Pedro Reck dos Santos1, Ilker Iskender1, Tiago Machuca2, David Hwang2, Marc dePerrot1, Mingyao Liu1, Shaf Keshavjee1, Thomas K Waddell1, Marcelo Cypel3. 1. Latner Thoracic Surgery Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 2. Latner Thoracic Surgery Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada. 3. Latner Thoracic Surgery Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: marcelo.cypel@uhn.ca.
Abstract
OBJECTIVES: In vivo lung perfusion (IVLP) is an emergent strategy to treat lung metastases because it allows localized delivery of chemotherapy with minimal systemic exposure. Previously, short-term (± 30 minutes) IVLP resulted in variable efficacy and significant lung toxicity. We hypothesize that a modified IVLP strategy derived from an ex vivo lung perfusion technique could minimize lung injury. Our objective was to demonstrate the feasibility and safety of a modified prolonged (4 hours) IVLP. METHODS: Six Yorkshire pigs were used for the experiments. A thoracotomy was performed, the left pulmonary artery and pulmonary veins were cannulated, and the left lung was isolated in situ. IVLP was performed at normothermia for 4 hours using Steen Solution (XVIVO Perfusion, Göteburg, Sweden) as perfusate. The flow rate was 16% of estimated cardiac output and left atrial pressure was maintained between 3 and 5 mm Hg. Perfusate was deoxygenated and supplied with CO2 to physiologic levels before entering the lungs. A protective mode of ventilation was used. After IVLP, the left lung was allowed to reperfuse for additional 4 hours. Airway dynamics, gas exchange, and pulmonary vascular resistance were used to assess left lung physiology. Histologic signs of lung injury were assessed before and after IVLP, and 4 hours after reperfusion. RESULTS: Lung function parameters were stable throughout the 4-hour IVLP and during reperfusion. No significant histologic evidence of acute lung injury was observed. CONCLUSIONS: Four hours of IVLP is feasible without adding significant lung injury. Prolonged perfusion time and a protective protocol might provide safer and more efficacious treatment of pulmonary metastases.
OBJECTIVES: In vivo lung perfusion (IVLP) is an emergent strategy to treat lung metastases because it allows localized delivery of chemotherapy with minimal systemic exposure. Previously, short-term (± 30 minutes) IVLP resulted in variable efficacy and significant lung toxicity. We hypothesize that a modified IVLP strategy derived from an ex vivo lung perfusion technique could minimize lung injury. Our objective was to demonstrate the feasibility and safety of a modified prolonged (4 hours) IVLP. METHODS: Six Yorkshire pigs were used for the experiments. A thoracotomy was performed, the left pulmonary artery and pulmonary veins were cannulated, and the left lung was isolated in situ. IVLP was performed at normothermia for 4 hours using Steen Solution (XVIVO Perfusion, Göteburg, Sweden) as perfusate. The flow rate was 16% of estimated cardiac output and left atrial pressure was maintained between 3 and 5 mm Hg. Perfusate was deoxygenated and supplied with CO2 to physiologic levels before entering the lungs. A protective mode of ventilation was used. After IVLP, the left lung was allowed to reperfuse for additional 4 hours. Airway dynamics, gas exchange, and pulmonary vascular resistance were used to assess left lung physiology. Histologic signs of lung injury were assessed before and after IVLP, and 4 hours after reperfusion. RESULTS: Lung function parameters were stable throughout the 4-hour IVLP and during reperfusion. No significant histologic evidence of acute lung injury was observed. CONCLUSIONS: Four hours of IVLP is feasible without adding significant lung injury. Prolonged perfusion time and a protective protocol might provide safer and more efficacious treatment of pulmonary metastases.
Authors: J Hunter Mehaffey; Eric J Charles; Sarah Schubert; Morgan Salmon; Ashish K Sharma; Dustin Money; Mark H Stoler; Victor E Laubach; Curtis G Tribble; Mark E Roeser; Irving L Kron Journal: J Thorac Cardiovasc Surg Date: 2017-09-14 Impact factor: 5.209
Authors: Matthew R Byler; Nathan S Haywood; Dustin T Money; Aimee Zhang; Jared P Beller; Eric J Charles; William Z Chancellor; Huy Q Ta; Mark H Stoler; J Hunter Mehaffey; Victor E Laubach; Irving L Kron; Mark E Roeser Journal: Semin Thorac Cardiovasc Surg Date: 2021-03-11
Authors: Barbara Bojko; Nikita Looby; Mariola Olkowicz; Anna Roszkowska; Bogumiła Kupcewicz; Pedro Reck Dos Santos; Khaled Ramadan; Shaf Keshavjee; Thomas K Waddell; German Gómez-Ríos; Marcos Tascon; Krzysztof Goryński; Marcelo Cypel; Janusz Pawliszyn Journal: J Pharm Anal Date: 2020-09-02
Authors: Nathan Haywood; Matthew R Byler; Aimee Zhang; Mark E Roeser; Irving L Kron; Victor E Laubach Journal: Int J Mol Sci Date: 2020-09-17 Impact factor: 5.923