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1.
J Vis Exp ; (180)2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35225271

RESUMO

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. However, lung transplantation is limited by a shortage of available donor organs. As such, there is high waitlist mortality. Ex situ lung perfusion (ESLP) has increased donor lung utilization rates in some centers by 15%-20%. ESLP has been applied as a method to assess and recondition marginal donor lungs and has demonstrated acceptable short- and long-term outcomes following transplantation of extended criteria donor (ECD) lungs. Large animal (in vivo) transplantation models are required to validate ongoing in vitro research findings. Anatomic and physiologic differences between humans and pigs pose significant technical and anesthetic challenges. An easily reproducible transplant model would permit the in vivo validation of current ESLP strategies and the preclinical evaluation of various interventions designed to improve donor lung function. This protocol describes a porcine model of orthotopic left lung allotransplantation. This includes anesthetic and surgical techniques, a customized surgical checklist, troubleshooting, modifications, and the benefits and limitations of the approach.


Assuntos
Transplante de Pulmão , Transplantes , Animais , Humanos , Pulmão/cirurgia , Transplante de Pulmão/métodos , Perfusão/métodos , Suínos , Doadores de Tecidos
2.
J Vis Exp ; (180)2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35225272

RESUMO

Lung transplantation (LTx) remains the standard of care for end-stage lung disease. A shortage of suitable donor organs and concerns over donor organ quality exacerbated by excessive geographic transportation distance and stringent donor organ acceptance criteria pose limitations to current LTx efforts. Ex situ lung perfusion (ESLP) is an innovative technology that has shown promise in attenuating these limitations. The physiologic ventilation and perfusion of the lungs outside of the inflammatory milieu of the donor body affords ESLP several advantages over traditional cold static preservation (CSP). There is evidence that negative pressure ventilation (NPV) ESLP is superior to positive pressure ventilation (PPV) ESLP, with PPV inducing more significant ventilator-induced lung injury, pro-inflammatory cytokine production, pulmonary edema, and bullae formation. The NPV advantage is perhaps due to the homogenous distribution of intrathoracic pressure across the entire lung surface. The clinical safety and feasibility of a custom NPV-ESLP device have been demonstrated in a recent clinical trial involving extender criteria donor (ECD) human lungs. Herein, the use of this custom device is described in a juvenile porcine model of normothermic NPV-ESLP over a 12 h duration, paying particular attention to management techniques. Pre-surgical preparation, including ESLP software initialization, priming, and de-airing of the ESLP circuit, and the addition of anti-thrombotic, anti-microbial, and anti-inflammatory agents, is specified. The intraoperative techniques of central line insertion, lung biopsy, exsanguination, blood collection, cardiectomy, and pneumonectomy are described. Furthermore, particular focus is paid to anesthetic considerations, with anesthesia induction, maintenance, and dynamic modifications outlined. The protocol also specifies the custom device's initialization, maintenance, and termination of perfusion and ventilation. Dynamic organ management techniques, including alterations in ventilation and metabolic parameters to optimize organ function, are thoroughly described. Finally, the physiological and metabolic assessment of lung function is characterized and depicted in the representative results.


Assuntos
Transplante de Pulmão , Edema Pulmonar , Animais , Humanos , Pulmão/patologia , Transplante de Pulmão/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Respiração Artificial , Suínos
3.
J Heart Lung Transplant ; 41(12): 1738-1750, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36137869

RESUMO

BACKGROUND: Evidence suggests that hearts that are perfused under ex-situ conditions lose normal coronary vasomotor tone and experience contractile failure over a few hours. We aimed to evaluate the effect of different coronary perfusion strategies during ex situ heart perfusion on cardiac function and coronary vascular tone. METHODS: Porcine hearts (n = 6 each group) were perfused in working mode for 6 hours with either constant aortic diastolic pressure (40 mmHg) or constant coronary flow rate (500 mL/min). Functional and metabolic parameters, cytokine profiles, cardiac and vascular injury, coronary artery function and oxidative stress were compared between groups. RESULTS: Constant coronary flow perfusion demonstrated better functional preservation and less edema formation (Cardiac index: flow control = 8.33 vs pressure control = 6.46 mL·min-1·g-1, p = 0.016; edema formation: 7.92% vs 19.80%, p < 0.0001). Pro-inflammatory cytokines, platelet activation as well as endothelial activation were lower in the flow control group. Similarly, less cardiac and endothelial injury was observed in the constant coronary flow group. Evaluation of coronary artery function showed there was loss of coronary autoregulation in both groups. Oxidative stress was induced in the coronary arteries and was relatively lower in the flow control group. CONCLUSIONS: A strategy of controlled coronary flow during ex situ heart perfusion provides superior functional preservation and less edema formation, together with less myocardial damage, leukocyte, platelet, endothelial activation, and oxidative stress. There was loss of coronary autoregulation and decrease of coronary vascular resistance during ESHP irrespective of coronary flow control strategy. Inflammation and oxidative stress state in the coronary vasculature may play a role.


Assuntos
Vasos Coronários , Transplante de Coração , Suínos , Animais , Perfusão , Coração/fisiologia , Miocárdio/metabolismo
4.
CJC Open ; 4(11): 979-988, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36444372

RESUMO

Background: This study reports on the main criteria used by Canadian cardiac surgery residency program committees (RPCs) to select applicants and the perceptions of Canadian medical students interested in cardiac surgery. Methods: A 50-question online survey was sent to all 12 Canadian cardiac surgery RPCs. A similar 52-question online survey targeted at Canadian medical students interested in applying to cardiac surgery residency programs was distributed. Data from both surveys were analyzed using descriptive statistics. Results: A total of 62% of all cardiac surgery RPC members (66 of 106) participated, including committee members from all 12 programs (range: 1-12 members per program; 9%-100% response rate per program) and 67% of program directors (8 of 12). Forty-one Canadian medical students (22 pre-clerks [54%], 2 MD/PhD students [5%], and 17 clinical clerks [41%]) participated. Committee members considered the following criteria to be most important when selecting candidates: on-service clinical performance, the interview, quality of reference letters from cardiac surgeons, and completing a rotation at the target program's institution. In contrast, the following criteria relating to the candidate were considered to be less important: wanting to practice in the city or province of training, having a connection to the program location, and personally knowing committee members. Medical students' perceptions were concordant regarding what factors are the most important but they overestimated the influence of non-clinical factors and research productivity in increasing their competitiveness. Conclusion: Canadian cardiac surgery residency programs seek applicants who demonstrate clinical excellence, as assessed by surgical rotations and reference letters from colleagues, and strong interview performance.


Contexte: Cette étude fait état des principaux critères utilisés par les comités des programmes de résidence (CPR) canadiens en chirurgie cardiaque pour sélectionner les candidats, ainsi que des perceptions des étudiants en médecine canadiens qui s'intéressent à la chirurgie cardiaque. Méthodologie: Un sondage en ligne comptant 50 questions a été envoyé aux 12 CPR canadiens en chirurgie cardiaque. Un sondage en ligne semblable (comptant 52 questions) a été distribué aux étudiants en médecine qui souhaitaient soumettre leur candidature à un programme de résidence en chirurgie cardiaque au Canada. Les données des deux sondages ont été analysées à l'aide de statistiques descriptives. Résultats: Au total, 62 % des membres de CPR en chirurgie cardiaque (66 sur 106) ont répondu au sondage, y compris des membres des comités des 12 programmes (plage : 1 à 12 membres par programme; taux de réponse de 9 à 100 % par programme) et 67 % des directeurs de programme (8 sur 12). Au total, 41 étudiants en médecine canadiens (22 en préexternat [54 %], 2 étudiants au M.D./Ph. D. [5 %] et 17 stagiaires en formation clinique [41 %]) ont répondu au sondage. Les membres du comité ont considéré les critères suivants comme étant les plus importants dans le choix de candidats : le rendement clinique en service, l'entrevue, la qualité des lettres de recommandation de chirurgiens cardiaques et la réalisation d'un stage dans l'établissement associé au programme. En revanche, les critères suivants étaient considérés comme moins importants : le désir de pratiquer dans la ville ou la province de formation, un lien avec le lieu du programme, et la connaissance personnelle de membres du co-mité. Les perceptions des étudiants en médecine concordaient quant aux facteurs les plus importants, mais les étudiants surestimaient l'influence de facteurs non cliniques et de la productivité en recherche dans l'aspect concurrentiel de leur candidature. Conclusion: Les programmes de résidence canadiens en chirurgie cardiaque recherchent des candidats forts d'une excellence clinique, évaluée par les stages en chirurgie et les lettres de recommandation de collègues, et offrant une bonne performance en entrevue.

5.
Cells ; 10(6)2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200413

RESUMO

Lung transplantation (LTx) is the gold standard treatment for end-stage lung disease; however, waitlist mortality remains high due to a shortage of suitable donor lungs. Organ quality can be compromised by lung ischemic reperfusion injury (LIRI). LIRI causes pulmonary endothelial inflammation and may lead to primary graft dysfunction (PGD). PGD is a significant cause of morbidity and mortality post-LTx. Research into preservation strategies that decrease the risk of LIRI and PGD is needed, and ex-situ lung perfusion (ESLP) is the foremost technological advancement in this field. This review addresses three major topics in the field of LTx: first, we review the clinical manifestation of LIRI post-LTx; second, we discuss the pathophysiology of LIRI that leads to pulmonary endothelial inflammation and PGD; and third, we present the role of ESLP as a therapeutic vehicle to mitigate this physiologic insult, increase the rates of donor organ utilization, and improve patient outcomes.


Assuntos
Endotélio Vascular/metabolismo , Transplante de Pulmão , Pulmão/metabolismo , Disfunção Primária do Enxerto/prevenção & controle , Endotélio Vascular/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Pulmão/patologia , Perfusão , Disfunção Primária do Enxerto/metabolismo , Disfunção Primária do Enxerto/patologia
6.
Ann Thorac Surg ; 109(1): e37-e39, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31228410

RESUMO

Aortico-left ventricular tunnel is a rare congenital anomaly requiring surgical repair early in childhood. After corrective surgery, such patients are at risk of developing aortic insufficiency and aortic root dilatation. Herein, we describe a valve-sparing aortic root replacement 3 decades after the repair of aortico-left ventricular tunnel.


Assuntos
Anormalidades Múltiplas/cirurgia , Aorta/anormalidades , Aorta/cirurgia , Valva Aórtica/cirurgia , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Complicações Pós-Operatórias/cirurgia , Adulto , Procedimentos Cirúrgicos Cardíacos/métodos , Humanos , Masculino , Tratamentos com Preservação do Órgão/métodos , Fatores de Tempo , Procedimentos Cirúrgicos Vasculares/métodos
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