Strategies to prolong homeostasis of ex vivo perfused lungs Takahashi, Mamoru; Andrew Cheung, Hei Yu; Watanabe, Tatsuaki ...
The Journal of thoracic and cardiovascular surgery,
June 2021, 2021-Jun, 2021-06-00, 20210601, Letnik:
161, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Ex vivo lung perfusion provides an innovative method to assess and repair donor lungs. The current Toronto ex vivo lung perfusion protocol can reliably and reproducibly preserve lungs for 12 hours. A ...longer ex vivo lung perfusion preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24-hour normothermic ex vivo lung perfusion.
We systematically examined 3 modifications of ex vivo lung perfusion perfusate administration in a large animal 24-hour ex vivo lung perfusion model. Pig lungs were assigned to 4 groups (n = 5 per group): (1) control; (2) continuous replacement of ex vivo lung perfusion perfusate; (3) modified feed, which used a modified solution to maintain perfusate osmolality by adjusting glucose and sodium levels; and (4) total parenteral nutrition, in which we added parenteral nutrition to the perfusate.
Only 1 lung in the control group completed 24-hour ex vivo lung perfusion. However, 24-hour perfusion was achieved in 4 lungs in the continuous replacement group, 3 lungs in the modified feed group, and 4 lungs in the total parenteral nutrition group. The total parenteral nutrition group achieved significantly longer stable perfusion time compared with control (P = .03). Lung function was significantly improved and inflammatory cytokine production was reduced in the continuous replacement and total parenteral nutrition groups compared with control.
Modifications of ex vivo lung perfusion perfusate toward achieving a stable homeostatic state can extend perfusion time for up to 24 hours. Although these modifications allow for prolonged ex vivo lung perfusion, further research will be required to develop stable lung support beyond 24 hours.
Three modifications of EVLP perfusate administration in a pig 24-hour EVLP model. The TPN group achieved significantly longer stable perfusion time compared with control (P = .03). The dotted lines represent 95% confidence interval. Display omitted
Availability of organs is a limiting factor for lung transplantation, leading to substantial mortality rates on the wait list. Use of organs from donors with transmissible viral infections, such as ...hepatitis C virus (HCV), would increase organ donation, but these organs are generally not offered for transplantation due to a high risk of transmission. Here, we develop a method for treatment of HCV-infected human donor lungs that prevents HCV transmission. Physical viral clearance in combination with germicidal light-based therapies during normothermic ex-vivo Lung Perfusion (EVLP), a method for assessment and treatment of injured donor lungs, inactivates HCV virus in a short period of time. Such treatment is shown to be safe using a large animal EVLP-to-lung transplantation model. This strategy of treating viral infection in a donor organ during preservation could significantly increase the availability of organs for transplantation and encourages further clinical development.
Acceptance of lungs from donation after circulatory determination of death has been generally restricted to donors who have cardiac arrest within 60 minutes after withdrawal of life-sustaining ...therapies. We aimed to determine the effect of the interval between withdrawal of life-sustaining therapies to arrest and recipient outcomes. Second, we aimed to compare outcomes between donation after circulatory determination of death transplants and donation after neurologic determination of death transplants.
A single-center, retrospective review was performed analyzing the clinical outcomes of transplant recipients who received donation after circulatory determination of death lungs and those who received donation after neurologic determination of death lungs. Donation after circulatory determination of death cases were then grouped on the basis of the interval between withdrawal of life-sustaining therapies and asystole: 0 to 19 minutes (rapid), 20 to 59 minutes (intermediate), and more than 60 minutes (long). Recipient outcomes from each of these groups were compared.
A total of 180 cases of donation after circulatory determination of death and 1088 cases of donation after neurologic determination of death were reviewed between 2007 and 2017. There were no significant differences in the 2 groups in terms of age, gender, recipient diagnosis, and type of transplant (bilateral vs single). Ex vivo lung perfusion was used in 118 of 180 (65.6%) donation after circulatory determination of death cases and 149 of 1088 (13.7%) donation after neurologic determination of death cases before transplantation. The median survivals of recipients who received donation after circulatory determination of death lungs versus donation after neurologic determination of death lungs were 8.0 and 6.9 years, respectively. Time between withdrawal of life-sustaining therapies and asystole was available for 148 of 180 donors (82.2%) from the donation after circulatory determination of death group. Mean and median time from withdrawal of life-sustaining therapies to asystole were 28.6 minutes and 16 minutes, respectively. Twenty donors required more than 60 minutes to experience cardiac arrest, with the longest duration being 154 minutes before asystole was recorded. Recipients of donation after circulatory determination of death lungs who had cardiac arrest at 0 to 19 minutes (90 donors), 20 to 59 minutes (38 donors), and more than 60 minutes (20 donors) did not demonstrate any significant differences in terms of short- and long-term survivals, primary graft dysfunction 2 and 3, intensive care unit stay, mechanical ventilation days, or total hospital stay.
Short- and long-term outcomes in recipients who received donation after neurologic determination of death versus donation after circulatory determination of death lungs are similar. Different withdrawals of life-sustaining therapies to arrest intervals were not associated with recipient outcomes. The maximum acceptable duration of this interval has yet to be established.
A large proportion of controlled donation after circulatory death (cDCD) donor lungs are declined because cardiac arrest does not occur within a suitable time after the withdrawal of life‐sustaining ...therapy. Improved strategies to preserve lungs after asystole may allow the recovery team to arrive after death actually occurs and enable the recovery of lungs from more cDCD donors. The aim of this study was to determine the effect of donor positioning on the quality of lung preservation after cardiac arrest in a cDCD model. Cardiac arrest was induced by withdrawal of ventilation under anesthesia in pigs. After asystole, animals were divided into 2 groups based on body positioning (supine or prone). All animals were subjected to 3 hours of warm ischemia. After the observation period, donor lungs were explanted and preserved at 4°C for 6 hours, followed by 6 hours of physiologic and biological lung assessment under normothermic ex vivo lung perfusion. Donor lungs from the prone group displayed significantly greater quality as reflected by better function during ex vivo lung perfusion, less edema formation, less cell death, and decreased inflammation compared with the supine group. A simple maneuver of donor prone positioning after cardiac arrest significantly improves lung graft preservation and function.
This study demonstrates the efficacy of donor prone positioning in preventing lung injury during periods of warm ischemia in a donation after cardiac death.
Robotic single-site cholecystectomy (RSSC) has been shown to be a safe alternative to the laparoscopic approach in selected patients. Patient exclusion criteria have prevented RSSC as a surgical ...option in many obese patients. This study reports the feasibility of performing RSSC in obese patients (body mass index BMI ≥ 30).
Between November 2012 and February 2014, a total of 200 patients underwent RSSC at our institution. All patients were offered the robotic procedure regardless of their BMI, age, previous surgery, and acuity of their disease with no exclusion criteria. All patients with BMI ≥ 30 were included in the study and were compared to nonobese patients for demographic characteristics, co-morbidities, and postoperative outcomes. Data were compared to RSSC performed in nonobese patients by the same surgeon, as well to published data for standard laparoscopic cholecystectomy (LC).
A total of 112 cholecystectomies were successfully performed with the robotic approach in patients with BMI ≥ 30 without conversion to open, laparoscopic, or multiport procedures. The mean BMI was 39.5 (range 30.1-62.3). Twenty-eight patients had a BMI ≥ 40 (25%), and 13 patients had a BMI ≥ 50 (11.6%). Fifty-two patients (46.4%) had a history of prior abdominal surgery. Most procedures were nonelective (78.6%) with patients presenting with acute symptoms. Pathology showed chronic cholecystitis and cholelithiasis in 79 patients (70.5%), acute cholecystitis in 26 patients (23.3%), cholelithiasis in 4 patients (3.5%), and gangrenous cholecystitis in 3 patients (2.7%). Total mean operative time was 69.8 (26) minutes for obese patients compared to 59.2 (19.7) minutes in the nonobese, which was statistically significant (P = .0012). After a mean follow-up of 6 months, there were no major complications recorded including bile leak, hematoma, or ductal injury. There was 1 umbilical (incisional) hernia (0.9%) reported, and zero wound infections. When comparing RSSC performed in obese patients, RSSC in nonobese patients, and published data for standard LC, we found no difference in operative time, with less conversion to open.
Robotic single-site cholecystectomy is a feasible option in the obese patient population with excellent short-term outcomes. Patients should not be excluded based on their high BMI although further study is needed to determine long-term outcomes.
Marijuana use has become more common since its legalization, as have reports of marijuana-associated spontaneous pneumomediastinum. Non-spontaneous causes such as esophageal perforation are often ...ruled out on presentation due to the severe consequences of untreated disease. Here we seek to characterize the presentation of marijuana-associated spontaneous pneumomediastinum and explore whether esophageal imaging is necessary in the setting of an often benign course and rising healthcare costs.
Retrospective review was performed for all 18-55 year old patients evaluated at a tertiary care hospital between 1/1/2008 and 12/31/2018 for pneumomediastinum. Iatrogenic and traumatic causes were excluded. Patients were divided into marijuana and control groups.
30 patients met criteria, with 13 patients in the marijuana group. The most common presenting symptoms were chest pain/discomfort and shortness of breath. Other symptoms included neck/throat pain, wheezing, and back pain. Emesis was more common in the control group but cough was equally prevalent. Leukocytosis was present in most patients. Four out of eight of computed tomography esophagarams in the control group showed a leak requiring intervention, while only one out of five in the marijuana group showed even a possible subtle extravasation of contrast but this patient ultimately was managed conservatively given the clinical picture. All standard esophagrams were negative. All marijuana patients were managed without intervention.
Marijuana-associated spontaneous pneumomediastinum appears to have a more benign clinical course compared to non-spontaneous pneumomediastinum. Esophageal imaging did not change management for any marijuana cases. Perhaps such imaging could be deferred if clinical presentation of pneumomediastinum in the setting of marijuana use is not suggestive of esophageal perforation. Further research into this area is certainly worth pursuing.
Background
There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the ...protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT.
Methods
Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized post-injury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment,
n
= 5) or recruitment maneuvers alone (control,
n
= 5) during ECMO.
Results
PaO
2
/FiO
2
after aspiration injury was 62.6 ± 8 mmHg and 60.9 ± 9.6 mmHg in the control and treatment group, respectively (
p
= 0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls.
Conclusions
A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.
Video-assisted thoracic surgery has considerably improved the care of the thoracic surgical patient. Patients are able to leave the hospital sooner and experience less pain with equal oncologic ...outcomes when compared with open surgery. Nonintubated thoracic surgery has more recently been applied in the management of both benign and malignant pleural effusions. This article provides the general thoracic surgeon a detailed description on how to manage pleural effusions using video-assisted thoracoscopic surgery in a nonintubated patient. Surgical techniques and pearls are also presented.
Abstract only
Pulmonary neuroepithelial bodies (NEBs) are airway chemoreceptors that express a membrane bound oxygen (O
2
) sensing molecular complex (NADPH oxidase) coupled to an O
2
sensitive K
+
...channel and are innervated by vagal afferents. A gap in the literature exists surrounding the development of myelinated nerves associated with NEBs during the perinatal period. Previous reports have documented NEBs associated with myelinated nerves at day 10 in the rat. Whether myelinated nerves innervating NEBs are observed throughout the NEB population or not has yet to be addressed. We used confocal microscopy with antibodies raised against synaptic vesicle protein (SV2) and myelin basic protein (MBP) to identify NEBs, their vagal afferents and the myelination of their nerve afferents, respectively, in the newborn rat lung. Lungs from newborn rat pups at postnatal day(s) 1 through 21 were studied. Double labeling with SV2 and MBP and analysis by confocal microscopy revealed NEBs negative for MBP prior to day 17 in the rat lung. The relatively large population of NEBs that are present in the perinatal period are not associated with myelinated nerve afferents. The appearance of myelinated nerve fibers in association with NEBs is not a frequent event. NEB numbers and activity is greatest during the prenatal period and decline post‐natally. Our results may support the idea that myelin is not required to support nerve activity originating from NEBs. (Supported by CIHR Grants MOP‐12742 and MPG‐15270)
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