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To establish expert consensus regarding the domains and topics for senior surgery residents (PGY-4) to make critical decisions and assume senior-level responsibilities, and to develop the formative American College of Surgeons Senior Resident Readiness Assessment (ACS SRRA) Program.The American College of Surgeons (ACS) education leadership team conducted a focus group with surgical experts to identify the content for an assessment tool to evaluate senior residents' readiness for their increased levels of responsibility. After the focus group, national experts were recruited to develop consensus on the topics through three rounds of surveys using Delphi methodology. The Delphi participants rated topics using Likert-type scales and their comments were incorporated into subsequent rounds. Consensus was defined as ≥ 80% agreement with internal-consistency reliability (Cronbach's alpha) ≥ 0.8. In a stepwise fashion, topics that did not achieve consensus for inclusion were removed from subsequent survey rounds.The surveys were administered via an online questionnaire.Twelve program directors and assistant program directors made up the focus group. The 39 Delphi participants represented seven different surgical subspecialties and were from diverse practice settings. The median length of experience in general surgery resident education was 20 years (IQR 14.3-30.0) with 64% of the experts being either current or past general surgery residency program directors.The response rate was 100% and Cronbach's alpha was ≥ 0.9 for each round. The Delphi participants contributed a large number of comments. Of the 201 topics that were evaluated initially, 120 topics in 25 core clinical areas were included to create the final domains of ACS SRRA.National consensus on the domain of the ACS SRRA has been achieved via the modified Delphi method among expert surgeon educators. ACS SRRA will identify clinical topics and areas in which each senior resident needs improvement and provide data to residents and residency programs to develop individualized learning plans. This would help in preparing the senior residents to assume their responsibilities and support their readiness for future fellowship training or surgical practice.

Pulmonary valve replacement (PVR) with right ventricular outflow tract (RVOT) reconstruction is a common congenital cardiac operation. Porcine submucosal intestinal-derived extracellular matrix (ECM) patches have been used for RVOT reconstruction. We present 2 adult patients with Tetralogy of Fallot who underwent PVR with RVOT reconstruction utilizing ECM. Both cases required reoperation due to patch dehiscence causing a large paravalvular leak. One patient also had a pseudoaneurysm associated with ECM dehiscence. There may be a propensity for ECM dehiscence in this application and, based on these cases, we recommend avoidance of ECM in RVOT reconstruction with PVR. PVR patients repaired with ECM should be monitored for this complication.

Classic classroom education emphasizes the teacher imparting knowledge, experience, or wisdom (pedagogy). Adult educational theory indicates learning is optimized in an experiential setting, where the learner prepares, the session is case based, and the responsibility of the educator is to teach what the learner does not know. This is referred to as "flipping the classroom." Flipping the classroom is not simple, as the historical educational culture often changes; and, at least early in the transition process, different expectations, preparation, or training are essential for both the learner and educator for this approach to be effective.

Surgical education in 2019 faces may challenges to maintain the high standards of excellence achieved in prior generations of learners and trainers in cardiothoracic surgery. This compendium hopes to review the current and future strategies in surgical education. The topics include the adult learner, assessing competence, providing formative feedback, developing strategies to minimize implicit bias, optimizing education in the operating room, effective classroom teaching, the future of e-learning, the alternative curriculum, teaching mentorship and coaching, deliberate practice and simulation, faculty development, the potential roles of virtual and augmented reality, and the impact artificial intelligence might have on surgical education in the future.

To identify predictors of morbidity and mortality in patients undergoing either transcatheter pulmonary valve replacement (TPVR) or surgical pulmonary valve replacement (SPVR) in an effort to quantify any early benefit of TPVR over SPVR.Using a risk-adjusted propensity score model, we compare early major morbidity and mortality between patients undergoing SPVR and TPVR at our institution between January 2006 and January 2014.145 patients in the SPVR cohort and 78 patients in the TPVR cohort were included. Primary pulmonary regurgitation was more common in the SPVR group (76.6% vs 23.1%, p0.001) and primary pulmonary stenosis was more common in the TPVR group (9.7% vs 44.9%, p0.001). In unadjusted analysis, major morbidity and mortality occurred in 11.7% of SPVR patients versus 3.8% of TPVR patients (p=0.04). However, following risk adjustment and inclusion of a propensity score, no significant difference was seen between the two modalities. A larger right ventricular end-diastolic dimension (RVEDVI) was the only preoperative variable associated with the primary end point (OR 1.013/10 mL/mFollowing risk adjustment, no significant differences were observed between SPVR and TPVR strategies. TPVR was associated with a shorter hospitalisation; however, total hospitalisation costs were similar between groups.

Background The number of adult congenital heart disease (CHD) patients undergoing heart transplantation is increasing rapidly. CHD patients have higher surgical risk at transplantation. High-volume adult CHD transplant centers may have better transplant outcomes. Objectives This study aimed to evaluate the effect of center CHD transplant volume and expertise on transplant outcomes in CHD patients. Methods The authors studied heart transplantations in CHD patients age ≥18 years using the United Network of Organ Sharing (UNOS) database for the primary outcomes of waitlist mortality and post-transplant outcomes at 30 days and 1 year. Transplant centers were assessed by status as the highest CHD transplant volume center in a UNOS region versus all others, presence of Adult Congenital Heart Association accreditation, and adult versus pediatric hospital designation. Results Between January of 2000 and June of 2018, 1,746 adult CHD patients were listed for transplant; 1,006 (57.6%) of these underwent heart transplantation. After adjusting for age, sex, listing status, and inotrope requirement, waitlist mortality risk was lower at Adult Congenital Heart Association accredited centers (hazard ratio: 0.730; p = 0.020). Post-transplant 30-day mortality was lower at the highest volume CHD transplant center in each UNOS region (hazard ratio: 0.706; p = 0.014). Conclusions Designated expertise in CHD care is associated with improved waitlist outcomes for CHD patients listed for transplantation. Post-transplant survival was improved at the highest volume regional center. These findings suggest a possible advantage of regionalization of CHD transplantation.

Classic classroom education emphasizes the teacher imparting knowledge, experience, or wisdom (pedagogy). Adult educational theory indicates learning is optimized in an experiential setting, where the learner prepares, the session is case based, and the responsibility of the educator is to teach what the learner does not know. This is referred to as "flipping the classroom." Flipping the classroom is not simple, as the historical educational culture often changes; and, at least early in the transition process, different expectations, preparation, or training are essential for both the learner and educator for this approach to be effective.

Background The feasibility and efficacy of a web-based curriculum in supplementing thoracic surgical training was previously shown. However, the impact of curricular participation on validated knowledge tests remains unknown. We compared in-service training examination (ITE) results among trainees, stratified by curricular use. Methods The national online curriculum was implemented in August 2013. We retrospectively reviewed trainees who participated in thoracic surgical training programs in both 2012 to 2013 and 2013 to 2014. Scores from the 2013 and 2014 ITEs were obtained, and curricular usage data were collected from site analytics. Trainees were separated into three groups according to 2013 ITE scores; within each group, changes in score for high- versus low-volume users were compared. Results 187 trainees took the ITE both years, with exposure to the online curriculum during only the second year. High-volume users' scores trended toward greater improvement than scores of low-volume users (+18.2% versus +13.0%, p = 0.199). When stratified by 2013 score, the lowest scoring quartile improved substantially, and the highest scoring quartile improved modestly, regardless of curricular use. However, for those individuals who achieved mid-range scores in 2013, there was a trend toward much greater improvement in score with heavier use of the curriculum (+17.0% versus +7.0%, p = 0.094). Conclusions Among trainees who had access to the novel online curriculum during the second of 2 consecutive years, we evaluated the impact of curricular participation on ITE scores. The effect appears to be most pronounced in individuals with mid-range scores, in whom high curricular use led to the greatest improvement.

Objectives In an effort to stimulate residents and trainers to increase their use of simulation training and the Thoracic Surgery Curriculum, a gamification strategy was developed in a friendly but competitive environment. Methods "Top Gun." Low-fidelity simulators distributed annually were used for the technical competition. Baseline and final video assessments were performed, and 5 finalists were invited to compete in a live setting from 2013 to 2015. "Jeopardy." A screening examination was devised to test knowledge contained in the Thoracic Surgery Curriculum. The top 6 2-member teams were invited to compete in a live setting structured around the popular game show Jeopardy . Results "Top Gun." Over 3 years, there were 43 baseline and 34 final submissions. In all areas of assessment, there was demonstrable improvement. There was increasing evidence of simulation as seen by practice and ritualistic behavior. "Jeopardy." Sixty-eight individuals completed the screening examination, and 30 teams were formed. The largest representation came from the second-year residents in traditional programs. Contestants reported an average in-training examination percentile of 72.9. Finalists reported increased use of the Thoracic Surgery Curriculum by an average of 10 hours per week in preparation. The live competition was friendly, engaging, and spirited. Conclusions This gamification approach focused on technical and cognitive skills, has been successfully implemented, and has encouraged the use of simulators and the Thoracic Surgery Curriculum. This framework may capitalize on the competitive nature of our trainees and can provide recognition of their achievements.

Background Adoption of simulation skills training in cardiothoracic (CT) surgery remains a challenge. This study sought to determine whether a "Top Gun" competition would encourage simulator use and improve technical skills among first-year CT residents. Methods A coronary anastomosis simulation module with instructional video was sent to 96 first-year CT residents in traditional programs who were then invited to participate in a Top Gun competition. Residents uploaded a video recording of their baseline anastomosis using the simulator. After 6 weeks of practice under faculty supervision, each trainee uploaded a final video. All submissions were rated in blinded fashion by three CT surgeons. Twelve components were scored on a 5-point Likert scale (1 = poor; 5 = excellent); also, an overall pass-fail grade was given. Five trainees with the highest final scores were invited to compete at a live Top Gun competition. Results Seventeen trainees submitted a baseline anastomosis video for evaluation; 15 submitted a final video. Overall average scores improved from 3.24 ± 0.61 to 4.01 ± 0.33 ( p p = 0.14). Overall average time (minutes:seconds) decreased from 11:10 (range, 5:56 to 18:58) to 9:04 (range, 5:52 to 16:23; p p Conclusions Focused training results in improved technical skills in vessel anastomosis, especially for residents with lower baseline skills. Simulation, as with any educational endeavor, requires the motivation of the trainee, commitment of the faculty educator, and a defined training curriculum.

Aorto-left atrial fistula (AAF) is rarely encountered in clinical practice, and the early diagnosis can be very challenging. This report describes a unique case of AAF caused by a gunshot injury and the pivotal role of transesophageal echocardiography for diagnosis and assessment.

Web-based curricula provide login data that can be advantageously used to characterize and analyze study habits. We sought to compare thoracic surgical trainee In-Training Examination percentiles with regard to their study habits (ie, cramming), as characterized by curriculum login frequency to the national Web-based Thoracic Surgery Curriculum. Furthermore, we then aimed to characterize the curriculum login frequency of trainees as stratified by their performance on the In-Training Examination and their improvement on the In-Training Examination over subsequent years.We performed a retrospective review of trainees who accessed the curriculum before the 2014 In-Training Examination, with curriculum login data collected from site analytics. Scores were compared between trainees who crammed (≥30% increase in logins in the month before the In-Training Examination) and those who did not. Trainees were stratified on the basis of 2014 In-Training Examination percentile and improvement in percentile from 2013 to 2014 into high, medium, and low scorers and improvers.Of 256 trainees who took the 2014 In-Training Examination, 63 (25%) met criteria as crammers. Crammers increased total study sessions immediately before the In-Training Examination (P .001), but without impact on 2014 In-Training Examination percentile (P = .995) or year-to-year improvement (P = .234). Stratification by In-Training Examination percentile demonstrated that highest scoring trainees used the curriculum more frequently in the final month than medium-range scorers (P = .039). When stratified by extent of year-to-year improvement, those who improved the most accessed the curriculum significantly more often in the last month compared with baseline (P = .040). Moreover, those with greatest improvement logged in more in the final month than those with least improvement (P = .006).Increasing the frequency of study periods on the national Web-based thoracic surgery curriculum before the In-Training Examination may have a unique benefit to trainees who initially score low to allow them to significantly improve their subsequent year In-Training Examination performance.

Durable ventricular assist device (VAD) support is uncommonly employed in adult congenital heart disease and often involves supporting a systemic right ventricle (RV). Ventricular assist device support of a subpulmonic RV is even more unusual.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly with infrequent survival to adulthood. A 57-year-old woman with metabolic syndrome presented to the emergency department with exertional fatigue. Echocardiogram demonstrated an enlarged right coronary

Background Traditionally, cardiothoracic residency programs are 2 or 3 years in length and require the completion of a general surgery residency. Six-year integrated programs (IP) that directly match fourth-year medical students have been recently developed. Our objective was to examine the curricula of traditional 2-year (T2) and 3-year (T3) programs and compare them to the curricula of IP. Methods We requested curricula from the directors of all IP, T2, and T3 programs participating in the 2011 to 2012 match. We compared the median number of months spent on a cardiothoracic (CT) rotation, an adult cardiac rotation, a thoracic rotation, and a congenital rotation, as well as time spent on "other" nonsurgical rotations. Traditional programs were categorized into 1 of 3 pathways: combined cardiothoracic (CCT), adult cardiac (AC), or general thoracic (GT). Results Integrated programs spend more time on general thoracic rotations when compared with CCT-T2, CCT-T3, AC-T2, and AC-T3 pathways ( p = 0.009, p = 0.046, p = 0.001 and p = 0.028, respectively). The IP spend a similar amount of time on CT, adult cardiac, and congenital rotations when compared when 2- and 3-year CCT, AC, and GT pathways. Of note, IP spend significantly more time on "other" nonsurgical rotations than all other pathways ( p Conclusions Integrated programs should not be considered "cardiac pathways" as they spend a significant amount of time on thoracic rotations. Additional nonsurgical rotations provide an opportunity for residents in IP to develop unique skills not currently provided in traditional programs.

OBJECTIVE: To understand how teaching behaviors contribute to simulation-based learning, we used a 7-category educational framework to assess the teaching behaviors used in basic skills training. METHODS: Twenty-four first-year cardiothoracic surgery residents and 20 faculty participated in the Boot Camp vessel anastomosis sessions. A portable chest model with synthetic graft and target vessels and a tissue-based porcine model simulated coronary artery anastomosis. After each 2-hour session on days 1 and 2, residents assessed teaching behaviors of faculty using a 20-item questionnaire based on the 5-point Likert scale. After session on day 1, faculty completed a self-assessment questionnaire. At 3 months, faculty completed self-assessment questionnaires regarding teaching behaviors in simulation and clinical settings. Each questionnaire item represents 1 or more teaching categories: "learning climate," "control of session," "communication of goals," "promoting understanding and retention," "evaluation," "feedback," and "self-directed learning." RESULTS: Generally, resident ratings indicated that faculty showed positive teaching behaviors. Faculty self-assessment ratings were all lower (P

Objective Static 3-dimensional printing is used for operative planning in cases that involve difficult anatomy. An interactive 3D print allowing deliberate surgical practice would represent an advance. Methods Two patients with hypertrophic cardiomyopathy had 3-dimensional prints constructed preoperatively. Stereolithography files were generated by segmentation of chest computed tomographic scans. Prints were made with hydrogel material, yielding tissue-like models that can be surgically manipulated. Septal myectomy of the print was performed preoperatively in the simulation laboratory. Volumetric measures of print and patient resected specimens were compared. An assessment tool was developed and used to rate the utility of this process. Clinical and echocardiographic data were reviewed. Results There was congruence between volumes of print and patient resection specimens (patient 1, 3.5 cm 3 and 3.0 cm 3 , respectively; patient 2, 4.0 cm 3 and 4.0 cm 3 , respectively). The prints were rated useful (3.5 and 3.6 on a 5-point Likert scale) for preoperative visualization, planning, and practice. Intraoperative echocardiographic assessment showed adequate relief of left ventricular outflow tract obstruction (patient 1, 80 mm Hg to 18 mm Hg; patient 2, 96 mm Hg to 9 mm Hg). Both patients reported symptomatic improvement (New York Heart Association functional class III to class I). Conclusions Three-dimensional printing of interactive hypertrophic cardiomyopathy heart models allows for patient-specific preoperative simulation. Resection volume relationships were congruous on both specimens and suggest evidence of construct validity. This model also holds educational promise for simulation of a low-volume, high-risk operation that is traditionally difficult to teach.

Background Since 2010, the Joint Council on Thoracic Surgery Education, Inc (JCTSE) has sponsored an annual "Educate the Educators" (EtE) course. The goal is to provide United States academic cardiothoracic surgeons (CTS) the fundamentals of teaching skills, educational curriculum development, and using education for academic advancement. This report describes the course development and evaluation along with attendee's self-assessment of skills through the first 5 years of the program. Methods The content of this 2½-day course was based on needs assessment surveys of CTS and residents attending annual meetings in 2009. From 2010 to 2014, EtE was offered to all CTS at training programs approved by the Accreditation Council for Graduate Medical Education. Course content was evaluated by using end-of-course evaluation forms. A 5-point Likert scale (1 = poor, 5 = excellent) was used to obtain composite assessment mean scores for the 5 years on course variables, session presentations, and self-assessments. Results With 963 known academic CTS in the United States, 156 (16.3%) have attended, representing 70 of 72 training programs (97%), and 1 international surgeon attended. There were also 7 program coordinators. Ratings of core course contents ranged from 4.4 to 4.8, accompanied with highly complementary comments. Through self-assessment, skills and knowledge in all content areas statistically improved significantly. The effect of the course was evaluated with a follow-up survey in which responders rated the program 4.3 on the usefulness of the information for their career and 3.9 for educational productivity. Conclusions The EtE program offers an excellent opportunity for academic CTS to enhance their teaching skills, develop educational activities, and prepare for academic promotion. With its unique networking and mentorship environment, the EtE program is an important resource in the evolution of cardiothoracic surgical training in the United States.

Background We reviewed our experience with surgical procedures for infective endocarditis (IE) in order to evaluate modern outcomes and objectively examine our institutional preferences, including the use of bioprostheses in intravenous drug users (IVDUs) regardless of age and prompt surgical intervention in patients with either septic cerebral emboli or active infection. Methods Review of medical records was conducted from February 1999 to November 2010. The Social Security Death Index was used to determine death from any cause in the postoperative period. Hospital records were used to identify infectious complications, recurrent endocarditis, and reoperation. Results Sixty-four patients were identified as IVDUs and 133 patients as non-IVDUs. Survival at 30 days, 1 year, 5 years, and 10 years for IVDUs and non-IVDUs was 91.2% versus 93.6%, 77.5% versus 83.0%, 46.7% versus 71.1%, and 41.1% versus 52.0%, respectively. Cox regression analysis identified intravenous drug use as an independent risk factor for diminished survival ( p = 0.03), although not for reoperation (p = 0.95) despite 95.3% of IVDUs receiving bioprostheses versus 73.7% of non-IVDUs (p = 0.0002, Fisher's exact test). Forty-three patients were identified as having preoperative septic cerebral emboli; none had a perioperative hemorrhagic event. Active infection approached significance as an independent risk factor for the composite end point of recurrent IE and perioperative infection (odds ratio 2.8; 95% confidence interval, 0.777 to 10.9 ; p = 0.12, Fisher's exact test). Conclusions Bioprostheses are reasonable for IVDUs undergoing valve replacement for IE regardless of age. Prompt surgical intervention in the setting of septic cerebral emboli is justified; in the setting of active infection it is less clear.

Objective The previous Pexelizumab for Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery I (PRIMO-CABG I) trial (n = 3099) indicated that C5 complement inhibition with pexelizumab might reduce myocardial infarction (MI) and postoperative mortality. PRIMO-CABG II was designed to investigate the safety and efficacy of terminal complement inhibition in reducing perioperative MI and mortality in patients undergoing CABG surgery who have 2 or more predefined preoperative risk factors. Methods PRIMO-CABG II, a randomized, double-blind, placebo-controlled trial, enrolled 4254 patients undergoing CABG with or without valve surgery at 249 hospitals in North America and Western Europe from June 2004 to July 2005. The patients were randomly assigned to receive intravenous pexelizumab or placebo. The primary composite endpoint was the incidence of death or MI within 30 days of randomization. Results The PRIMO-CABG II trial did not meet its prespecified primary endpoint of death or MI at 30 days, the secondary endpoints of death at 30 days, or the development of new or worsening congestive heart failure (relative risk 0.91, 0.82, and 1.01, respectively; P > .05). However, in a combined analysis of both pivotal trials, PRIMO-CABG I and II (n = 7353), death at 30 days was significantly reduced for the greatest risk subset (n = 2156, pexelizumab 5.7% vs placebo 8.1%, P = .024). Furthermore, this mortality reduction persisted throughout the 180-day follow-up period (pexelizumab 11.1% vs placebo 14.4%, P = .036). Conclusions Pexelizumab was associated with a nonsignificant 6.7% reduction in the primary composite endpoint of death or MI at postoperative day 30 in CABG patients enrolled in the PRIMO-CABG II trial, despite the suggestion of a more favorable treatment effect in the previous PRIMO-CABG I trial. However, an exploratory analysis of the combined PRIMO I and II data set using an established predictive risk model showed a mortality benefit for high-risk surgical patients.

Objective We sought to develop a 3D printing based simulator for teaching extended septal myectomy to trainees in cardiothoracic surgery (clinical PGY 4-7). This operation is difficult to teach given generally unfamiliar and highly variable anatomy, limited visibility for the assistant, and significant potential complications. Methods A curriculum utilizing multimedia didactics and 3D print based patient-specific surgical simulation was implemented. Six identical 3D prints were constructed for each of 5 consecutive patients. Pre-operative septal myectomy was performed on each printed heart by an attending surgeon and 5 residents. Model myectomy specimen volumes were measured by liquid displacement. All print resections were videotaped and blindly evaluated by 3 attending surgeons. Pre- and post-test evaluations, and a survey tool were also used to evaluate the curriculum. Results Baseline myectomy resection volumes differed significantly (Attending 15 cm 3 vs Resident 3.1 cm 3 , p 3 /resection (Figure 3; 95% CI 0.37-1.3 cm 3 , p 3 /resection (Figure 4; 95% CI 2.4-4.9 cm 3 , p Conclusions A patient-specific 3D printing based simulation module shows promise as a tool to augment and improve cardiothoracic resident training in septal myectomy. The residents were quickly able to perform resections on par with the attending. Residents rated the simulator favorably. Each resident benefited by xxxxx the anatomy of 5 separate patients.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used in advanced heart failure patients. Despite proven efficacy, optimal timing of LVAD implantation is not well defined. METHODS: Patients receiving an LVAD were prospectively recorded. Laboratory and clinical data were extracted and used to calculate the predicted survival with medical therapy using the Seattle Heart Failure Model (SHFM). This was compared with observed survival, hospital length of stay and timeliness of discharge. RESULTS: We identified 104 patients. Survival with an LVAD vs SHFM predicted survival was 69% vs 11% at 1 year, corresponding to a hazard ratio of 0.17 (p 0.0001). SHFM-estimated 1-year survival with medical therapy increased from 4% in 1997 to 2004 to 25% in 2007‐2008 (p 0.0001). Subgroup analysis of higher vs lower risk LVAD patients showed observed 1-year survival of 83% vs 57% (p 0.04). The lower risk group had a shorter length of stay (46 vs 75 days, p 0.03), along with higher rates of discharge prior to transplant (88% vs 61%, p 0.01) and discharge within 60 days of LVAD placement (77% vs 52%, p 0.03). CONCLUSIONS: The SHFM allows prediction of important features of a patient’s hospital course post-operatively, including length of stay and 1-year survival. Given evidence of improved survival and shorter hospital stay in lower risk patients, earlier LVAD placement based on a prediction model like the SHFM should be considered in advanced heart failure patients. The SHFM may have utility as a virtual control arm for single-arm LVAD trials.

The causal factors of the systemic inflammatory response to cardiopulmonary bypass (CPB) were correctly identified in the early 1990 s: "... activation of complement, coagulation, fibrinolytic, and kallikrein cascades, activation of neutrophils with degranulation and protease enzyme release, oxygen radical production, and the synthesis of various cytokines from mononuclear cells" [Butler 1993]. Why therefore have clinical advances to curb the systemic inflammatory response proven such a disappointment? Part of the problem is that cardiac surgery has never taken intellectual ownership of this issue, borrowing its diagnosis from critical care medicine and failing to define the minimal criteria that should be measured when reporting on the systemic inflammatory response. An evidence based review of the current literature by many of the coauthors on this paper found that the majority of studies on the systemic inflammatory response did not measure a single one of the causal factors listed above - thus hindering our ability to identify mechanisms of causation and identify drug targets [Landis 2008]. A panel of experts convened at the Outcomes XII meeting, Barbados 2008, drafted the present consensus document in order to provide a framework to guide future studies and interdictions of the systemic inflammatory response. Herein, we have recommended: 1) mandatory reporting of minimal CPB and perfusion criteria that may affect outcomes, 2) reporting of a minimal set of causal inflammatory markers linked to adverse sequelae, and 3) reporting of at least one clinical end-point of organ injury, from a list of endpoints and markers of organ injury that balance practicality with clinical meaningfulness. It is our collective belief that this document will serve as a foundation for furthering our understanding of the influence of CPB practice with the systemic inflammatory response by standardizing the reporting of research findings in the peer-reviewed literature.

The diagnosis of constrictive pericarditis (CP) often is elusive due to varied causes with nonspecific clinical findings. Conservative management is difficult and surgical pericardiectomy is sometimes required for diagnosis, as well as therapy. A 78-year-old man presented with dyspnea, peripheral

To assess the health economic impact of perioperative myocardial infarction in a cohort of patients undergoing coronary artery bypass graft surgery.Retrospective cohort analysis using data from hospital bills and uniform billing forms.A total of 147 geographically diverse hospitals in the United States.The study population consisted of 2,102 coronary artery bypass graft surgery patients enrolled in the PRIMO-CABG trial at U.S. sites between January 2002 and February 2003.None.Resource utilization and costs during the index hospitalization and during a 6-month follow-up period were compared between patients who had a myocardial infarction by postoperative day 4 and those who did not. Linear regression was used to examine whether myocardial infarction by day 4 was associated with index hospitalization costs, after adjusting for baseline characteristics. Myocardial infarction occurred in 191 (9.1%) patients undergoing coronary artery bypass graft surgery. Myocardial infarction was associated with a doubling of intensive care unit time (3.5 days among patients with no myocardial infarction and 7.1 days among patients with myocardial infarction, p.01) and a 48% increase in hospital length of stay. Myocardial infarction by day 4 was associated with a 43% increase in hospital costs, a 29% increase in physician service costs, a 41% increase in total costs during the index hospitalization, and a 38% increase in cumulative 6-month costs. After baseline adjustment, myocardial infarction continued to be associated with higher index hospitalization costs.Myocardial infarction following coronary artery bypass graft surgery was associated with a significant increase in intensive care unit time, hospital length of stay, and overall costs, which contributed to greater hospital and physician service costs. Healthcare resource utilization is increased in patients sustaining a myocardial infarction following coronary artery bypass graft surgery.

Background: Severe vascular disease is a relative contraindication to heart transplantation (HTx). We addressed the effect of vascular disease on HTx outcomes.Methods:This is a nonconcurrent cohort study of 402 patients who received HTx at our institution between 1985 and 2004. Pretransplant vascular evaluation included carotid, lower extremity, and renal artery duplex studies, and CTangiogram when indicated. Patients with severe and nontreatable vascular disease were excluded. Patients were divided into Group 1: those with pre-transplant vasculopathy, and Group 2: those without pre-transplant vasculopathy. Group 1 had 24 patients with 25 vascular lesions: 1 aortic dissection, 2 abdominal aortic aneurysm (AAA)’s, 5 carotid artery stenoses, 1 renal artery stenosis, and 16 peripheral vascular lesions. Interventions were performed to 15 lesions prior to HTx and to 2 lesions after HTx.Results:Median follow-up was 5.5 years. Group 1 had higher incidence of ischemic cardiomyopathy (p < 0.001), hypertension (p = 0.028), chronic obstructive pulmonary disease (COPD) (p = 0.004), and smoking history (p < 0.001). There were no differences in sex, hyperlipidemia, diabetes, stroke, or renal dysfunction. Multivariate analysis revealed odds of post-transplant death in Group 1 was 1.4 (95% CI: 0.48—4.1, p = 0.54) times greater than that in Group 2. Cox proportional hazards model for survival showed a 50% increase in the hazard of death in patients with pre-transplant vasculopathy, but without statistical significance. Group 1 had higher incidence of post-transplant stroke (p = 0.001) but no difference in allograft coronary atherosclerosis. Conclusions: Pre-transplant vascular disease seems to have negative effect on outcomes after HTx. Larger scale study is needed for further evaluation. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background The Joint Council on Thoracic Surgical Education was formed in 2008 to improve cardiothoracic education. Resident learning has been a concern as reflected in declining passing rates on the American Board of Thoracic Surgery examinations. The Joint Council on Thoracic Surgical Education piloted a program to determine whether early exposure to a cardiothoracic curriculum through participation in a board review course would improve learning. The purpose of this paper is to report the results of this project. Methods Residents from the incoming classes of traditional 5-2 or 5-3 cardiothoracic training programs were randomly selected to attend a 3-day board review course (University of Utah) in September of their first year. For the 2012 and 2013 classes of cardiothoracic residents, we asked all incoming residents to take the prior spring in-training examination in July of their first year and then take the in-training examination in the spring of their first year. We combined the results of the incoming class of 2012 and 2013 and analyzed the results. Results There were 171 residents who participated in either 2012 or 2013. There were 38 residents (78.9% were men) who attended the board review course and 133 (79.7% men) who did not. Questionnaires completed by the program directors and the residents who took the review course showed a favorable opinion of the program. The number of correct answers on the in-training examination, the percentage correct, and the percentile rank score increased more for the residents who took the review course, but was not statistically significant. When only the general thoracic surgery questions were analyzed, there was a statistically significant increase in the rank change between residents who attended the review course and residents who did not (8.4% increase versus 2.0% decrease, respectively; p = 0.042, Student t test). Conclusions This pilot study established for the first time the baseline level of knowledge of incoming residents assessed by the in-training examination. Participation in a board review type course early in the residency training program may increase learning by cardiothoracic residents, but there was not a clear statistical difference between the two groups. The program was viewed as favorable by both the participating residents and the program directors.

Background Activation of extravascular coagulation has been reported in acute lung injury models of sepsis and acute respiratory distress syndrome. Thrombin, the main effector protease of extravascular coagulation, activates proinflammatory cell types, including macrophages, endothelial cells, and neutrophils, each of which participates in lung ischemia–reperfusion injury. We used hirudin, a potent, specific direct thrombin inhibitor, to define the role of thrombin in lung ischemia–reperfusion injury. Methods Rats were pretreated with hirudin 30 minutes before warm, in situ left lung ischemia and reperfusion. Multiple in vivo assessments of lung injury were determined, and mechanistic studies assessed transcriptional regulation early in reperfusion and proinflammatory protein secretion late in reperfusion. Immunohistochemistry localized thrombin activation. Results Thrombin localized to macrophages and endothelial and epithelial cells early in reperfusion. Hirudin significantly limited lung ischemia–reperfusion injury–induced derangements in vascular permeability and intraalveolar inflammatory cell sequestration, resulting in improved arterial oxygenation after ischemia and 4 hours of reperfusion. The protection was transcriptionally mediated by attenuated activator protein-1 and early growth response-1 transactivation, but not nuclear factor kappa B transactivation. This was associated with reduced chemokine, but not tumor necrosis factor α, secretion late in reperfusion. Conclusions Thrombin promotes lung ischemia–reperfusion injury, as hirudin protected against experimental acute lung injury. Hirudin conferred protection through a mechanism independent of nuclear factor kappa B and tumor necrosis factor α, suggesting that its effects may be mediated by a parallel, synergistic inflammatory pathway through activator protein-1 and early growth response-1.

Objective We sought to evaluate the effects of pexelizumab, a C5 complement inhibitor, on death and myocardial infarction in patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. Methods The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary Artery Bypass Graft surgery trial, a phase III prospective, randomized, double-blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The primary end point was the composite of death, myocardial infarction, or both at postoperative day 30 in patients undergoing coronary artery bypass grafting without valve surgery. Postoperative myocardial infarction was defined as a creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or new Q-wave evidence of myocardial infarction by postoperative day 30. Because patients undergoing coronary artery bypass grafting with a valve procedure were not included in the primary population, separate analysis of death and myocardial infarction was conducted in 218 patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. Results Of the 353 patients randomized to any valve procedure, 106 (61%) underwent combined aortic valve replacement and coronary artery bypass grafting in the pexelizumab treatment group compared with 112 (63%) patients in the placebo group. Coronary artery bypass grafting was performed with 1 or more internal thoracic artery grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179 (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11 (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial infarction 30 days after surgical intervention was identical in the 2 groups, but the study was not designed to detect differences in this cohort of patients. Conclusions Inhibition of complement activation by pexelizumab resulted in a decreased mortality at 180 days among 218 patients who underwent combined aortic valve replacement and coronary artery bypass grafting surgery. Additional studies are warranted to confirm this decrease in mortality with pexelizumab in combined aortic valve replacement and coronary artery bypass grafting procedures.

The causal factors of the systemic inflammatory response to cardiopulmonary bypass (CPB) were correctly identified in the early 1990 s: "... activation of complement, coagulation, fibrinolytic, and kallikrein cascades, activation of neutrophils with degranulation and protease enzyme release, oxygen radical production, and the synthesis of various cytokines from mononuclear cells" [Butler 1993]. Why therefore have clinical advances to curb the systemic inflammatory response proven such a disappointment? Part of the problem is that cardiac surgery has never taken intellectual ownership of this issue, borrowing its diagnosis from critical care medicine and failing to define the minimal criteria that should be measured when reporting on the systemic inflammatory response. An evidence based review of the current literature by many of the coauthors on this paper found that the majority of studies on the systemic inflammatory response did not measure a single one of the causal factors listed above - thus hindering our ability to identify mechanisms of causation and identify drug targets [Landis 2008]. A panel of experts convened at the Outcomes XII meeting, Barbados 2008, drafted the present consensus document in order to provide a framework to guide future studies and interdictions of the systemic inflammatory response. Herein, we have recommended: 1) mandatory reporting of minimal CPB and perfusion criteria that may affect outcomes, 2) reporting of a minimal set of causal inflammatory markers linked to adverse sequelae, and 3) reporting of at least one clinical end-point of organ injury, from a list of endpoints and markers of organ injury that balance practicality with clinical meaningfulness. It is our collective belief that this document will serve as a foundation for furthering our understanding of the influence of CPB practice with the systemic inflammatory response by standardizing the reporting of research findings in the peer-reviewed literature.

Myocardial injury and dysfunction in acute infarction and during cardiac surgery with cardiopulmonary bypass (CPB) are associated with an undesirable systemic inflammatory response, in which the complement cascade plays a major role. In animal models C5 inhibition has been found to significantly reduce myocardial infarct size and decrease cellular necrosis and apoptosis. Pexelizumab (Alexion Pharmaceuticals, Inc., Cheshire, CT, USA) is a humanized, monoclonal, single-chain antibody fragment that inhibits C5, thereby blocking its cleavage into active forms. Prospective, randomised, double-blind, placebo-controlled trials using pexelizumab during percutaneous coronary intervention following acute myocardial infarction (AMI), or in patients undergoing coronary artery bypass graft (CABG) with CPB, have demonstrated a reduction in morbidity and mortality. Thus, pexelizumab represents a promising therapeutic option with sustained benefit both in AMI and during CABG with CPB.

Before addressing the question of whether surgeons are ethically obligated to treat Medicare patients despite a substantial reduction in reimbursement, I must make some disclosures. First, as a professor of surgery and chief of the Division of Cardiothoracic Surgery for 25 years, I have worked in an academic medical center my entire career and not in a fee-for-service reward environment. I have had responsibility for the financial viability of the Division of Cardiothoracic Surgery but was only indirectly influenced by reimbursement patterns by private payers, Medicare, or Medicaid. I have not had to directly deal with the issues of increasing practice support expenses, more administrative support needs, or a strict fee-for-service remuneration environment that might affect my salary or the salary of our faculty. Second, some variables based on context and circumstances shade the debate, although at the end of the day, in the predominantly urgent and emergency world of cardiothoracic surgery where healing is the primary end point, such issues should be relatively minor in relevance. First, location of practice and the availability of other specialists can cloud the fundamental ethical imperative and make the decision easier for the urban surgeon to justify not accepting a Medicare patient. One surgeon may be surrounded by many younger surgeons, eagerly trying to develop a sustainable practice, and therefore make the decision to personally withhold care easier. In comparison, the lone practitioner in a smaller, rural practice environment may not have other surgical alternatives and may be under closer local, environmental scrutiny. Therefore, the decision to withhold care based on personal remuneration, if publicized, may be more visible and difficult.

Objective During myocardial ischemia-reperfusion injury, p38 mitogen-activated protein kinase is activated. We examined the effect of a highly specific inhibitor of p38 mitogen-activated protein kinase, FR167653, in an experimental model of regional myocardial ischemia-reperfusion. Methods CD-1 mice received FR167653 intraperitoneally 24 hours before 30 minutes of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion. The p38 mitogen-activated protein kinase activation and kinase activity were determined by Western blotting with monoclonal antibodies for the phosphorylated from of p38 mitogen-activated protein kinase or its substrate, activating transcription factor 2. Nuclear factor κB activity was measured by detecting translocation of nuclear factor κB to the nucleus. The expression of inflammatory cytokines was measured by ribonuclease protection assay. Results Pretreatment of mice with FR167653 before myocardial ischemia-reperfusion resulted in a reduction in p38 mitogen-activated protein kinase phosphorylation (P = .018), an inhibition of p38 mitogen-activated protein kinase activity (P = .047), a smaller amount of nuclear factor κB (P = .001), and a decrease in the expression of inflammatory cytokines (tumor necrosis factor α: P = .023, interleukin 1β: P = .038, monocyte chemotactic protein 1: P = .0001) in the heart and the development of a significantly smaller infarct (P = .0069) relative to hearts from mice treated with vehicle alone. Activation of c-Jun N-terminal kinase and extracellular signal–regulated kinase were observed after myocardial ischemia-reperfusion without inhibition by FR167653. Conclusion We conclude that FR167653 selectively inhibits p38 mitogen-activated protein kinase activation and activity during regional myocardial ischemia-reperfusion injury and efficaciously reduces infarct size (by 73.6%). Thus p38 mitogen-activated protein kinase inhibition may have a role in the treatment of myocardial ischemia-reperfusion.

Initial graft failure, especially in hearts from “marinal” or “expanded” donors, and cardiac allograft asculopathy (CAV), which develops in more than half f transplant recipients who survive beyond 3 to 5 ears, represent the major limitations for the recipients’ hortand long-term survival. The causes for both of hese pathophysiologic processes are largely undefined nd most likely multifactorial; however, activation of he allograft endothelium and the ensuing inflammatory eaction represent early events, serving as potential herapeutic targets (Figure 1). This article initially discusses the pathophysiology of ndothelial activation in cardiac allografts and then ocuses on possible therapeutic strategies to minimize he activation of the endothelium, thereby reducing the ncidence of early and late organ failure.

BackgroundRestoration of blood flow to the ischemic heart may paradoxically exacerbate tissue injury (ischemia/reperfusion injury). Toll-like receptor 4, expressed on several cell types, including cardiomyocytes, is a mediator of the host inflammatory response to infection. Because ischemia/reperfusion injury is characterized by an acute inflammatory reaction, we investigated toll-like receptor 4 activation in a murine model of regional myocardial ischemia/reperfusion injury. We used C3H/HeJ mice, which express a nonfunctional toll-like receptor 4, to assess the pertinence of this receptor to tissue injury after reperfusion of ischemic myocardium.MethodsWild-type mice (C3H/HeN) or toll-like receptor 4 mutant mice (C3H/HeJ) were subjected to 60 minutes of regional myocardial ischemia followed by 2 hours of reperfusion. At the end of reperfusion, the area at risk and the myocardial infarct size were measured as the end point of myocardial ischemia/reperfusion injury. Myocardial mitogen-activated protein kinase activation was measured by Western blotting, and nuclear translocation of nuclear factor-κB and activator protein-1 was determined by electrophoretic mobility shift assay. Ischemia/reperfusion–injured myocardium was also assessed by ribonuclease protection assay for expression of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, monocyte chemotactic factor-1, and interleukin-6).ResultsThe area at risk was similar for all groups after myocardial ischemia/reperfusion injury. There was a 40% reduction in infarct size (as a percentage of the area at risk) in C3H/HeJ mice compared with C3H/HeN mice (P = .001). Within the myocardium, significant activation of c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase was observed in both strains after ischemia and during reperfusion as compared with an absence of mitogen-activated protein kinase activation during sham operations; however, c-Jun N-terminal kinase activity, but not p38 or extracellular signal-regulated kinase activity, was significantly reduced in C3H/HeJ mice (P < .05). In both groups, nuclear factor-κB and activator protein-1 nuclear translocation occurred in the myocardium during myocardial ischemia/reperfusion injury, but, by densitometric analysis, nuclear translocation of nuclear factor-κB and activator protein-1 was significantly decreased in C3H/HeJ mice compared with C3H/HeN mice. Interleukin-1β, monocyte chemotactic factor-1, and interleukin-6 were detectable in reperfused ischemic myocardium but were not detected in sham-operated myocardium; the expression of each of these mediators was significantly decreased in the myocardial tissue of C3H/HeJ mice when compared with expression in the control C3H/HeN mouse strain.ConclusionsOur data suggest that toll-like receptor 4 may mediate, at least in part, myocardial ischemia/reperfusion injury. Inhibition of toll-like receptor 4 activation may be a potential therapeutic target to attenuate ischemia/reperfusion-induced tissue damage in the clinical setting.

Obliterative bronchiolitis (OB) is the main cause of late mortality among long-term survivors of lung transplantation. Although p38 kinase is functional in multiple acute inflammatory injury models, its role in chronic lung rejection is undefined. p38 regulates the expression of the cytokines tumor necrosis (TNF)-alpha and interleukin (IL)-1beta, 2 mediators involved in the development of OB in a tracheal transplant model. These studies assessed whether specific inhibition of p38 with FR167653 (FR) protects against the development of OB in rat tracheal allografts.Rat airways were heterotopically transplanted from Brown-Norway donors into Lewis recipients, and animals were sacrificed on day 14 (6 per group). Treated animals received 10 mg/kg daily of FR intraperitoneally beginning either immediately or at day 7 after transplant. Allografts were assessed by computerized morphometry, and tracheas were processed for TNF-alpha mRNA and protein expression by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Electrophoretic mobility shift assays evaluated nuclear factor kappa beta (NFkappaB) transactivation.Control allografts averaged 61% occlusion and 98% loss of epithelium at 14 days, whereas FR administration reduced luminal occlusion to 28% (p0.001) and epithelial loss to 71% (p0.001). Delayed treatment beginning on day 7 slowed progression of disease, as tracheal occlusion averaged 44% and epithelial loss averaged 80%, both of which were significant (p0.05) improvements relative to 14-day controls. NFkappa transactivation (p0.004) and TNF-alpha mRNA and protein expression were reduced dramatically by FR at 14 days.A specific p38 inhibitor, FR 167653, ameliorates obliterative airway disease in rat tracheal allografts via attenuated NFkappaB transactivation, which ultimately results in diminished TNF-alpha mRNA and protein expression.

The four imaginary charactersDepicted in this story—The mice: “Sniff” and “Scurry,” andThe Littlepeople: “Hem” and “Haw”—Are intended to represent the simple andThe complex parts of ourselves, regardless ofOur age, gender, race or nationalitySometimes we may act likeSniffWho sniffs out change early, orScurryWho scurries into action, orHemWho denies and resists change as he fearsIt will lead to something worse, orHawWho learns to adapt in time when he seesChanging leads to something better!Whatever parts of us we choose to use,We all share something in common:A need to find our way in the mazeAnd succeed in changing times.*

Cardiac surgical procedures, with or without cardiopulmonary bypass, elicit a systemic inflammatory response in patients that induces the elaboration of multiple cytokines, chemokines, adhesion molecules, and destructive enzymes. This inflammatory reaction involves multiple interdependent and redundant cell types and humoral cascades, which allows for amplification and positive feedback at numerous steps. This systemic inflammatory response ultimately results in a broad spectrum of clinical manifestations, with multiple organ failure being the most severe form. Investigative efforts have focused on understanding the mechanism of this systemic inflammatory response syndrome in order to develop potential therapeutic targets to inhibit it, thereby possibly decreasing postoperative morbidity and mortality. Multiple therapeutic methods have been investigated, including pharmacologic inhibitors and modifications of surgical technique and the cardiopulmonary bypass circuit. Although studies have demonstrated that the use of these therapies in experimental and clinical settings has attenuated the systemic inflammatory response, they have failed to conclusively show clinical benefit from these therapies. These therapies may be too specific to minimize the deleterious effects of a systemic inflammatory response that results from the activation of multiple, interdependent, and redundant inflammatory cascades and cell types. Hence, further studies that investigate the molecular and cellular events underlying the systemic inflammatory response syndrome and the resultant effects of anti-inflammatory therapies are warranted to ultimately achieve improvements in clinical outcome after cardiac surgical procedures.

Regulatory cytokines play functional roles in experimental heart, hindlimb, and liver ischemia reperfusion injury. However, little is known about their involvement in direct lung ischemia reperfusion injury (LIRI). These studies were undertaken to investigate the role of two regulatory cytokines, interleukin-4 (IL-4) and IL-10, in an in vivo model of LIRI.Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received either recombinant IL-4 or recombinant IL-10, or antibodies to IL-4 or IL-10 immediately before reperfusion. Lung injury was quantitated by permeability indices, lung parenchymal neutrophil sequestration (myeloperoxidase [MPO] content), and alveolar leukocyte content in bronchoalveolar lavage (BAL) effluent. Expression of IL-4 and IL-10 was determined by immunoblotting, and mRNA expression for early response cytokines was evaluated by ribonuclease protection assays.IL-4 and IL-10 protein expression was significant after 2 hours of reperfusion. Animals receiving anti-IL-4 (p = 0.05) and anti-IL-10 (p = 0.01) antibodies demonstrated increased permeabilities compared with positive controls. Lung tissue neutrophil accumulation (p0.004) and BAL leukocyte content (p0.04) were also significantly increased in animals receiving anti-IL-10 antibodies. Conversely, animals receiving recombinant IL-4 and recombinant IL-10 demonstrated reduced permeabilities and lung MPO content. Both anti-IL-4 and anti-IL-10 treatment increased mRNA expression for a number of early response cytokines, including TNF-alpha and IL-1beta.IL-4 and IL-10 are expressed in response to LIRI and function to decrease injury severity. These effects are partly due to modulated expression of early proinflammatory cytokines.

Peroxynitrite is a potent cytotoxic free radical produced by the reaction of nitric oxide with the superoxide ion produced in conditions of oxidative stress. The purpose of the study was to examine the role of this reactive nitrogen species in lung ischemia-reperfusion injury.Left lungs of male Long-Evans rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received FP-15 (a water-soluble iron containing metalloporphyrin that acts as a peroxynitrite decomposition catalyst). Injury was quantitated in terms of tissue neutrophil accumulation (myeloperoxidase content) and vascular permeability ((125)I bovine serum albumin [BSA] extravasation) and bronchoalveolar lavage cytokine, transcriptional factor and leukocyte content. Separate tissue samples were processed for immunohistology and nuclear protein analysis.Lung vascular permeability was reduced in treated animals by 61% compared with control animals (p0.005). The protective effects of enhanced peroxynitrite decomposition correlated with a 72% reduction in tissue myeloperoxidase content (p0.001) and marked reductions in brochoalveolar lavage leukocyte accumulation. This correlated positively with the diminished expression of pro-inflammatory chemokines and nuclear transcription factors.The deleterious effects of lung ischemia-reperfusion injury are in part mediated by the formation of peroxynitrite, as enhanced decomposition of this species is protective in this model. The development of potent water-soluble decomposition catalysts represents a potentially useful therapeutic tool in the prevention of lung ischemia-reperfusion injury after lung transplantation.