Publications by authors named "Mark E Roeser"

18 Publications

  • Page 1 of 1

Secondary Burn Progression Mitigated by an Adenosine 2A Receptor Agonist.

J Burn Care Res 2021 Mar 26. Epub 2021 Mar 26.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA.

Background: Current burn therapy is largely supportive with limited therapies to curb secondary burn progression. Adenosine 2A receptor (A2AR) agonists have anti-inflammatory effects with decreased inflammatory cell infiltrate and release of pro-inflammatory mediators. Using a porcine comb burn model, we examined whether A2AR agonists could mitigate burn progression.

Study Design: Eight full-thickness comb burns (4 prongs with 3 spaces per comb) per pig were generated with the following specifications: temperature 115° C, 3 kg force, and 30 second application time. In a randomized fashion, animals (4 per group) were then treated with A2AR agonist (ATL-1223, 3 ng/kg/min, intravenous infusion over 6 hours) or vehicle control. Necrotic interspace development was the primary outcome and additional histologic assessments were conducted.

Results: Analysis of unburned interspaces (72 per group) revealed that ATL-1223 treatment decreased the rate of necrotic interspace development over the first 4 days following injury (p<0.05). Treatment significantly decreased dermal neutrophil infiltration at 48 hours following burn (14.63±4.30 vs 29.71±10.76 neutrophils/high-power field, p=0.029). Additionally, ATL-1223 treatment was associated with fewer interspaces with evidence of microvascular thrombi through post-burn day 4 (18.8% vs 56.3%, p=0.002). Two weeks following insult, the depth of injury at distinct burn sites (adjacent to interspaces) was significantly reduced by ATL-1223 treatment (2.91±0.47 vs 3.28±0.58 mm, p=0.038).

Conclusion: This work demonstrates the ability of an A2AR agonist to mitigate burn progression through dampening local inflammatory processes. Extended dosing strategies may yield additional benefit and improve cosmetic outcome in those with severe injury.
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http://dx.doi.org/10.1093/jbcr/irab053DOI Listing
March 2021

Two Hours of In Vivo Lung Perfusion Improves Lung Function in Sepsis-Induced Acute Respiratory Distress Syndrome.

Semin Thorac Cardiovasc Surg 2021 Mar 11. Epub 2021 Mar 11.

Department of Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Sepsis is the leading cause of acute respiratory distress syndrome (ARDS) in adults and carries a high mortality. Utilizing a previously validated porcine model of sepsis-induced ARDS, we sought to refine our novel therapeutic technique of in vivo lung perfusion (IVLP). We hypothesized that 2 hours of IVLP would provide non-inferior lung rehabilitation compared to 4 hours of treatment. Adult swine (n = 8) received lipopolysaccharide to develop ARDS and were placed on central venoarterial extracorporeal membrane oxygenation. Animals were randomized to 2 vs 4 hours of IVLP. The left pulmonary vessels were cannulated to IVLP using antegrade Steen solution. After IVLP treatment, the left lung was decannulated and reperfused for 4 hours. Total lung compliance and pulmonary venous gases from the right lung (control) and left lung (treatment) were sampled hourly. Biochemical analysis of tissue and bronchioalveolar lavage was performed along with tissue histologic assessment. Throughout IVLP and reperfusion, treated left lung PaO/FiO ratio was significantly higher than the right lung control in the 2-hour group (332.2 ± 58.9 vs 264.4 ± 46.5, P = 0.01). In the 4-hour group, there was no difference between treatment and control lung PaO/FiO ratio (258.5 ± 72.4 vs 253.2 ± 90.3, P = 0.58). Wet-to-dry weight ratios demonstrated reduced edema in the treated left lungs of the 2-hour group (6.23 ± 0.73 vs 7.28 ± 0.61, P = 0.03). Total lung compliance was also significantly improved in the 2-hour group. Two hours of IVLP demonstrated superior lung function in this preclinical model of sepsis-induced ARDS. Clinical translation of IVLP may shorten duration of mechanical support and improve outcomes.
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http://dx.doi.org/10.1053/j.semtcvs.2021.02.034DOI Listing
March 2021

Longitudinal analysis of National Institutes of Health funding for academic thoracic surgeons.

J Thorac Cardiovasc Surg 2021 Feb 3. Epub 2021 Feb 3.

Department of Cardiac Surgery, University of Michigan School of Medicine, Ann Arbor, Mich. Electronic address:

Objective: National Institutes of Health (NIH) funding for academic (noncardiac) thoracic surgeons at the top-140 NIH-funded institutes in the United States was assessed. We hypothesized that thoracic surgeons have difficulty in obtaining NIH funding in a difficult funding climate.

Methods: The top-140 NIH-funded institutes' faculty pages were searched for noncardiac thoracic surgeons. Surgeon data, including gender, academic rank, and postfellowship training were recorded. These surgeons were then queried in NIH Research Portfolio Online Reporting Tools Expenditures and Results for their funding history. Analysis of the resulting grants (1980-2019) included grant type, funding amount, project start/end dates, publications, and a citation-based Grant Impact Metric to evaluate productivity.

Results: A total of 395 general thoracic surgeons were evaluated with 63 (16%) receiving NIH funding. These 63 surgeons received 136 grants totaling $228 million, resulting in 1772 publications, and generating more than 50,000 citations. Thoracic surgeons have obtained NIH funding at an increasing rate (1980-2019); however, they have a low percentage of R01 renewal (17.3%). NIH-funded thoracic surgeons were more likely to have a higher professorship level. Thoracic surgeons perform similarly to other physician-scientists in converting K-Awards into R01 funding.

Conclusions: Contrary to our hypothesis, thoracic surgeons have received more NIH funding over time. Thoracic surgeons are able to fill the roles of modern surgeon-scientists by obtaining NIH funding during an era of increasing clinical demands. The NIH should continue to support this mission.
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http://dx.doi.org/10.1016/j.jtcvs.2021.01.088DOI Listing
February 2021

Isolated Lung Perfusion in the Management of Acute Respiratory Distress Syndrome.

Int J Mol Sci 2020 Sep 17;21(18). Epub 2020 Sep 17.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22902, USA.

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource utilization. While our understanding of this disease has improved, the majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. There is a dramatic need for the development and breakthrough of new methods for the treatment of ARDS. Isolated machine lung perfusion is a promising surgical platform that has been associated with the rehabilitation of injured lungs and the induction of molecular and cellular changes in the lung, including upregulation of anti-inflammatory and regenerative pathways. Initially implemented in an ex vivo fashion to evaluate marginal donor lungs prior to transplantation, recent investigations of isolated lung perfusion have shifted in vivo and are focused on the management of ARDS. This review presents current tenants of ARDS management and isolated lung perfusion, with a focus on how ex vivo lung perfusion (EVLP) has paved the way for current investigations utilizing in vivo lung perfusion (IVLP) in the treatment of severe ARDS.
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http://dx.doi.org/10.3390/ijms21186820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555278PMC
September 2020

A 30-year analysis of National Institutes of Health-funded cardiac transplantation research: Surgeons lead the way.

J Thorac Cardiovasc Surg 2020 Jul 5. Epub 2020 Jul 5.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Va. Electronic address:

Objectives: Obtaining National Institutes of Health funding for heart transplant research is becoming increasingly difficult, especially for surgeons. We sought to determine the impact of National Institutes of Health-funded cardiac transplantation research over the past 30 years.

Methods: National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results was queried for R01s using 10 heart transplant-related terms. Principal Investigator, total grant funding amount, number of publications, and citations of manuscripts were collected. A citation-based Grant Impact Metric was assigned to each grant: sum of citations for each manuscript normalized by the funding of the respective grant (per $100K). The department and background degree(s) (MD, PhD, MD/PhD) for each funded Principal Investigator were identified from institutional faculty profiles.

Results: A total of 321 cardiac transplantation R01s totaling $723 million and resulting in 6513 publications were analyzed. Surgery departments received more grants and more funding dollars to study cardiac transplantation than any other department (n = 115, $249 million; Medicine: n = 93, $208 million; Pathology: 26, $55 million). Surgeons performed equally well compared with all other Principal Investigators with respect to Grant Impact Metric (15.1 vs 20.6; P = .19) and publications per $1 million (7.5 vs 6.8; P = .75). Finally, all physician-scientists (MDs) have a significantly higher Grant Impact Metric compared with nonclinician researchers (non-MDs) (22.3 vs 16.3; P = .028).

Conclusions: Surgeon-scientists are equally productive and impactful compared with nonsurgeons despite decreasing funding rates at the National Institutes of Health and greater pressure from administrators to increase clinical productivity.
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http://dx.doi.org/10.1016/j.jtcvs.2020.06.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782209PMC
July 2020

Development and Validation of a Seizure Prediction Model in Neonates After Cardiac Surgery.

Ann Thorac Surg 2021 06 29;111(6):2041-2048. Epub 2020 Jul 29.

Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Electroencephalographic seizures (ESs) after neonatal cardiac surgery are often subclinical and have been associated with poor outcomes. An accurate ES prediction model could allow targeted continuous electroencephalographic monitoring (CEEG) for high-risk neonates.

Methods: ES prediction models were developed and validated in a multicenter prospective cohort where all postoperative neonates who underwent cardiopulmonary bypass (CPB) also underwent CEEG.

Results: ESs occurred in 7.4% of neonates (78 of 1053). Model predictors included gestational age, head circumference, single-ventricle defect, deep hypothermic circulatory arrest duration, cardiac arrest, nitric oxide, extracorporeal membrane oxygenation, and delayed sternal closure. The model performed well in the derivation cohort (c-statistic, 0.77; Hosmer-Lemeshow, P = .56), with a net benefit (NB) over monitoring all and none over a threshold probability of 2% in decision curve analysis (DCA). The model had good calibration in the validation cohort (Hosmer-Lemeshow, P = .60); however, discrimination was poor (c-statistic, 0.61), and in DCA there was no NB of the prediction model between the threshold probabilities of 8% and 18%. By using a cut point that emphasized negative predictive value in the derivation cohort, 32% (236 of 737) of neonates would not undergo CEEG, including 3.5% (2 of 58) of neonates with ESs (negative predictive value, 99%; sensitivity, 97%).

Conclusions: In this large prospective cohort, a prediction model of ESs in neonates after CPB had good performance in the derivation cohort, with an NB in DCA. However, performance in the validation cohort was weak, with poor discrimination, poor calibration, and no NB in DCA. These findings support CEEG of all neonates after CPB.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.157DOI Listing
June 2021

Pulmonary Artery Banding for Children With Dilated Cardiomyopathy: US Experience.

Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2020 ;23:69-76

Baylor College of Medicine and Texas Children's Hospital, Houston, Texas. Electronic address:

Pulmonary artery band placement is a recently described therapeutic strategy for dilated cardiomyopathy with preserved right ventricular function, originally reported from Germany.1 We present the results of the multicenter retrospective study of pulmonary artery band experience in the United States, with comparison to the German experience. Five centers contributed a total 14 patients (median age 5 months, interquartile range 3.5-10). Mechanical ventilation was required in 9/12 (75%) patients and inotropes were used in 13/14 (93%) patients preoperatively. Ultimately, 4 (29%) patients experienced cardiac recovery, 8 (57%) were bridged to cardiac transplantation (6 with ventricular assist device placement), and 2 (14%) died. Although both the US and Germany series demonstrated high prevalence of achieving patients' individual target (either cardiac recovery or transplant), the mode of success was different (recovery rate: <1/3 in the United States and >2/3 in Germany). Lower recovery rate may be a reflection of sicker preoperative status, and thereby a more advanced stage of heart failure (preoperative intubation: >2/3 in the United States vs <1/3 in Germany). Further studies would be warranted to gain more insight into patient selection as well as optimal timing for the intervention.
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http://dx.doi.org/10.1053/j.pcsu.2020.03.002DOI Listing
March 2021

Reduced-flow ex vivo lung perfusion to rehabilitate lungs donated after circulatory death.

J Heart Lung Transplant 2020 01 18;39(1):74-82. Epub 2019 Sep 18.

Departments of Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Background: Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs.

Methods: A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion.

Results: After transplant, left lung-specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 ± 87.7 mm Hg vs. 252.7 ± 166.0 mm Hg, p = 0.017; 4-hour: 429.7 ± 93.6 mm Hg vs. 231.5 ± 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 ± 9.4 ml/cm HO vs. 10.2 ± 3.5 ml/cm HO, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 ± 0.7 vs. 8.8 ± 1.1, p = 0.040) and interleukin-1β expression (927 ± 300 pg/ng protein vs. 2,070 ± 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group.

Conclusions: EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.
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http://dx.doi.org/10.1016/j.healun.2019.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001159PMC
January 2020

Comprehensive National Institutes of Health funding analysis of academic cardiac surgeons.

J Thorac Cardiovasc Surg 2020 06 9;159(6):2326-2335.e3. Epub 2019 Sep 9.

Division of Cardiac Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Va. Electronic address:

Objective: To determine trends in National Institutes of Health (NIH) funding for cardiac surgeons, hypothesizing they are at a disadvantage in obtaining funding owing to intensive clinical demands.

Methods: Cardiac surgeons (adult/congenital) currently at the top 141 NIH-funded institutions were identified using institutional websites. The NIH funding history for each cardiac surgeon was queried using the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER). Total grant funding, publications, and type was collected. Academic rank, secondary degrees, and fellowship information was collected from faculty pages. Grant productivity was calculated using a validated grant impact metric.

Results: A total of 818 academic cardiac surgeons were identified, of whom 144 obtained 293 NIH grants totaling $458 million and resulting in 6694 publications. We identified strong associations between an institution's overall NIH funding rank and the number of cardiac surgeons, NIH grants to cardiac surgeons, and amount of NIH funding to cardiac surgeons (P < .0001 for all). The majority of NIH funding to cardiac surgeons is concentrated in the top quartile of institutions. Cardiac surgeons had a high conversion rates from K awards (mentored development awards) to R01s (6 of 14; 42.9%). Finally, we demonstrate that the rate of all NIH grants awarded to cardiac surgeons has increased, driven primarily by P and U (collaborative project) grants.

Conclusions: NIH-funded cardiac surgical research has had a significant impact over the last 3 decades. Aspiring cardiac surgeon-scientists may be more successful at top quartile institutions owing to better infrastructure and mentorship.
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http://dx.doi.org/10.1016/j.jtcvs.2019.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546359PMC
June 2020

Impact of Complications After Cardiac Operation on One-Year Patient-Reported Outcomes.

Ann Thorac Surg 2020 01 16;109(1):43-48. Epub 2019 Jul 16.

Division of Thoracic & Cardiovascular Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Background: Current reporting on cardiac surgical outcomes focuses on a patient's status at 30 days and lacks long-term meaningful data. The purpose of this study was to determine the impact of complications after cardiac operation on patient-reported outcomes (PROs) at 1 year after surgery.

Methods: All patients undergoing cardiac operation at an academic institution (2014-2015) were contacted 1 year after surgery to obtain vital status, location, and PROs using the validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH-PROMIS). Records were merged with Society of Thoracic Surgeons (STS) data, and multivariate linear regression evaluated the risk-adjusted effects of complications on 1-year PROs.

Results: A total of 782 eligible patients underwent cardiac operation, with PROs data available for 91% of patients alive at 1 year (648 of 716). Mean NIH-PROMIS scores were global physical health (GPH), 48.8 ± 10.2; global mental health (GMH), 51.3 ± 9.5; and physical functioning (PF), 45.5 ± 10.2 (reference score for general adult population, 50 ± 10). Occurrence of an STS Major Morbidity (prolonged ventilation, renal failure, reoperation, stroke, or deep sternal wound infection) significantly reduced 1-year PROs (GPH, 45.4 ± 8.9 [P < .001]; GMH, 48.6 ± 9.5 [P = .01]; PF, 40.9 ± 10.2 [P < .001]). After risk adjustment, incidence of a STS Major Morbidity, prolonged ventilation, or renal failure had a significant adverse effect on 1 or more PRO domains.

Conclusions: Although cardiac surgical patients have PROs scores similar to the general population, complications after cardiac operation continue to negatively influence patient quality of life 1 year after surgery. Use of NIH-PROMIS shows that prolonged ventilation and renal failure have the largest impact on 1-year patient-reported outcomes.
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http://dx.doi.org/10.1016/j.athoracsur.2019.05.067DOI Listing
January 2020

Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During Extracorporeal Cardiopulmonary Resuscitation.

Ann Surg 2019 06;269(6):1176-1183

Department of Surgery, University of Virginia, Charlottesville, VA.

Objective: We tested the hypothesis that systemic administration of an A2AR agonist will reduce multiorgan IRI in a porcine model of ECPR.

Summary Background Data: Advances in ECPR have decreased mortality after cardiac arrest; however, subsequent IRI contributes to late multisystem organ failure. Attenuation of IRI has been reported with the use of an A2AR agonist.

Methods: Adult swine underwent 20 minutes of circulatory arrest, induced by ventricular fibrillation, followed by 6 hours of reperfusion with ECPR. Animals were randomized to vehicle control, low-dose A2AR agonist, or high-dose A2AR agonist. A perfusion specialist using a goal-directed resuscitation protocol managed all the animals during the reperfusion period. Hourly blood, urine, and tissue samples were collected. Biochemical and microarray analyses were performed to identify differential inflammatory markers and gene expression between groups.

Results: Both the treatment groups demonstrated significantly higher percent reduction from peak lactate after reperfusion compared with vehicle controls. Control animals required significantly more fluid, epinephrine, and higher final pump flow while having lower urine output than both the treatment groups. The treatment groups had lower urine NGAL, an early marker of kidney injury (P = 0.01), lower plasma aspartate aminotransferase, and reduced rate of troponin rise (P = 0.01). Pro-inflammatory cytokines were lower while anti-inflammatory cytokines were significantly higher in the treatment groups.

Conclusions: Using a novel and clinically relevant porcine model of circulatory arrest and ECPR, we demonstrated that a selective A2AR agonist significantly attenuated systemic IRI and warrants clinical investigation.
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http://dx.doi.org/10.1097/SLA.0000000000002685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757347PMC
June 2019

Ex Vivo Assessment of Porcine Donation After Circulatory Death Lungs That Undergo Increasing Warm Ischemia Times.

Transplant Direct 2018 Dec 12;4(12):e405. Epub 2018 Nov 12.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA.

Background: Increased utilization of donation after circulatory death (DCD) lungs may help alleviate the supply/demand mismatch between available donor organs and lung transplant candidates. Using an established porcine DCD model, we sought to determine the effect of increasing warm ischemia time (WIT) after circulatory arrest on lung function during ex vivo lung perfusion (EVLP).

Methods: Porcine donors (n = 15) underwent hypoxic cardiac arrest, followed by 60, 90, or 120 minutes of WIT before procurement and 4 hours of normothermic EVLP. Oxygenation, pulmonary artery pressure, airway pressure, and compliance were measured hourly. Lung injury scores were assessed histologically after 4 hours of EVLP.

Results: After EVLP, all 3 groups met all the criteria for transplantation, except for 90-minute WIT lungs, which had a mean pulmonary artery pressure increase greater than 15%. There were no significant differences between groups as assessed by final oxygenation capacity, as well as changes in pulmonary artery pressure, airway pressure, or lung compliance. Histologic lung injury scores as well as lung wet-to-dry weight ratios did not significantly differ between groups.

Conclusions: These results suggest that longer WIT alone (up to 120 minutes) does not predict worse lung function at the conclusion of EVLP. Expanding acceptable WIT after circulatory death may eventually allow for increased utilization of DCD lungs in procurement protocols.
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http://dx.doi.org/10.1097/TXD.0000000000000845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283086PMC
December 2018

Cardiothoracic and Vascular Surgeons Achieve High Rates of K Award Conversion Into R01 Funding.

Ann Thorac Surg 2018 08 14;106(2):602-607. Epub 2018 Mar 14.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia. Electronic address:

Background: Obtaining National Institutes of Health (NIH) R01 funding remains extremely difficult. The utility of career development grants (K awards) for achieving the goal of R01 funding remains debated, particularly for surgeon-scientists. We examined the success rate for cardiothoracic and vascular (CTV) surgeons compared with other specialties in converting K-level grants into R01 equivalents.

Methods: All K (K08 and K23) grants awarded to surgeons by the NIH between 1992 and 2017 were identified through NIH Research Portfolio Online Report Tools (RePORTER), an online database combining funding, publications, and patents. Only grants awarded to CTV surgeons were included. Grants active within the past year were excluded. Mann-Whitney U tests and χ tests were used to compare groups.

Results: During this period, 62 K grants were awarded to CTV surgeons. The analysis excluded 16 grants that were still active within the last year. Twenty-two (48%) of the remaining K awardees successfully transitioned to an R01 or equivalent grant. Awardees with successful conversion published nine publications per K grant compared with four publications for those who did not convert successfully (p = 0.01). The median time for successful conversion to an R grant was 5.0 years after the K award start date. Importantly, the 10-year conversion rate to R01 was equal for CTV surgeons compared with other clinician-investigators (52.6% vs 42.5%).

Conclusions: CTV surgeons have an equal 10-year conversion rate to the first R01 award compared with other clinicians. These data suggest that NIH achieves a good return on investment when funding CTV surgeon-scientists with K-level funding.
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http://dx.doi.org/10.1016/j.athoracsur.2018.02.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476174PMC
August 2018

In vivo lung perfusion rehabilitates sepsis-induced lung injury.

J Thorac Cardiovasc Surg 2018 01 14;155(1):440-448.e2. Epub 2017 Sep 14.

Department of Surgery, University of Virginia, Charlottesville, Va. Electronic address:

Background: Sepsis is the leading cause of lung injury in adults and can lead to acute respiratory distress syndrome (ARDS). Using a novel technique of isolated in vivo lung perfusion (IVLP), we hypothesized that normothermic IVLP will improve oxygenation and compliance in a porcine model of sepsis-induced lung injury.

Methods: Mature adult swine (n = 8) were administered lipopolysaccharide (LPS; 50 μg/kg over 2 hours) via the external jugular vein, followed by sternotomy and central extracorporeal membrane oxygenation (ECMO) cannulation (right atrium to ascending aorta). The left pulmonary artery (inflow) and left superior and inferior pulmonary veins (outflow) were dissected out and cannulated to deliver isolated perfusion to the left lung. After 4 hours of normothermic IVLP with Steen solution, the left lung then underwent 4 hours of reperfusion after IVLP decannulation. Airway pressures and lung-specific pulmonary vein blood gases from the right lung (LPS control) and left lung (LPS + IVLP) of the same animal were compared.

Results: All animals demonstrated a significant reduction in the ratio of partial pressure of oxygen in arterial blood (PaO)/fraction of inspired oxygen (FiO) (P/F ratio) and total lung compliance at 2 hours after the start of LPS infusion (mean, 469 ± 19.7 mm Hg vs 222.2 ± 21.4 mm Hg; P < .0001). After reperfusion, 6 animals (75%) exhibited improved lung function, allowing for ECMO decannulation. Lung-specific oxygenation was superior in the left lung after 4 hours of reperfusion (mean, 310.5 ± 54.7 mm Hg vs 201.1 ± 21.7 mm Hg; P = .01). Similarly, total lung compliance improved after IVLP of the left lung. The lung wet weight to dry weight ratio demonstrated reduced edema in rehabilitated left lungs (mean, 6.5 ± 0.3 vs 7.5 ± 0.4; P = .04).

Conclusions: IVLP successfully rehabilitated LPS-injured lungs compared to ECMO support alone in this preclinical porcine model.
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http://dx.doi.org/10.1016/j.jtcvs.2017.08.124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744259PMC
January 2018

Ex Vivo Lung Perfusion Rehabilitates Sepsis-Induced Lung Injury.

Ann Thorac Surg 2017 Jun 21;103(6):1723-1729. Epub 2017 Apr 21.

Department of Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Background: Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation and may expand the use of marginal organs for transplantation. We hypothesized that 4 hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury.

Methods: We used intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response in a porcine model of lung injury. Two groups of 4 animals each received a 2-hour infusion of LPS through the external jugular vein. Serial measurements of blood gases were performed every 30 minutes until the partial pressure of oxygen/fraction of inspired oxygen ratio dropped below 150 on two consecutive readings. Lungs were then randomized to treatment with 4 hours of normothermic EVLP with STEEN Solution (XVIVO Perfusion Inc, Englewood, CO) or 4 additional hours of in vivo perfusion (control). Airway pressures and blood gases were recorded for calculation of dynamic lung compliance and partial pressure of oxygen/fraction of inspired oxygen ratios. EVLP was performed with hourly recruitment maneuvers and oxygen challenge.

Results: All animals reached a partial pressure of oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg within 3 hours after start of the LPS infusion. Oxygenation and compliance in the control animals continued to decline during the 4-hour in vivo perfusion period, and 3 of the 4 animals died of severe hypoxia within 4 hours. The EVLP group demonstrated significant improvements hour 1 to hour 4 in oxygenation (365.8 ± 53.0 vs 584.4 ± 21.0 mm Hg, p = 0.02) and dynamic compliance (9.0 ± 2.8 vs 15.0 ± 3.6, p = 0.02 mL/cm HO).

Conclusions: EVLP successfully rehabilitated LPS-induced lung injury in this preclinical porcine model and may thus provide a means to rehabilitate many types of acute lung injury.
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http://dx.doi.org/10.1016/j.athoracsur.2017.01.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438908PMC
June 2017

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

J Thorac Cardiovasc Surg 2017 01 22;153(1):197-204. Epub 2016 Sep 22.

Department of Surgery, University of Virginia, Charlottesville, Va. Electronic address:

Objective: Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation.

Methods: Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured.

Results: Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm HO vs 15.0 ± 4.6 mL/cm HO) and 4 hours (30.6 ± 1.3 mL/cm HO vs 17.7 ± 5.9 mL/cm HO) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion.

Conclusions: Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.
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http://dx.doi.org/10.1016/j.jtcvs.2016.09.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164862PMC
January 2017

Invited Commentary.

Authors:
Mark E Roeser

Ann Thorac Surg 2016 08;102(2):572

University of Virginia, PO Box 800679, Charlottesville, VA22908. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2016.03.001DOI Listing
August 2016

Descending Aortic Translocation for Relief of Distal Tracheal and Proximal Bronchial Compression.

Ann Thorac Surg 2016 Sep 19;102(3):859-862. Epub 2016 May 19.

Division of Congenital Heart Surgery, Texas Children's Hospital; Michael E. DeBakey Department of Surgery, Baylor College of Medicine; Houston, Texas.

Background: A descending thoracic aorta that traverses the midline is an uncommon cause of airway compression affecting the distal trachea and proximal main bronchi. Posterior aortopexy has had inconsistent results.

Methods: A retrospective review determined that, since 2004, 5 children have undergone descending aortic translocation at Texas Children's Hospital. The average age at the time of surgical treatment was 4.2 years, and all patients presented with recurring respiratory illness requiring hospitalization. All patients had preoperative imaging (4 patients with computed tomography scans and 1 with magnetic resonance imaging) confirming a compromised airway caused by a midline aorta, and 4 of the 5 patients had perioperative bronchoscopy. Three patients had a right-dominant double aortic arch. Descending aortic translocation was performed through a midline sternotomy with cardiopulmonary bypass and deep hypothermia. The proximal descending aorta was transected distal to the subclavian artery, brought up through the transverse sinus caudad to the tracheal carina and pulmonary artery, and anastomosed in an end-to-side fashion to the ascending aorta.

Results: Mean cardiopulmonary bypass was 144.8 ± 32.6 minutes, with an aortic cross-clamp time of 59 ± 40.9. Absence of perfusion to the descending thoracic aorta averaged 44.4 ± 13.7 minutes. Concomitant procedures were performed in 4 of the 5 patients. At a median follow-up of 26 months (range, 3 to 101 months), all patients had resolution of symptoms.

Conclusions: A midline descending aorta can cause compression of the tracheal carina and proximal bronchi, with debilitating symptoms. Translocation of the descending aorta is a reliable procedure that relieves the compression and results in long-term resolution of symptoms.
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http://dx.doi.org/10.1016/j.athoracsur.2016.02.044DOI Listing
September 2016
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