95% CI: 0.51-0.54; P < .001). Multivariate analyses also showed that remote monitoring was associated with lower incidence of readmission (IRR: 0.38; 95% CI: 0.23-0.63; P < .001), days readmitted (IRR: 0.14; 95% CI: 0.05-0.37; P < .001), and readmission charges (IRR: 0.11; 95% CI: 0.03-0.46; P = .002). There were 2 deaths among monitored patients compared to 6 for controls; however, this difference was not significant. This pilot study in lung transplant recipients suggests that supplementing postdischarge care with remote monitoring may be useful in preventing readmissions, reducing subsequent inpatient days, and controlling hospital charges. A multicenter, randomized control trial should be conducted to validate these findings.

Double-gated myocardial ASL perfusion imaging is robust to heart rate variation.

PURPOSE: Cardiac motion is a dominant source of physiological noise (PN) in myocardial arterial spin labeled (ASL) perfusion imaging. This study investigates the sensitivity to heart rate variation (HRV) of double-gated myocardial ASL compared with the more widely used single-gated method. METHODS: Double-gating and single-gating were performed on 10 healthy volunteers (n = 10, 3F/7M; age, 23-34 years) and eight heart transplant recipients (n = 8, 1F/7M; age, 26-76 years) at rest in the randomized order. Myocardial blood flow (MBF), PN, temporal signal-to-noise ratio (SNR), and HRV were measured. RESULTS: HRV ranged from 0.2 to 7.8 bpm. Double-gating PN did not depend on HRV, while single-gating PN increased with HRV. Over all subjects, double-gating provided a significant reduction in global PN (from 0.20 ± 0.15 to 0.11 ± 0.03 mL/g/min; P = 0.01) and per-segment PN (from 0.33 ± 0.23 to 0.21 ± 0.12 mL/g/min; P < 0.001), with significant increases in global temporal SNR (from 11 ± 8 to 18 ± 8; P = 0.02) and per-segment temporal SNR (from 7 ± 4 to 11 ± 12; P < 0.001) without significant difference in measured MBF. CONCLUSION: Single-gated myocardial ASL suffers from reduced temporal SNR, while double-gated myocardial ASL provides consistent temporal SNR independent of HRV. Magn Reson Med 77:1975-1980, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Assessment of segmental myocardial blood flow and myocardial perfusion reserve by adenosine-stress myocardial arterial spin labeling perfusion imaging.

PURPOSE: To determine the feasibility of measuring increases in myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) on a per-segment basis using arterial spin labeled (ASL) magnetic resonance imaging (MRI) with adenosine vasodilator stress in normal human myocardium. MATERIALS AND METHODS: Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine 3T MR adenosine-induced vasodilator stress protocol and were performed in 10 healthy human volunteers. Myocardial ASL was performed using single-gated flow-sensitive alternating inversion recovery (FAIR) tagging and balanced steady-state free precession (bSSFP) imaging at 3T. A T2 -prep blood oxygen level-dependent (BOLD) SSFP sequence was used to concurrently assess segmental myocardial oxygenation with BOLD signal intensity (SI) percent change in the same subjects. RESULTS: There was a statistically significant difference between MBF measured by ASL at rest (1.75 ± 0.86 ml/g/min) compared to adenosine stress (4.58 ± 2.14 ml/g/min) for all wall segments (P < 0.0001), yielding a per-segment MPR of 3.02 ± 1.51. When wall segments were divided into specific segmental myocardial perfusion territories (ie, anteroseptal, anterior, anterolateral, inferolateral, inferior, and inferoseptal), the differences between rest and stress regional MBF for each territory remained consistently statistically significant (P < 0.001) after correcting for multiple comparisons. CONCLUSION: This study demonstrates the feasibility of measuring MBF and MPR on a segmental basis by single-gated cardiac ASL in normal volunteers. Second, this study demonstrates the feasibility of performing the ASL sequence and T2 -prepared SSFP BOLD imaging during a single adenosine infusion. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:413-420.

CT-guided tube pericardiostomy: a safe and effective technique in the management of postsurgical pericardial effusion.

OBJECTIVE: The purpose of this study was to analyze the efficacy and examine the competitive cost of CT-guided tube pericardiostomy in the management of symptomatic postsurgical pericardial effusion. MATERIALS AND METHODS: Over a 4-year period, 36 patients with symptomatic pericardial effusion were treated with CT-guided percutaneous placement of an indwelling pericardial catheter, for a total of 39 CT-guided tube pericardiostomy procedures. Thirty-three patients (92%) had undergone major cardiothoracic surgery, and three patients (8%) had undergone minimally invasive procedures. The medical records were retrospectively reviewed for clinical presentation, surgical history, imaging studies performed, procedural details, fluid characterization, and outcome. Charge comparison was performed with the American Medical Association Current Procedural Terminology codes and information acquired from the billing department at our facility. RESULTS: All 39 CT-guided tube pericardiostomy procedures were performed successfully without clinically significant complications. After 33 of the 39 procedures (85%), symptoms did not recur after the catheter was removed. Three of 36 patients (8%) had a recurrence of pericardial effusion. Comparison of procedure charges showed an 89% saving over intraoperative pericardial window procedures and no significant difference compared with ultrasound-guided tube pericardiostomy. Eight patients (21% of procedures) needed pleural drainage procedures, all of which were performed in the CT suite immediately after the tube pericardiostomy procedure. CONCLUSION: CT-guided tube pericardiostomy is a safe and effective alternative to surgical drainage in the care of patients with clinically significant pericardial effusion after cardiothoracic surgery and has the additional benefit of substantial cost savings.

Extracorporeal photopheresis: past, present, and future.

Extracorporeal photopheresis (ECP) is a leukapheresis-based therapy that uses 8-methoxypsoralen and ultraviolet A irradiation. Used alone or in combination with biological agents, ECP is an established and effective therapy for advanced cutaneous T-cell lymphoma. ECP has also shown promising efficacy in a number of other severe and difficult-to-treat conditions, including systemic sclerosis, graft-versus-host disease, prevention and treatment of rejection in solid organ transplantation, and Crohn disease. Furthermore, the use of ECP in some of these conditions may allow a significant reduction in the use of systemic steroids and other immunosuppressants, reducing long-term morbidity and mortality. The accumulated experience shows ECP to be well tolerated, with no clinically significant side effects. Progress is also being made in the search for understanding of the mechanisms of action of ECP, which will ultimately facilitate improvements in the use of this therapy.

Outcomes after lung retransplantation in the modern era.

RATIONALE: Characteristics of and survival estimates for recipients of lung retransplantation in the modern era are unknown. OBJECTIVES: To compare lung retransplant patients in the modern era with historical retransplant patients, to compare retransplant patients with initial transplant patients in the modern era, and to determine the predictors of the risk of death after lung retransplantation. METHODS: We performed a retrospective cohort study of patients who underwent lung retransplantation between January 2001 and May 2006 in the United States (modern retransplant cohort). The characteristics and survival of this cohort were compared with those of patients who underwent first lung retransplantation between January 1990 and December 2000 (historical retransplant cohort) and patients who underwent initial lung transplantation between January 2001 and May 2006 (modern initial transplant cohort). MEASUREMENTS AND MAIN RESULTS: Modern retransplant recipients (n = 205) had a lower risk of death compared with that of the historical retransplant cohort (n = 184) (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = 0.006). However, modern retransplant recipients had a higher risk of death than that of patients who underwent initial lung transplantation (n = 5,657) (hazard ratio, 1.3; 95% confidence interval, 1.2-1.5; P = 0.001), which appeared to be explained by a higher prevalence of certain comorbidities. Retransplantation at less than 30 days after the initial transplant procedure was associated with worse survival. CONCLUSIONS: Outcomes after lung retransplantation have improved; however, retransplantation continues to pose an increased risk of death compared with the initial transplant procedure. Retransplantation early after the initial transplant poses a particularly high mortality risk.

Genetic modulation of CD44 expression by intragraft fibroblasts.

This study investigated the genetic composition and the functional implication of CD44 species expressed by intragraft fibroblasts. An LEW-to-F344 heart transplant model of chronic rejection was used. Intragraft fibroblasts recovered from the chronically rejecting allografts displayed a 4.5-fold increase in expression of CD44 mRNA when compared with that of the fibroblasts isolated from non-rejecting heart allografts (P < 0.01). The intragraft fibroblasts preferentially expressed CD44 variant isoforms containing v1 exon transcript. Automated nucleotide sequence analysis revealed that the majority (90.12%) of the CD44 v1 isoforms expressed by the rejecting graft fibroblasts were encoded by a mutated CD44 mRNA, which contained two point mutations and a codon deletion in the v1 coding region. Histochemistry demonstrated a massive deposition of extracellular HA in the rejecting heart allografts. Hyaluronic acid (HA) was able to promote in vitro fibroblast adhesion, migration in a CD44-dependent manner, and survival in a serum-free culture condition. The study concludes that up-regulation of CD44 v1 isoforms expressed by the intragraft fibroblasts is associated with an increase in the deposition of extracellular HA, the principal ligand for CD44, in the allografts, suggesting that CD44-HA interaction plays an important role in regulating fibroblast recruitment and growth in allografts developing chronic rejection.

Selective Aortic Arch and Root Replacement in Repair of Acute Type A Aortic Dissection.

BACKGROUND: Controversy exists regarding the optimal extent of repair for type A aortic dissection. Our approach is to replace the ascending aorta, and only replace the aortic root or arch when intimal tears are present in those areas. We examined intermediate outcomes with this approach to acute type A aortic dissection repair. METHODS: Between March 2005 and October 2016, 195 patients underwent repair of acute type A aortic dissection. Repair was categorized by site of proximal and distal anastomosis and extent of repair. Mean follow-up was 31.0 ± 30.9 months. Kaplan-Meier analysis was used to assess survival. Multiple variable Cox proportional hazards modeling was utilized to identify factors associated with overall mortality. RESULTS: Overall survival was 85.1%, 83.9%, 79.1%, and 74.4% at 6, 12, 36, and 60 months, respectively. Eight patients required reintervention. The cumulative incidence of aortic reintervention at 1 year with death as a competing outcome was 3.95%. Multiple variable regression analysis identified factors such as age, preoperative renal failure, concomitant thoracic endograft, postoperative myocardial infarction and sepsis, and need for extracorporeal membrane oxygenation as predictive of overall mortality. Neither proximal or distal extent of repair, nor need for reintervention affected overall survival (proximal: hazard ratio 1.63, 95% confidence interval: 0.75 to 3.51, p = 0.22; distal: hazard ratio 1.12, 95% confidence interval: 0.43 to 2.97, p = 0.81; reintervention: hazard ratio 0.03, 95% confidence interval: 0.002 to 0.490, p < 0.01). CONCLUSIONS: A selective approach to root and arch repair in acute type A aortic dissection is safe. If aortic reintervention is needed, survival does not appear to be affected.

Hemodynamics influences vascular peroxynitrite formation: Implication for low-density lipoprotein apo-B-100 nitration.

Hemodynamics, specifically, fluid shear stress, modulates the focal nature of atherogenesis. Superoxide anion (O2(-.)) reacts with nitric oxide (.NO) at a rapid diffusion-limited rate to form peroxynitrite (O2(-.) + .NO-->ONOO(-)). Immunohistostaining of human coronary arterial bifurcations or curvatures, where OSS develops, revealed the presence of nitrotyrosine staining, a fingerprint of peroxynitrite; whereas in straight segments, where PSS occurs, nitrotyrosine was absent. We examined vascular nitrative stress in models of oscillatory (OSS) and pulsatile shear stress (PSS). Bovine aortic endothelial cells (BAEC) were exposed to fluid shear stress that simulates arterial blood flow: (1) PSS at a mean shear stress (tau(ave)) of 23 dyn cm(-2) and a temporal gradient (partial differential(tau)/partial differential(t)) at 71 dyn cm(-2) s(-1), and (2) OSS at tau(ave) = 0.02 dyn cm(- 2) and partial differential(tau)/partial differential(t) = +/- 3.0 dyn cm(-2) s(-1) at a frequency of 1 Hz. OSS significantly up-regulated one of the NADPH oxidase subunits (NOx4) expression accompanied with an increase in O2(-.) production. In contrast, PSS up-regulated eNOS expression accompanied with .NO production (total NO(2)(-) and NO(3)(-)). To demonstrate that O2(-.) and .NO are implicated in ONOO(-) formation, we added low-density lipoprotein cholesterol (LDL) to the medium in which BAEC were exposed to the above flow conditions. The medium was analyzed for LDL apo-B-100 nitrotyrosine by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS). OSS induced higher levels of 3-nitrotyrosine, dityrosine, and o-hydroxyphenylalanine compared with PSS. In the presence of ONOO(-), specific apo-B-100 tyrosine residues underwent nitration in the alpha and beta helices: alpha-1 (Tyr(144)), alpha-2 (Tyr(2524)), beta-2 (Tyr(3295)), alpha-3 (Tyr(4116)), and beta-2 (Tyr(4211)). Hence, the characteristics of shear stress in the arterial bifurcations influenced the relative production of O2(-.) and .NO with an implication for ONOO(-) formation as evidenced by LDL protein nitration.

The Utility of Nurse-Managed Extracorporeal Life Support in an Adult Cardiac Intensive Care Unit.

BACKGROUND: The use of extracorporeal life support (ECLS) worldwide has increased exponentially since 2009. The patient requiring ECLS demands an investment of hospital resources, including personnel. Educating bedside nurses to manage ECLS circuits broadens the availability of trained providers. METHODS: Experienced cardiothoracic intensive care unit (CTICU) nurses underwent training to manage ECLS circuits, including volume assessment, treatment of arterial blood gas values, the physiology of ECLS, and recognition of common emergencies. In addition to lectures and a written examination, simulation using water circuits and an ICU model allowed assessment of skills and understanding of concepts. Performance assessments were completed regularly at the bedside, and skills revalidation occurred every 6 months. A sequential cohort of 40 patients was tracked over 1 year. RESULTS: Despite doubling the census of ECLS patients in 1 year, management by specially trained CTICU nurses has positively affected patient care and outcomes. At a single institution, 40 patients had a median of 6 days (interquartile range, 2 to 226 days) of support in 2014, leading to 767 patient-days of support. Survival to hospital discharge increased to 45% in 2014. Most survivors were weaned from support. Neurologic injury was the most common cause of death, followed by failure to qualify for advanced therapies. CONCLUSIONS: With on-going education and assessment, including crisis training, physiology, and cannulation strategies, CTICU nurses can safely operate ECLS circuits and can increase the availability of appropriately trained providers to accommodate the exponential increase in ECLS occurrences without negatively affecting outcomes and generally at a lower cost.

Outcomes after mitral valve repair: A single-center 16-year experience.

OBJECTIVE: To evaluate outcomes after mitral valve repair. METHODS: Between May 1999 and June 2015, 446 patients underwent mitral valve repair. Isolated mitral valve annuloplasty was excluded. A total of 398 (89%) had degenerative valve disease. Mean follow-up was 5.5 ± 3.8 years. Postoperative echocardiograms were obtained in 334 patients (75%) at a mean of 24.3 ± 13.7 months. RESULTS: Survival was 97%, 96%, 95%, and 94% at 1, 3, 5, and 10 years. Risk factor analysis showed age >60 years and nondegenerative etiology predict death (hazard ratio, 2.91; 95% confidence interval, 1.06-8.02, P = .038; and hazard ratio, 1.87; 95% confidence interval, 1.16-3.02, P = .010, respectively). Considering competing risks due to mortality, the cumulative incidence of reoperation was 2.8%, 4.2%, 5.1%, and 9.6% at 1, 3, 5, and 10 years. Competing risk proportional hazard survival regression identified nondegenerative etiology and previous cardiac surgery as predictors of reoperation, and posterior repair was protective (all P < .05). Cumulative incidence of progression of mitral regurgitation (2 or more grades) with mortality as a competing risk was 4.7%, 10.5%, 21.0%, and 35.8% at 1, 3, 5, and 10 years. Patients with previous sternotomy, repair or coronary artery bypass grafting, and concurrent tricuspid valve procedure or isolated anterior leaflet repair were more likely to develop progression of mitral regurgitation (all P < .05), and posterior leaflet repair was protective (P = .038). On multivariate analysis diabetes, previous coronary artery bypass grafting and concurrent tricuspid valve intervention predicted MR progression. CONCLUSIONS: Mitral valve repair has excellent outcomes. Our results demonstrate failures appear to occur less in those who undergo posterior leaflet repair.

A comparison of aortic valve replacement via an anterior right minithoracotomy with standard sternotomy: a propensity score analysis of 492 patients.

OBJECTIVES: Right anterior minithoracotomy with central arterial cannulation is our preferred technique of minimally invasive aortic valve replacement (AVR). We compared perioperative outcomes with this technique to those via sternotomy. METHODS: Between March 1999 and December 2013, 492 patients underwent isolated AVR via either sternotomy (SAVR, n = 198) or minimally invasive right anterior thoracotomy (MIAVR, n = 294) in our institution. Univariate comparisons between groups were made to evaluate overall outcomes and adverse events. To control treatment selection bias, propensity scores were constructed from core patient characteristics. A propensity score-stratified analysis of outcome and adverse events was then performed. RESULTS: Overall mortality was 2.5 and 1.0% in the SAVR and MIAVR groups, respectively. Hospital and ICU stays were shorter, there was less intraoperative blood product usage, and fewer wound infections in the MIAVR group. There were no differences in other adverse events, including strokes. The composite end-point of alive and adverse event-free was significantly more common in the MIAVR group (83 vs 74%, P = 0.002). After adjusting for the propensity score, hospital and ICU stays remained shorter and intraoperative blood product usage remained less in the MIAVR group. There was no difference in mortality, stroke or other adverse events between groups. CONCLUSION: Minimally invasive AVR via an anterior right thoracotomy with predominately central cannulation can be performed with morbidity and mortality similar to that of a sternotomy approach. There appear to be advantages to this minimally invasive approach when compared with sternotomy in terms of less intraoperative blood product usage, lower wound infection rates and decreased hospital stays. If mortality and the occurrence of adverse events are taken together, MIAVR may be associated with better outcomes. As minimally invasive AVR becomes more common, further long-term follow-up is needed and a prospective multicentre randomized trial would be warranted.

The ethics of living donor lung transplantation.

A constant awareness of the risk to the living donors must be maintained with any living donor organ transplantation program, and comprehensive short- and long-term follow-up should be strongly encouraged to maintain the viability of these potentially life-saving procedures. There has been no perioperative or long-term mortality following lobectomy for living lobar lung transplantation, and perioperative risks associated with donor lobectomy seem to be similar to those seen with standard lung resections. These risks might increase, however, if the procedure is offered on an occasional basis and not within a well-established program. The long-term outcomes and functional effects of lobar donation raise important questions that are unanswered. This has proved difficult to follow closely, because of the fact that many donors live far from the transplant medical center and are reluctant to return for routine follow-up evaluation. The death of a recipient can further exacerbate this situation, because there is reluctance to insist on further routine examinations for a grieving donor. Prospective donors must be informed of the morbidity associated with lobectomy and the potential for mortality, and for potential negative recipient outcomes in regard to life expectancy and quality of life after transplantation. Although cadaveric transplantation must be considered because of the risk to the donors, living lobar lung transplantation should continue to be used under properly selected circumstances. The results reported by the authors' group and others are important if this procedure is to be considered as an option at more pulmonary transplant centers in view of the institutional, regional, and international differences in the philosophic and ethical acceptance of the use of living organ donors for transplantation. The integration of ethical discussion into topics that are relevant and of interest to thoracic surgeons, such as living lung donation, is a recent and welcome event. Many of the clinical situations that thoracic surgeons deal with on a daily basis have important and complex ethical implications, and there has been little training to deal effectively with these issues. This is changing as invited discussions on ethically compelling topics are finding their way into journals and the programs of national meetings. What may be of more importance, however, is the development of an ethics curriculum for those training in the specialty. The core curriculum recommended by the Thoracic Surgical Directors Association (which represents the leadership of the 89 approved residency training programs in the United States) has one lecture pertaining to ethics out of the several hundred offerings in its requisite curriculum. It is hoped that this will change in the near future.

Migration of mesenchymal stem cells to heart allografts during chronic rejection.

BACKGROUND: Mesenchymal stem cells (MSC) are pluripotent progenitors for a variety of cell types, including fibroblasts and muscle cells. Their involvement in the tissue repair of allografts during the development of chronic rejection has been hypothesized, but not yet substantiated, by experimental evidence. METHODS: Rat MSC were isolated from circulation using an aortic pouch allograft as a trapping device. The plasticity of these cells was examined in differentiation cultures. One of the resulting MSC lines was immortalized and transduced to express a marker gene. The -labeled cells were then transferred to F344 rats bearing Lewis (LEW) cardiac allografts to measure their localization and contribution to graft tissue repair. RESULTS: The MSC isolated from circulation exhibited multipotential for differentiation in culture, developing into various lineages including osteoblasts, lipocytes, chondrocytes, myotubes, and fibroblasts. Intravenous engraftment of the -labeled cells into recipients of heart transplant resulted in migration of the beta-gal+ cells into the lesions of chronic rejection in the cardiac grafts and homing of the cells to the bone marrow. The majority of beta-gal+ cells present in the allografts exhibited fibroblast phenotypes, and a small number of the cells expressed desmin, indicative of myocyte differentiation. CONCLUSION: MSC vigorously migrated into the site of allograft rejection. This data suggests that they may be attracted to this site to actively participate in tissue repair during chronic rejection. In addition, given the robust migration, the inhibition of MSC differentiation toward fibroblast progeny and induction toward the myocyte lineage may serve as a new strategy for treatment of chronic rejection and allograft tissue repair.

Evidence for recipient derived fibroblast recruitment and activation during the development of chronic cardiac allograft rejection.

BACKGROUND: Allograft fibrosis is a prominent feature of chronic rejection. Although intragraft fibroblasts contribute to this process, their origin and exact role remain poorly understood. METHODS: 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. RESULTS: 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; P<0.05 and <0.05, 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. CONCLUSION: 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.

Depopulated vena caval homograft: a new venous conduit.

OBJECTIVE: Completion of the Fontan procedure is frequently performed by using an extracardiac conduit between the inferior vena cava and the pulmonary artery. Most centers use a polytetrafluoroethylene graft for the extracardiac conduit, and because re-endothelialization is unlikely, anticoagulation is used for a variable period. This study explores the use of an alternate large-caliber venous conduit. METHODS: The superior vena cava was replaced in 8 minipigs with either a polytetrafluoroethylene interposition graft (2 pigs) or a depopulated (acellular), cryopreserved superior vena caval homograft (6 pigs). After 6 months, the animals were killed, and the grafts were examined for patency and histology, including immunostaining. No anticoagulation was used. RESULTS: Polytetrafluoroethylene grafts have a cross-sectional luminal narrowing, ranging from 16% to 40%. Histology showed only partial intimal ingrowth, with excessive subendothelial fibrosis and early calcification. In contrast, the depopulated venous homografts showed minimal luminal narrowing, ranging from 2% to 9%. These grafts were completely repopulated by the recipient with an endothelial lining, which stained positively for factor VIII, and a subendothelial region appropriately recellularized by myofibroblasts, which stained positively for smooth muscle actin and procollagen. There was no evidence of an immune response to the venous homografts, as judged by staining for T-cell surface antigen, CD4, and CD8. Thrombus was not seen in any of the grafts. CONCLUSION: Depopulated, cryopreserved vena caval homografts might be superior conduits for cavopulmonary connection during completion of the Fontan operation by using the extracardiac conduit technique.