Modified In Vivo Lung Perfusion for Local Chemotherapy: A Preclinical Study With Doxorubicin Pedro Reck dos Santos, MD, MS, Jin Sakamoto, MD, Manyin.

Slides:

Advertisements

Similar presentations

Marcelo Cypel, MD, MSc, Jonathan C

Advertisements

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome After Pneumonectomy Jeremie Reeb, MD, MS, Anne Olland, MD, PhD, Julien Pottecher,

Mary E. Huerter, MD, MA, Ashish K

Annexin V homodimer protects against ischemia reperfusion–induced acute lung injury in lung transplantation Kohei Hashimoto, MD, Hyunhee Kim, MSc, Hisashi.

Off-Pump Surgery for Multiple Coronary Artery Fistulas With Aneurysm

Duodenal Reflux Leads to Down Regulation of DNA Mismatch Repair Pathway in an Animal Model of Esophageal Cancer Pramod Bonde, MD, MS, Daqing Gao, PhD,

Keiji Ohata, MD, Toyofumi F

Extracorporeal lung membrane provides better lung protection than conventional treatment for severe postpneumonectomy noncardiogenic acute respiratory.

Carbon monoxide reduces pulmonary ischemia–reperfusion injury in miniature swine Hisashi Sahara, MD, Akira Shimizu, MD, PhD, Kentaro Setoyama, DVM, PhD,

Invasive Mediastinal Staging Guideline Concordance

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non–heart-beating donors Boming Dong, MD, PhD, Paul.

Amit Mathur, MD, Maher Baz, MD, E

Ex Vivo Evaluation of Nonacceptable Donor Lungs

Adenosine A2A receptor activation on CD4+ T lymphocytes and neutrophils attenuates lung ischemia–reperfusion injury Ashish K. Sharma, MBBS, Victor E.

J. Hunter Mehaffey, MD, Eric J. Charles, MD, Ashish K

Free-radical scavenger edaravone inhibits both formation and development of abdominal aortic aneurysm in rats Keisuke Morimoto, MD, Tomomi Hasegawa,

Ex Vivo Bilateral Pulmonary Embolectomy for Donor Lungs Prior to Transplantation Mohammad Shihata, MD, Nitin Ghorpade, MD, Dale Lien, MD, Dennis Modry,

Long-Term Outcome After Resection of Non-Small Cell Lung Cancer Invading the Thoracic Inlet Stéphane Collaud, MD, MS, Tiago Machuca, MD, PhD, Olaf Mercier,

Enhanced In Vivo Function of Bioartificial Lungs in Rats

Improved Myocardial Perfusion and Thickening After Off-Pump Revascularization: 5- Year Follow-Up Chang Young Kim, MD, Ho Young Hwang, MD, Jin Chul Paeng,

Nathalie Roy, MD, Ingeborg Friehs, MD, Douglas B

Ex vivo rehabilitation of non–heart-beating donor lungs in preclinical porcine model: Delayed perfusion results in superior lung function Daniel P. Mulloy,

Sevoflurane Attenuates Ischemia-Reperfusion Injury in a Rat Lung Transplantation Model Akihiro Ohsumi, MD, Katherine Marseu, MD, Peter Slinger, MD, Karen.

Inhaled nitric oxide attenuates apoptosis in ischemia-reperfusion injury of the rabbit lung Hideki Yamashita, MD, Shinji Akamine, MD, Yorihisa Sumida,

Experimental lung preservation with perfadex: effect of the no-donor nitroglycerin on postischemic outcome Thorsten Wittwer, MD, PhD, Johannes M Albes,

Eric J. Charles, MD, Mary E. Huerter, MD, MA, Cynthia E

Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death Cynthia E. Wagner,

Sivelestat Attenuates Lung Injury in Surgery for Congenital Heart Disease With Pulmonary Hypertension Norikazu Nomura, MD, PhD, Miki Asano, MD, PhD,

Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation Ari O Halldorsson, MD, Michael Kronon, MD, Bradley S Allen, MD, Shaikh.

Ex Vivo Evaluation of Human Lungs for Transplant Suitability

Surfactant Improves Graft Function After Gastric Acid–Induced Lung Damage in Lung Transplantation Ilhan Inci, MD, Sven Hillinger, MD, Stephan Arni, PhD,

Total Liquid Ventilation Reduces Lung Injury in Piglets After Cardiopulmonary Bypass Lijun Jiang, MD, Qiang Wang, MD, Yinglong Liu, MD, Ming Du, MD, Xiangdong.

Low-Dose Nitric Oxide Inhalation During Initial Reperfusion Enhances Rat Lung Graft Function Moninder S Bhabra, FRCS, David N Hopkinson, MD, Trudi E.

Sarah M. Brant, MD, Michael L. Cobert, PhD, LaShondra M

Nebulized nitrite protects rat lung grafts from ischemia reperfusion injury Toshihiro Okamoto, MD, PhD, Xiaoying Tang, MS, Allison Janocha, BS, Caral.

Surgical Resection of a Giant Coronary Aneurysm

Itaru Nagahiro, MD, Tyler White, PhD, Motoki Yano, MD, Carlos H. R

William T. Mahle, MD, Emilia Matthews, MS, Kirk R. Kanter, MD, Brian E

Carbon monoxide–saturated preservation solution protects lung grafts from ischemia– reperfusion injury Junichi Kohmoto, MD, Atsunori Nakao, MD, Ryujiro.

Volume 67, Issue 6, Pages (June 2005)

Abbas Emaminia, MD, Damien J

Erin M. Schumer, MS, MD, Keith A. Zoeller, MEng, Paul L

The protective effect of prone lung position on ischemia–reperfusion injury and lung function in an ex vivo porcine lung model Hiromichi Niikawa, MD,

Inhibition of MicroRNA-204 Conducts Neuroprotection Against Spinal Cord Ischemia Lihui Yan, MD, Enyi Shi, MD, PhD, Xiaojing Jiang, MD, PhD, Jiang Shi,

Use of Single-Cannula Venous-Venous Extracorporeal Life Support in the Management of Life-Threatening Airway Obstruction Michael Ko, MD, Pedro R. dos.

Changes in P-Selectin Expression on Cardiac Microvessels in Blood-Perfused Rat Hearts Subjected to Ischemia-Reperfusion Andrew O. Chukwuemeka, FRCS,

Bilobectomy for Lung Cancer: Analysis of Indications, Postoperative Results, and Long- Term Outcomes Domenico Galetta, MD, PhD, Piergiorgio Solli, MD,

Satona Tanaka, MD, Toyofumi F

Use of Amiodarone After Major Lung Resection

Robert J. Cerfolio, MD, Thomas C. Matthews, BS

Denis W. Harkin, MD, Aires A. B

Abel Gómez-Caro, MD, Pedro Arguis, MD The Annals of Thoracic Surgery

Anomalous Origin of Left Pulmonary Artery From Left Subclavian Artery

PaO2/FiO2 Deterioration During Stable Extracorporeal Membrane Oxygenation Associates With Protracted Recovery and Increased Mortality in Severe Acute.

Hidetoshi Inokawa, MD, PhD, Mayura Sevala, PhD, William K

Combining Cerebral Perfusion With Retrograde Inferior Vena Caval Perfusion for Aortic Arch Surgery Jing Lin, MD, Jiyue Xiong, MS, Ming Luo, MS, Zhaoxia.

High Risk for Thoracotomy but not Thoracoscopic Lobectomy

CD4+ T lymphocytes mediate acute pulmonary ischemia–reperfusion injury

Sarah C. Huen, MD, Chirag R. Parikh, MD, PhD

Extensive Invasion of the Left Atrium by Lung Cancer

Nonoperative Damage Control: The Use of Extracorporeal Membrane Oxygenation in Traumatic Bronchial Avulsion as a Bridge to Definitive Operation Nathan.

The Acute Effects of Transthoracic Cryoablation on Normal Lung Evaluated in a Porcine Model Yotaro Izumi, MD, PhD, Takahiko Oyama, MD, Eiji Ikeda, MD,

Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation Hideki Itano, MD, Motoi Aoe, MD, Shingo Ichiba, MD, Motohiro.

Ronald A. Bronicki, MD, Carl L. Backer, MD, Harris P

Pulmonary Artery Tumor Embolism in a Patient With Previous Fibroblastic Osteosarcoma Silviu Buderi, MD, MS, Thomas Theologou, MD, MS, John Gosney, MD,

Donor Treatment With the Lazeroid U74389G Reduces Ischemia–Reperfusion Injury in a Rat Lung Transplant Model Bernard Hausen, Peter Mueller, Marcus Bahra,

José L. Navia, MD, Fernando A. Atik, MD, Erik A

The Impact of New Technology on Cardiothoracic Surgical Practice

Marcelo Cypel, MD, MSc, Jonathan C

Harvey Edward Garrett, MD, Bradley A. Wolf, MD

Presentation transcript:

Modified In Vivo Lung Perfusion for Local Chemotherapy: A Preclinical Study With Doxorubicin Pedro Reck dos Santos, MD, MS, Jin Sakamoto, MD, Manyin Chen, MD, Virginia Linacre, MD, Chantel Arce, BS, Mingyao Liu, MD, MS, Thomas K. Waddell, MD, PhD, Shaf Keshavjee, MD, MS, Marcelo Cypel, MD, MS The Annals of Thoracic Surgery Volume 101, Issue 6, Pages 2132-2140 (June 2016) DOI: 10.1016/j.athoracsur.2015.12.043 Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 In vivo lung perfusion (IVLP) system. Perfusate enters left lung through left pulmonary artery (1) and is drained by upper (2) and lower left pulmonary veins (3). After leaving left lung (4), perfusate is collected in hard-shell reservoir (5) and then directed to centrifugal pump (6), which drives flow to membrane gas exchanger, where combination of gas (oxygen, 6%; carbon dioxide, 8%; nitrogen, 86%) is added to deoxygenate perfusate and provides CO2 for inflow. Perfusate then passes leukocyte filter (8) and returns to left pulmonary artery (9). Temperature of perfusate is controlled by heat exchanger connected to gas exchanger. Standard intensive care unit type of ventilator provides ventilation to both lungs. The Annals of Thoracic Surgery 2016 101, 2132-2140DOI: (10.1016/j.athoracsur.2015.12.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Lung function and histologic assessment in in vivo lung perfusion (IVLP) with 75 mg/m2 of doxorubicin (n = 5). (A) Stable oxygenation, airway dynamics, and pulmonary artery pressure (PAP) were observed during IVLP and after 4 hours of reperfusion. No statistical difference was observed in histologic acute lung injury score between (B) before IVLP, (C) after IVLP, and (D) after reperfusion. (Cdyn = dynamic compliance; PAWP = peak airway pressure.) The Annals of Thoracic Surgery 2016 101, 2132-2140DOI: (10.1016/j.athoracsur.2015.12.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Lung function and histologic assessment in in vivo lung perfusion (IVLP) with 75 mg/m2 of doxorubicin (Dox) + 6 g/m2 of ifosfamide (Ifos) (n = 3). (A) Stable oxygenation, airway dynamics, and pulmonary artery pressure (PAP) were observed during IVLP and after 4 hours of reperfusion. No statistical difference was observed in histologic acute lung injury score between (B) before IVLP, (C) after IVLP, and (D) after reperfusion. (Cdyn = dynamic compliance; PawP = peak airway pressure; P/F = Pao2/Fio2.) The Annals of Thoracic Surgery 2016 101, 2132-2140DOI: (10.1016/j.athoracsur.2015.12.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Lung function of 2 animals submitted to in vivo lung perfusion (IVLP) with doxorubicin (Dox) 150 mg/m2 (pig 1, purple line; pig 2, green line). (A) Stable airway dynamics and pulmonary artery pressure (PAP) were observed during IVLP and after 4 hours of reperfusion. A drop in oxygenation levels characterized injury during reperfusion in both animals. In comparison with (B) before IVLP, histologic samples collected at the end of IVLP showed (C) air space hemorrhage, and samples collected at the end of reperfusion showed (D) more air space hemorrhage and white blood cell infiltration. (Cdyn = dynamic compliance; PAWP = peak airway pressure; P/F = Pao2/Fio2.) The Annals of Thoracic Surgery 2016 101, 2132-2140DOI: (10.1016/j.athoracsur.2015.12.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Tissue and perfusate doxorubicin (Dox) levels measured in experiments with Dox 75 mg/m2 (n = 8). (A) Tissue levels of Dox were examined in 3 different areas of the lung—upper, middle, and lower—at the end of reperfusion. No statistically significant difference was found at end of reperfusion across 3 areas (n = 8; p > 0.26). (B) Perfusate levels were also assessed 10 minutes after administration of chemotherapy, followed by hourly assessments. Peak perfusate levels of Dox occurred at 1 hour of IVLP. The Annals of Thoracic Surgery 2016 101, 2132-2140DOI: (10.1016/j.athoracsur.2015.12.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 6 Inflammatory cytokine profile in lung tissue. We measured 4 inflammatory cytokines in lung tissue before perfusion and at end of procedure (after 4 hours of in vivo lung perfusion [IVLP] + 4 hours of reperfusion), according to the dose of chemotherapy (doxorubicin [Dox] 75 mg/m2, Dox 75 mg/m2 + ifosfamide [Ifos] 6g/m2, and Dox 150 mg/m2). IVLP with Dox 150 mg/m2 resulted in significant increase in interleukin (IL)-8 levels compared with samples before perfusion as well as compared with other groups analyzed (p < 0.0001). Levels of IL-6, IL-1β, and tumor necrosis factor-alpha (TNFα) were not statistically significant. The Annals of Thoracic Surgery 2016 101, 2132-2140DOI: (10.1016/j.athoracsur.2015.12.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

Fig 7 Cell death during reperfusion. Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining was performed to identify apoptotic cells (red spots) in samples collected after 4 hours of in vivo lung perfusion (IVLP) + 4 hours of reperfusion. Quantification of TUNEL- positive cells was evaluated and demonstrated significantly more apoptotic cells in doxorubicin (Dox) 150 mg/m2 group compared with other groups; p = 0.0014). The Annals of Thoracic Surgery 2016 101, 2132-2140DOI: (10.1016/j.athoracsur.2015.12.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions