Single ventricle palliation of truncus arteriosus with mitral atresia, interrupted aortic arch, and aberrant right subclavian artery.

The association of truncus arteriosus communis with interrupted aortic arch and mitral atresia is an exceptionally rare congenital defect. We describe the initial decision-making and management of this lesion, which eventually achieved a Fontan palliation.

Neointimal Hyperplasia after Carotid Transection and Anastomosis Surgery is Associated with Degradation of Decorin and Platelet Derived Growth Factor Signaling.

OBJECTIVE: Intimal hyperplasia (IH) is the expansion of the vascular intimal region after intervention, which can lead to stenosis and eventual failure of vascular grafts or interventional procedures such as angioplasty or stent placement. Our goals were to investigate the development of IH in a rabbit open surgical model and to evaluate the associated pathophysiological processes involving decorin and the platelet derived growth factor-BB / platelet derived growth factor receptor-ß / mitogen activated protein kinase (PDGF/PDGFR-ß/MAPK) pathway. METHODS: We conducted carotid transection and primary anastomosis on five New Zealand White rabbits to induce IH and examined the associated pathophysiological changes. Tissue was obtained for histological and protein analysis on post-operative day 21 using the contralateral vessel as a control. Intimal medial thickness (IMT) was calculated to measure IH and compared with the unoperated side. Western blot analysis was performed on tissue lysates to determine the expression of decorin core protein, PDGF-BB, PDGFR-ß, and phosphorylated-MAPK (ph-MAPK). Immunofluorescence microscopy was used to assess tissue distribution of matrix metalloproteinase-2 (MMP-2) and phosphorylated-PDGFR-ß (ph-PDGFR-ß). RESULTS: Bilateral carotid arteries were harvested on postoperative day 21. We compared the IMT in operated with unoperated specimens. IMT was significantly elevated in operated arteries vs. unoperated arteries in all 5 animals (148.6 µm +/- 9.09 vs. 103.40 µm +/- 7.08; 135.2 µm +/- 8.30 vs. 92.40 µm +/- 2.35; 203.1 µm +/- 30.23 vs.104.00 µm +/- 4.52; 236.2 µm +/- 27.22 vs. 141.50 µm +/- 9.95; 226.9 µm +/- 11.12 vs. 98.8 µm +/- 3.78). Western blot analysis revealed degradation of decorin protein in the operated tissue, including loss of a 50 kDa band and the appearance of a cleaved fragment at 10 kDa. Decorin and MMP-2 were observed, via immunofluorescence microscopy, in the neointima of the operated vessels. Western blot analysis also revealed increased PDGF-BB, PDGFR-ß, and ph-MAPK levels in operated tissue. Immunofluorescent staining for ph-PDGFR-ß primarily localized to the neointima, indicating increased signaling through PDGF in this region. CONCLUSION: Carotid transection and primary reanastomosis in rabbits induced IH that was associated with MMP-2 activation, degradation of decorin, and activation of the PDGF/PDGFR-ß /MAPK pathway. The findings in this study should lead to further mechanistic evaluation of these pathways to better understand the potential to modify the intimal hyperplastic response to surgery.

Correlating Oxygen Delivery During Cardiopulmonary Bypass With the Neurologic Injury Biomarker Ubiquitin C-Terminal Hydrolase L1 (UCH-L1).

OBJECTIVE: The authors sought to assess the relationship between low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) and a neuron-specific biomarker of neurologic injury, ubiquitin C-terminal hydrolase L1 (UCH-L1). DESIGN: Retrospective analysis of patient charts and prospectively collected blood samples. SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: Adult patients undergoing cardiac surgery on CPB. INTERVENTIONS: Serum UCH-L1 levels were drawn at baseline and 6 and 24 hours after CPB cessation. DO2 was computed from perfusion records, with area-under-the-curve (AUC) computations performed to account for distance of DO2 excursions below predefined DO2 thresholds and the amount of time spent below them. Strokes were defined radiographically using computed tomography and magnetic resonance imaging. MEASUREMENTS AND MAIN RESULTS: Forty-three adults were included (median age 65 y, interquartile range 59-72). Three patients experienced strokes (imaged at 2, 7, and 8 d postoperatively). Most patients underwent isolated coronary artery bypass grafting (41%, 18 patients) or isolated aortic valve replacement (30%, 13). Median UCH-L1 levels differed from baseline to 6 and 24 hours after CPB (40, 232, and 166 pg/mL, respectively; p < 0.001). On multivariable linear regression analysis controlling for baseline and surgical variables, only DO2 AUC <225 was significantly associated with 6-hour UCH-L1 levels (p = 0.001), whereas only DO2 AUC <300 was significantly associated with 24- hour levels (p < 0.001). The 3 patients who experienced radiographic strokes had nonsignificantly elevated 24-hour UCH-L1 levels compared with control patients (585 v 151 pg/mL, p = 0.11). CONCLUSIONS: This is the first study to demonstrate an independent association between DO2 during CPB and elevations of a brain injury biomarker; additional study is needed to clarify the clinical significance of these results.

Brain injury in canine models of cardiac surgery.

Neuropathology and neurologic impairment were characterized in a clinically relevant canine model of hypothermic (18°C) circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1 hour of HCA (n = 20), or standard CPB (n = 22) and survived 2, 8, 24, or 72 hours. Neurologic impairment and neuropathology were much more severe after 2-hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit scores were significantly correlated. Apoptosis developed as early as 2 hours after injury and was most severe in the granule cells of the hippocampal dentate gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal neurons in the cornu ammonis hippocampus. Neuronal injury was minimal up to 24 hours after 1-hour HCA, but 1 dog that survived to 72 hours showed substantial necrosis in the hippocampus, suggesting that, with longer survival time, the injury was worse. Although neuronal injury was minimal after CPB, we observed rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These results have important implications for CPB in humans and may help explain the subtle cognitive changes experienced by patients after CPB.

Increased exposure improves recruitment: early results of a program designed to attract medical students into surgical careers.

BACKGROUND: In recent years, general surgery and surgical subspecialty residency interests have remained somewhat static among medical students, casting some doubt on recruitment of the best students. A summer research program was designed to introduce interested medical students to surgical careers. METHODS: In 2003, the division of cardiac surgery instituted an 8-week structured summer research experience for second-year medical students. Three students were competitively chosen from a pool of 20 to 30 interested applicants every year. They were taught basic operative suturing and knot-tying techniques. Students participated in large animal research projects, witnessed clinical operations, and developed individual clinical projects with an attending cardiac surgeon. The summer experience culminated with oral presentations to the cardiac surgery division, with many students producing manuscripts for publication or presentation at national meetings. RESULTS: From 2003 to 2012, 30 students participated in the program. Of 23 participants who had applied for residency, 12 (52.2%) matched into general surgery or a surgical subspecialty, including 3 into plastic surgery, 2 into cardiothoracic surgery, 1 into orthopedic surgery, and 1 into neurosurgery. These students produced 64 publications and presented at 51 national and regional meetings. CONCLUSIONS: These results suggest that an 8-week, structured program introducing students to cardiothoracic surgery can successfully attract students into surgical careers. The percentage (52%) of these students entering a surgical career compares favorably with national residency match results (16%) and graduating Johns Hopkins medical students (22%). Increased effort for early exposure to surgery may be a key factor in generating and securing surgical interest among medical students.

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

Prognostic value of the pre-transplant diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension.

BACKGROUND: Although the transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) are commonly used to differentiate heart failure patients with pulmonary vascular disease from those with passive pulmonary hypertension (PH), elevations in TPG and PVR may not always reflect pre-capillary PH. Recently, it has been suggested an elevated diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient (DPG) may be a better indicator of pulmonary vascular remodeling, and therefore, may be of added prognostic value in patients with PH being considered for cardiac transplantation. METHODS: Using the United Network for Organ Sharing (UNOS) database, we retrospectively reviewed all primary adult (age > 17 years) orthotropic heart transplant recipients between 1998 and 2011. All patients with available pre-transplant hemodynamic data and PH (mean pulmonary artery pressure ≥ 25 mm Hg) were included (n = 16,811). We assessed the prognostic value of DPG on post-transplant survival in patients with PH and an elevated TPG and PVR. RESULTS: In patients with PH and a TPG > 12 mm Hg (n = 5,827), there was no difference in survival at up to 5 years post-transplant between high DPG (defined as ≥3, ≥5, ≥7, or ≥10 mm Hg) and low DPG (<3, <5, <7, or <10 mm Hg) groups. Similarly, there was no difference in survival between high and low DPG groups in those with a PVR > 3 Wood units (n = 6,270). Defining an elevated TPG as > 15 mm Hg (n = 3,065) or an elevated PVR > 5 (n = 1,783) yielded similar results. CONCLUSIONS: This large analysis investigating the prognostic value of DPG found an elevated DPG had no effect on post-transplant survival in patients with PH and an elevated TPG and PVR.

Disclosure of physician-specific behavior improves blood utilization protocol adherence in cardiac surgery.

BACKGROUND: Evidence indicates that a transfusion (Tx) trigger hemoglobin (Hgb) value of 8 gm/dL may be safer than a more liberal Tx trigger in cardiac surgery (CS) patients. We hypothesized that weekly physician feedback would improve adherence to such a protocol, but that the public identification of individual physician behavior would have an additive effect. METHODS: We concurrently reviewed all adult CS patients at our institution from December 1, 2010 to May 27, 2011. We matched any cardiac surgery intensive care unit Tx event (red blood cells) with the Hgb value immediately before Tx. Patients requiring massive transfusions (>10 units/24 hours) were excluded. After all providers agreed upon a Hgb of 8 as the Tx trigger, we studied 3 consecutive time periods: no feedback, weekly feedback of group Tx behavior, and weekly feedback with identification of individual surgeon Tx behavior. RESULTS: Of the 512 patients who underwent cardiac operations, 144 patients underwent 510 Tx events. Compared with period 1, the unadjusted odds of receiving a Tx above 8 gm/dL decreased by 48% in study period 2(odds ratio: 0.52, p < 0.01), and 63% in study period 3(odds ratio: 0.37, p <0.001). Single unit transfusion rates increased from 77% to greater than 90% (p < 0.001). In-hospital mortality also fell from period 1 to period 3 (7.0% to 1.5%, p = 0.02) with the observed to expected mortality ratio decreasing from 2.19 to 0.51. CONCLUSIONS: Blood transfusion protocol adherence improves when weekly feedback is provided. Identifying individual surgeon behavior improves adherence to a greater degree. Routine presentation of quality metrics with identification of individual physician-specific behavior may be the most effective way to accomplish performance improvement.

Functional status is highly predictive of outcomes after redo lung transplantation: an analysis of 390 cases in the modern era.

BACKGROUND: The aim of this study was to evaluate whether functional status is a predictor of outcomes after redo lung transplantation (LTx). METHODS: Adults undergoing redo LTx after implementation of the Lung Allocation Score (May 2005 to December 2010) were identified in the United Network for Organ Sharing database. Patients were stratified into three groups based on functional status as measured before redo LTx by the Karnofsky scale: (1) no assistance required, (2) some assistance required, and (3) total assistance required. Outcomes after redo LTx were compared based on these preoperative functional cohorts. RESULTS: A total of 390 redo LTx were identified: 44 (11%) required no functional assistance, 176 (45%) required some assistance, and 170 (44%) required total assistance preoperatively. Overall survival at 1 year after redo LTx was significantly reduced in the total assistance group (56% versus 82% no assistance, versus 82% some assistance; p < 0.001). After risk adjustment, recipients requiring total assistance preoperatively were at significant risk for 1-year mortality (odds ratio 3.72, p = 0.02). Overall, the preoperative functional assessment outperformed the Lung Allocation Score in predicting 1-year survival after redo LTx (c-index: 0.68 versus 0.58). Transplant survivors who required total assistance before redo LTx were also at increased risk of requiring total assistance after redo LTx (26% versus 0% no assistance, versus 3% some assistance; p < 0.001). CONCLUSIONS: These data suggest that performing redo LTx in patients requiring total functional assistance is associated with significant risk of early mortality and continued functional limitation, findings that may have important implications in organ allocation.

Septuagenarians bridged to heart transplantation with a ventricular assist device have outcomes similar to younger patients.

BACKGROUND: Although orthotopic heart transplantation (OHT) is increasingly being offered to older patients, few studies have evaluated outcomes in patients older than 70 years of age. We undertook this study to characterize the outcomes of septuagenarians bridged to transplantation (BTT) in the modern era. METHODS: We conducted a retrospective cohort study of all adult OHT in the United Network for Organ Sharing database from 2005 to 2011. Primary stratification was by age 70 years or older. Subgroup analysis evaluated patients who received BTT. The primary outcome was survival as determined by the Kaplan-Meier method. RESULTS: From January 2005 to December 2011, 12,274 adults underwent OHT, including 3,243 (26.4%) who received BTT. In the entire cohort, 11,996 (97.7%) recipients were aged 18 to 70 years, and 277 (2.3%) were 70 years of age or older. Overall, patients 70 years or older who underwent OHT had decreased 90-day survival (93.6% versus 88.8%; p<0.01), 1-year survival (89.0% versus 81.6%; p<0.01), and 2-year survival (85.4% versus 79.9%; p<0.01) compared with recipients of other ages. However in the BTT subgroup, recipients 70 years and older (n=43) had similar 90-day (91.2% versus 84.7%; p=0.2), 1-year (86.1% versus 81.7%; p=0.4), and 2-year (82.8% versus 81.7%; p=0.6) survival compared with recipients of other ages (n=3,200). After adjusting for multiple recipient and donor factors, age greater than or equal to 70 years was still not associated with an increased hazard of mortality at 90 days, 1 year, or 2 years. These results were verified by analysis of a propensity-matched cohort. CONCLUSIONS: Although patients older than the age of 70 years undergoing OHT have decreased survival, among patients who received BTT, septuagenarians have outcomes similar to those of younger recipients. In carefully selected patients dependent on left ventricular assist devices (LVADs), recipient age greater than or equal to 70 years should not be viewed as a contraindication to OHT.

Unilateral humoral rejection after reoperative single-lung transplant.

The role of antibody-mediated rejection in acute and chronic rejection after lung transplantation is poorly understood. We report the case of a prior single-lung transplant recipient undergoing an acute antibody-mediated rejection isolated to her new, contralateral single-lung transplant. A 44-year-old woman 6 years after undergoing a single-lung transplant for idiopathic pulmonary fibrosis underwent a second single-lung transplant for bronchiolitis obliterans syndrome. Despite a negative crossmatch, she subsequently exhibited severe antibody-mediated rejection to her new allograft within 6 days of transplantation. The process of allograft sensitization is dynamic, and further study is warranted to better understand this process.

A physiologic and biochemical profile of clinically rejected lungs on a normothermic ex vivo lung perfusion platform.

BACKGROUND: Although ex vivo lung perfusion (EVLP) is increasingly being used to evaluate and manipulate potential donor lungs before lung transplantation (LTx), data on the biochemistry of lungs during EVLP are limited. In this study, we examined the physiology and biochemistry of human lungs on an EVLP circuit. METHODS: We recovered unallocated double lungs in standard fashion and split them into single lungs. All lungs received a nebulized arginase inhibitor, 2-S-amino-6-boronohexanoic acid (ABH), at either the onset (n = 6) or after 3 h (n = 8) of EVLP. Serial biochemical analysis included levels of arginase, endogenous nitric oxide synthase (eNOS), cyclic guanosine monophosphate, and reactive oxygen species. We considered lungs transplantable if they sustained a PaO2:FiO2 ≥ 350 in addition to stable pulmonary function during EVLP. RESULTS: We recovered a total of 14 single lungs. We deemed three single lungs from different donors to be transplantable after EVLP. These lungs had superior oxygenation, lower carbon dioxide, and more stable pulmonary artery pressures. Transplantable lungs had higher baseline levels of eNOS and higher final levels of cyclic guanosine monophosphate than non-transplantable lungs. Early ABH administration was associated with a transient increase in dynamic compliance. CONCLUSIONS: In this biochemical characterization of lungs deemed unsuitable for LTx, early levels of eNOS and late levels of cyclic guanosine monophosphate appear to be associated with improved allograft function during EVLP. In addition, nebulized ABH is associated with a significant increase in dynamic compliance. These data suggest that biochemical markers during EVLP may predict acceptable allograft function, and that this platform can be used to biochemically manipulate donor lungs before LTx.

The role of head computed tomography imaging in the evaluation of postoperative neurologic deficits in cardiac surgery patients.

BACKGROUND: Computed tomography (CT) scans of the head without contrast are routinely obtained to evaluate neurologic deficits after cardiac surgery, but their utility is unknown. We evaluated our experience with this imaging modality to determine its value. METHODS: We retrospectively identified cardiac surgery patients with postoperative neurologic deficits occurring during the first week after surgery between January 2000 and December 2012. Stroke was defined by neurologist's determination, whereas a nonfocal deficit (NFD) was defined by the presence of seizure, delirium, or cognitive impairment. We defined early noncontrast head CT as occurring within 7 days of surgery. Outcomes included positive findings on CT, in-hospital mortality, and length of stay. Multivariate logistic regression identified predictors of positive findings on head CT. RESULTS: Within the population of 11,070 postoperative patients, 451 had early noncontrast head CT scans (4%). Two hundred two (44.7%) were associated with stroke, and 249 (55.2%) were associated with NFD. Among stroke patients, 40 of 202 (20%) showed acute infarction, 17 of 202 (8%) showed subacute infarction, and 5 of 202 (2%) showed hemorrhage. Among NFD patients, 1 of 248 (0.4%) showed acute infarction, 4 of 248 (1.6%) showed subacute infarction, and 1 of 248 (0.4%) showed hemorrhage. There was no difference in in-hospital mortality (stroke, 42 of 201 [21%] versus NFD, 41 of 248 [16%]; p = 0.2) or length of stay (stroke, 24 d versus NFD, 22 d; p = 0.5). On multivariable logistic regression, only focal deficits and aortic procedures predicted a positive finding on CT scan. CONCLUSIONS: This study reviewed the utility of early postoperative noncontrast head CT in cardiac surgery patients. With focal neurologic deficits, this imaging modality was positive for approximately one third of patients, but rarely positive for NFD. Its use in this setting has limited utility.

Pre-transplant malignancy: an analysis of outcomes after thoracic organ transplantation.

BACKGROUND: Pre-transplant malignancy (PTM) is a relative contraindication to organ transplantation. Studies examining the effect of PTM on outcomes after lung transplantation (LTx) or orthotopic heart transplantation (OHT) are limited. We evaluated the effect of PTM on outcomes after LTx and OHT. METHODS: We retrospectively reviewed primary adult LTx and OHT recipients in the United Network for Organ Sharing database. Primary stratification was by PTM and secondary stratification by tumor type. Matched cohorts (2:1) and multivariable Cox proportional hazards regression models were used to evaluate mortality. RESULTS: From 2000 to 2011, 13,613 adults underwent LTx and 19,817 underwent OHT. PTM was present in 740 LTx patients (5.4%) and in 1,117 OHT patients (5.6%). On unadjusted analysis, LTx patients and OHT patients with PTM had similar 30-day, 1-year, and 5-year survivals (p<0.05) compared with patients with no PTM. These findings persisted after risk-adjustment . No tumor types were associated with increased mortality in LTx patients. OHT patients with leukemia, lymphoma, or myeloma (LLM) had a significant increase in univariate mortality at 30 days (hazard ratio [HR], 1.82; p = 0.04), 1 year (HR, 1.93; p<0.001), and 5 years (HR, 1.54; p = 0.01). Matched cohort analysis revealed comparable outcomes in LTx patients but confirmed increased univariate 1-year mortality (HR, 1.89; p = 0.006) in OHT patients with LLM. CONCLUSIONS: This large study evaluating the effects of PTM found the incidence of PTM was in LTx 5.4% and in OHT 5.6%. In general, PTM does not increase mortality in either cohort; however, OHT patients with LLM have an increased hazard of mortality. Therefore, carefully selected patients with PTM should not be excluded from LTx or OHT.

Respiratory support with venovenous extracorporeal membrane oxygenation during stenting of tracheobronchomalacia.

A subset of patients with severe airway disease cannot be adequately supported with conventional mechanical ventilation during complex airway procedures. We report the successful respiratory support of a patient with severe tracheobronchomalacia with venovenous extracorporeal membrane oxygenation during rigid bronchoscopy with stent removal and stent placement.

The effect of center volume on the incidence of postoperative complications and their impact on survival after lung transplantation.

OBJECTIVE: The aim of this study was to evaluate the effect of center volume on the incidence of postoperative complications and their impact on survival after lung transplantation (LTx). METHODS: United Network for Organ Sharing data were used to identify adult patients undergoing LTx between 1999 and 2009. Center volume was modeled as both a continuous and a categorical variable. Postoperative complications included infection, rejection, stroke, reoperation, and renal failure requiring dialysis. Multivariable Cox regression and Kaplan-Meier analyses were conducted after stratification on the basis of center volume and type of complication. RESULTS: A total of 12,565 LTx recipients were included in the study. Overall rates of postoperative complications were 5.4% for renal failure requiring dialysis, 1.9% for stroke, 19.9% for reoperation, 42.8% for infection, and 10.0% for rejection. High volume centers did not have significantly reduced rates of postoperative complications. Risk-adjusted multivariable Cox analysis demonstrated that in patients with a complication, low volume center was a significant risk factor for increased 90-day, 1-year, and 5-year mortality. Kaplan-Meier analyses similarly demonstrated reduced posttransplant survival in lower volume centers, a finding that persisted after stratification based on individual complication type except for stroke. CONCLUSIONS: Although high volume centers do not have significantly lower incidences of individual postoperative complications after LTx, they are best able to minimize the adverse effects of these complications on short- and long-term survival. These data suggest that identifying and implementing the institutional practices that lead to better management of postoperative complications after LTx in high volume centers may be prudent to improving outcomes in lower volume hospitals.

Reoperative sternotomy is associated with increased mortality after heart transplantation.

BACKGROUND: Although several studies have examined factors affecting survival after orthotopic heart transplantation (OHT), few have evaluated the impact of reoperative sternotomy. We undertook this study to examine the incidence and impact of repeat sternotomies on OHT outcomes. METHODS: We conducted a retrospective review of all adult OHT from 2 institutions. Primary stratification was by the number of prior sternotomies. The primary outcome was survival. Secondary outcomes included blood product utilization and commonly encountered postoperative complications. Multivariable Cox proportional hazards regression models examined mortality while linear regression models examined blood utilization. RESULTS: From January 1995 to October 2011, 631 OHT were performed. Of these, 25 (4.0%) were redo OHT and 182 (28.8%) were bridged to transplant with a ventricular assist device; 356 (56.4%) had undergone at least 1 prior sternotomy. On unadjusted analysis, reoperative sternotomy was associated with decreased 90-day (98.5% vs 90.2%, p<0.001), 1-year (93.1% vs 79.6%, p<0.001), and 5-year (80.4% vs 70.1%, p=0.002) survival. This difference persisted on multivariable analysis at 90 days (hazard ratio [HR] 2.99, p=0.01), 1 year (HR 2.98, p=0.002), and 5 years (HR 1.62, p=0.049). The impact of an increasing number of prior sternotomies was negligible. On multivariable analysis, an increasing number of prior sternotomies was associated with increased intraoperative blood product utilization. Increasing blood utilization was associated with decreased 90-day, 1-year, and 5-year survival. CONCLUSIONS: Reoperative sternotomy is associated with increased mortality and blood utilization after OHT. Patients with more than 1 prior sternotomy do not experience additional increased mortality. Carefully selected patients with multiple prior sternotomies have decreased but acceptable outcomes.

Outcomes and temporal trends among high-risk patients after lung transplantation in the United States.

INTRODUCTION: Although several studies have evaluated risk factors for death after lung transplantation (LTx), few studies have focused on the highest-risk recipients. We undertook this study to evaluate the effect of high lung allocation scores (LAS), ventilator support, and extracorporeal membrane oxygenation (ECMO) support on outcomes after LTx. METHODS: We retrospectively reviewed all LTx recipients in the United Network for Organ Sharing database. Primary stratification was by recipient acuity at the time of LTx. The 3 strata consisted of (1) recipients in the highest LAS quartile (LAS ≥ 48.4), (2) those requiring ventilator support, and (3) those requiring ECMO support. The primary outcome was 1-year mortality. Sub-group analysis focused on temporal trends. RESULTS: From May 2005 to June 2011, 9,267 adults underwent LTx. Before LTx, 1,874 (20.2%) were in the highest LAS quartile, 526 (5.7%) required ventilator support, and 122 (1.3%) required ECMO support. Unadjusted analysis showed decreased 1-year survival associated with ventilator (67.7%) and ECMO support (57.6%) compared with the highest LAS quartile (81.0%; p < 0.001 for each comparison). These differences persisted on adjusted analysis for ventilator support (hazard ratio, 1.99, p < 0.001) and ECMO support (hazard ratio, 3.03; p < 0.001). Increasing annual center volume was associated with decreased mortality. In patients bridged to LTx with ECMO support, 1-year survival improved over time (coefficient, 8.03% per year; p = 0.06). CONCLUSIONS: High-acuity LTx recipients, particularly those bridged with ventilator or ECMO support, have increased short-term mortality after LTx. However, since the introduction of the LAS, high-risk patients have demonstrated improving outcomes, particularly at high-volume centers.

Inhaled hydrogen sulfide improves graft function in an experimental model of lung transplantation.

OBJECTIVES: Ischemia/reperfusion injury (IRI) is a common complication of lung transplantation (LTx). Hydrogen sulfide (H(2)S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pretreatment with inhaled H(2)S would improve graft function in an ex vivo model of LTx. METHODS: Rabbits (n = 10) were ventilated for 2 h prior to heart-lung bloc procurement. The treatment group (n = 5) inhaled room air (21% O(2)) supplemented with 150 ppm H(2)S while the control group (n = 5) inhaled room air alone. Both groups were gradually cooled to 34°C. All heart-lung blocs were then recovered and cold-stored in low-potassium dextran solution for 18 h. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. RESULTS: Prior to heart-lung bloc procurement, rabbits pretreated with H(2)S exhibited similar oxygenation (P = 0.1), ventilation (P = 0.7), and heart rate (P = 0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures (P = 0.01). During reperfusion, lungs pretreated with H(2)S had better oxygenation (P < 0.01) and ventilation (P = 0.02), as well as lower pulmonary artery pressures (P < 0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion (P = 0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity (P = 0.01). CONCLUSIONS: To our knowledge, this study represents the first reported therapeutic use of inhaled H(2)S in an experimental model of LTx. After prolonged ischemia, lungs pretreated with inhaled H(2)S exhibited improved graft function during reperfusion. Donor pretreatment with inhaled H(2)S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration.