Overcoming the Limits of Reconditioning: Seventeen Hours of EVLP With Successful Transplantation From Uncontrolled Circulatory Death Donor.

BACKGROUND: Uncontrolled donation after circulatory death (DCD) donors are an extraordinary resource to increase the number of lungs available for transplantation. However, the risk of the warm ischemia resulting from cardiac arrest to irreversibly damage the organs is considerable. Moreover, graft preservation issues and organizational problems often worsen the dangerous effects of warm ischemia. Ex vivo lung perfusion (EVLP) enables us to evaluate and recondition lungs whose functionality is doubtful, as well as to overcome the difficulties related to time and logistics. METHODS: We report the case of uncontrolled DCD lungs successfully treated with an exceptionally prolonged EVLP. Because the donor's blood count and liver biopsy showed signs of possible leukemia, EVLP was protracted up to 17 h while waiting for immunohistochemical analyses to rule out this diagnosis; eventually, the results came back negative, and the lungs were judged suitable for transplantation. RESULTS: The recipient was a 32-y-old male individual with cystic fibrosis, colonized by Pandoraea pnomenusa. Bilateral transplantation required central extracorporeal membrane oxygenation. The patient was extubated after 36 h and was discharged 21 d after the operation. Despite early recolonization by Pandoraea pnomenusa and airway complications requiring pneumatic dilatation, he is alive and has a satisfactory respiratory function 15 mo after transplantation. CONCLUSIONS: Uncontrolled DCD represents a challenge due to both logistical issues and the complexity of graft evaluation before procurement. EVLP with cellular perfusate could be a valuable tool to overcome these limits. Nonetheless, caution should be exercised when interpreting the effects of this technique on airway healing.

Echocardiographic assessment of left ventricular function in ex situ heart perfusion using pump-supported and passive afterload working mode: a pilot study.

Ex situ heart perfusion (ESHP) has been developed to decrease cold ischemia time and allow metabolic assessment of donor hearts prior to transplantation. Current clinical ESHP systems preserve the heart in an unloaded condition and only evaluate the cardiac metabolic profile. In this pilot study we performed echocardiographic functional assessment using two alternative systems for left ventricular (LV) loading: pump supported afterload working mode (SAM) and passive afterload working modes (PAM). Six hearts were procured from male Yorkshire pigs. During cold ischemia, hearts were mounted on our custom made ESHP circuit and a 3D-printed enclosure for the performance of echocardiography with a standard TEE probe. Following perfusion with Langherdorf mode of the unloaded heart, the system was switched into different working modes to allow LV loading and functional assessment: pump supported (SAM) and passive (PAM). Echocardiographic assessment of left ventricular function in the donor hearts was performed in vivo and at 1 h of ESHP with SAM, after 4.5 h with PAM and after 5.5 h with SAM. We obtained good quality epicardial echocardiographic images at all time points allowing a comprehensive LV systolic assessment. All indices showed a decrease in LV systolic function throughout the trial with the biggest drop after heart harvesting. We demonstrated the feasibility of echocardiographic functional assessment during ESHP and two different working modes. The expected LV systolic dysfunction consisted of a reduction in EF, FAC, FS, and strain throughout the experiment with the most significant decrease after harvesting.

Evaluation of a Patient-Specific, Low-Cost, 3-Dimensional-Printed Transesophageal Echocardiography Human Heart Phantom.

OBJECTIVE: Currently available 3-dimensional (3D) modeling and printing techniques allow for the creation of patient-specific models based on 3D medical imaging data. The authors hypothesized that a low-cost, patient-specific, cardiac computed tomography-based phantom, created using desktop 3D printing and casting, would have comparable image quality, accuracy, and usability to an existing commercially available echocardiographic phantom. DESIGN: Blinded comparative study. SETTING: Simulation laboratory at a single academic institution. PARTICIPANTS: Voluntary cardiac anesthesiologists at a single academic institution. INTERVENTIONS: Stage 1 of the study consisted of an online questionnaire in which a set of basic transesophageal echocardiography (TEE) views obtained from the 3D printed phantom and commercial phantom were presented to participants, who had to identify the views and evaluate their fidelity to clinical images on a Likert scale. In stage 2, participants performed an unblinded basic TEE examination on both phantoms. MEASUREMENTS AND MAIN RESULTS: The time needed to acquire each basic view was recorded. Overall usability of the phantoms was assessed through a questionnaire. The participants could recognize most of the views. Fidelity ratings for both phantoms were similar (p < 0.05), with the exception of a midesophageal 2-chamber view that was observed better on the 3D printed phantom. The time required to obtain the views was shorter for the 3D printed phantom, although not statistically significant for most views. The overall user experience was better for the 3D phantom for all categories examined (p < 0.05). CONCLUSIONS: The study suggested that a 3D-printed TEE phantom is comparable with the commercially available one with good usability.

Aortic root changes before and after surgery for chronic aortic dilatation: A 3D echocardiographic study.

BACKGROUND: Quantitative 3D assessment of the aortic root may improve planning and success of aortic valve (AV)-sparing operations. AIMS: To use 3D transesophageal echocardiography (TEE) to assess the effect of chronic aortic dilatation on aortic root shape and aortic regurgitation (AR) severity and to examine the effects of AV-sparing operations. METHODS AND RESULTS: To determine the changes with chronic aortic dilatation, we studied 48 patients, 23 with aortic dilatation (Group 1 ≤ mild AR, n = 13; Group 2 ≥ moderate AR, n = 10) and 25 Controls. To determine the changes in AV-sparing operations, a subgroup of 15 patients were examined pre- and post surgery. 3D-TEE images were analyzed using multiplanar reconstruction (QLAB, Philips, Philips Medical Systems, Andover, MA, USA) to obtain aortic root areas, diameters, and lengths. We also calculated a novel parameter called total coaptation surface area (TCoapSA), which sums the contact surface area of all the AV cusps. Compared to Controls, Groups 1 and 2 had significantly larger aortic root areas, inter-commissural distances, and cusp heights. Compared to Group 1 and Controls, Group 2 had significantly smaller TCoapSA when adjusted for aortic annular area (P = 0.001) with shorter coaptation height (P < 0.001). In patients undergoing AV-sparing surgery, TCoapSA was significantly larger post surgery (P = 0.001) with greater coaptation height (P < 0.001) and smaller inter-commissural distances (P < 0.001). CONCLUSIONS: The aortic valve is a dynamic structure that remodels in response to aortic dilatation. Successful valve-sparing surgery corrects these changes. Quantitative modeling of the aortic valve and root could potentially improve the repair to the individual patients and modify outcomes.

Thrombosis prophylaxis in pediatric liver transplantation: A systematic review.

AIM: To review current literature of thrombosis prophylaxis in pediatric liver transplantation (PLT) as thrombosis remains a critical complication. METHODS: Studies were identified by electronic search of MEDLINE, EMBASE and Cochrane Library (CENTRAL) databases until March 2018. The search was supplemented by manually reviewing the references of included studies and the references of the main published systematic reviews on thrombosis and PLT. We excluded from this review case report, small case series, commentaries, conference abstracts, papers which describing less than 10 pediatric liver transplants/year and articles published before 1990. Two reviewers performed study selection independently, with disagreements solved through discussion and by the opinion of a third reviewer when necessary. RESULTS: Nine retrospective studies were included in this review. The overall quality of studies was poor. A pooled analysis of results from studies was not possible due to the retrospective design and heterogeneity of included studies. We found an incidence of portal vein thrombosis (PVT) ranging from 2% to 10% in pediatric living donor liver transplantation (LDLT) and from 4% to 33% in pediatric deceased donor liver transplantation (DDLT). Hepatic artery thrombosis (HAT) was observed mostly in mixed LDLT and DDLT pediatric population with an incidence ranging from 0% to 29%. In most of the studies Doppler ultrasonography was used as a first line diagnostic screening for thrombosis. Four different surgical techniques for portal vein anastomosis were reported with similar efficacy in terms of PVT reduction. Reduced size liver transplant was associated with a low risk of both PVT (incidence 4%) and HAT (incidence 0%, P < 0.05). Similarly, aortic arterial anastomosis without graft interposition and microsurgical hepatic arterial reconstruction were associated with a significant reduced HAT incidence (6% and 0%, respectively). According to our inclusion and exclusion criteria, we did not find eligible studies that evaluated pharmacological prevention of thrombosis. CONCLUSION: Poor quality retrospective studies show the use of tailored surgical strategies might be useful to reduce HAT and PVT after PLT; prospective studies are urgently needed.

Description of a Novel Set-up for Functional Echocardiographic Assessment of Left Ventricular Performance During Ex Vivo Heart Perfusion.

Ex vivo heart perfusion (EVHP) is a new technology aimed at decreasing cold ischemia time and evaluating cardiac function before transplanting a donor heart. In an experimental EVHP swine model, we tested a 3D-printed custom-made set-up to perform surface echocardiography on an isolated beating heart during left ventricular loading. The views obtained at any time point were equivalent to standard transesophageal and transthoracic views. A decrease in left ventricular function during EVHP was observed in all experiments.

A New Multi-Mode Perfusion System for Ex Vivo Heart Perfusion Study.

Ex vivo heart perfusion has been shown to be an effective means of facilitating the resuscitation and assessment of donor hearts for cardiac transplantation. Over the last ten years however, only a few ex vivo perfusion systems have been developed for this application. While results have been promising, a system capable of facilitating multiple perfusion strategies on the same platform has not yet been realized. In this paper, the design, development and testing of a novel and modular ex vivo perfusion system is described. The system is capable of operating in three unique primary modes: the traditional Langendorff Mode, Pump-Supported Working-Mode, and Passive Afterload Working-Mode. In each mode, physiological hemodynamic parameters can be produced by managing perfusion settings. To evaluate heart viability, six experiments were conducted using porcine hearts and measuring several parameters including: pH, aortic pressure, lactate metabolism, coronary vascular resistance (CVR), and myocardial oxygen consumption. Pressure-volume relationship measurements were used to assess left ventricular contractility in each Working Mode. Hemodynamic and metabolic conditions remained stable and consistent across 4 h of ex vivo heart perfusion on the ex vivo perfusion system, validating the system as a viable platform for future development of novel preservation and assessment strategies.

Spontaneous Breathing during Extracorporeal Membrane Oxygenation in Acute Respiratory Failure.

BACKGROUND: We evaluate the clinical feasibility of spontaneous breathing on extracorporeal membrane oxygenation and the interactions between artificial and native lungs in patients bridged to lung transplant or with acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome. METHODS: The clinical course of a total of 48 patients was analyzed. Twenty-three of 48 patients were enrolled in the prospective study (nine bridged to lung transplant, six COPD, and eight acute respiratory distress syndrome). The response to the carbon dioxide removal was evaluated in terms of respiratory rate and esophageal pressure swings by increasing ("relief" threshold) and decreasing ("distress" threshold) the extracorporeal membrane oxygenation gas flow, starting from baseline condition. RESULTS: Considering all 48 patients, spontaneous breathing extracorporeal membrane oxygenation was performed in 100% bridge to lung transplant (9 of 9 extubated), 86% COPD (5 of 6 extubated), but 27% acute respiratory distress syndrome patients (6 of 8 extubated; P < 0.001) and was maintained for 92, 69, and 38% of the extracorporeal membrane oxygenation days (P = 0.021), respectively. In all the 23 patients enrolled in the study, gas flow increase (from 2.3 ± 2.2 to 9.2 ± 3.2 l/min) determined a decrease of both respiratory rate (from 29 ± 6 to 8 ± 9 breaths/min) and esophageal pressure swings (from 20 ± 9 to 4 ± 4 cm H2O; P < 0.001 for all). All COPD and bridge to lung transplant patients were responders (reached the relief threshold), while 50% of acute respiratory distress syndrome patients were nonresponders. CONCLUSIONS: Carbon dioxide removal through extracorporeal membrane oxygenation relieves work of breathing and permits extubation in many patients, mainly bridge to lung transplant and COPD. Only few patients with acute respiratory distress syndrome were able to perform the spontaneous breathing trial, and in about 50% of these, removal of large amount of patient's carbon dioxide production was not sufficient to prevent potentially harmful spontaneous respiratory effort.

A standardized model of brain death, donor treatment, and lung transplantation for studies on organ preservation and reconditioning.

BACKGROUND: We set a model of brain death, donor management, and lung transplantation for studies on lung preservation and reconditioning before transplantation. METHODS: Ten pigs (39.7 ± 5.9 Kg) were investigated. Five animals underwent brain death and were treated as organ donors; the lungs were then procured and cold stored (Ischemia). Five recipients underwent left lung transplantation and post-reperfusion follow-up (Graft). Cardiorespiratory and metabolic parameters were collected. Lung gene expression of cytokines (tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interferon gamma (IFNγ), high mobility group box-1 (HMGB-1)), chemokines (chemokine CC motif ligand-2 (CCL2-MCP-1), chemokine CXC motif ligand-10 (CXCL-10), interleukin-8 (IL-8)), and endothelial activation markers (endothelin-1 (EDN-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), selectin-E (SELE)) was assessed by real-time polymerase chain reaction (PCR). RESULTS: Tachycardia and hypertension occurred during brain death induction; cardiac output rose, systemic vascular resistance dropped (P < 0.05), and diabetes insipidus occurred. Lung-protective ventilation strategy was applied: 9 h after brain death induction, PaO2 was 192 ± 12 mmHg at positive end-expiratory pressure (PEEP) 8.0 ± 1.8 cmH2O and FiO2 of 40%; wet-to-dry ratio (W/D) was 5.8 ± 0.5, and extravascular lung water (EVLW) was 359 ± 80 mL. Procured lungs were cold-stored for 471 ± 24 min (Ischemia) at the end of which W/D was 6.1 ± 0.9. Left lungs were transplanted and reperfused (warm ischemia 98 ± 14 min). Six hours after controlled reperfusion, PaO2 was 192 ± 23 mmHg (PEEP 8.7 ± 1.5 cmH2O, FiO2 40%), W/D was 5.6 ± 0.4, and EVLW was 366 ± 117 mL. Levels of IL-8 rose at the end of donor management (BD, P < 0.05); CCL2-MCP-1, IL-8, HMGB-1, and SELE were significantly altered after reperfusion (Graft, P < 0.05). CONCLUSIONS: We have set a standardized, reproducible pig model resembling the entire process of organ donation that may be used as a platform to test in vivo and ex vivo strategies of donor lung optimization before transplantation.