PhD Scientific Days 2021

TT_II_L: Theoretical and Translational Medicine II. Lectures

Experimental isolated lung perfusion model’s implication for physiological and pharmacological studies

Text of the abstract

Introduction: The Development of the isolated lung perfusion technique started in the early 70s using canine animal models. Amajor clinical breakthrough came in 2001, when clinicians were able to assess human lung function from non-heart-beating donors and had the first successful lung transplantation using ex-vivo lung perfusion (EVLP). Nowadays EVLP is routinely used in many lung transplantation centers to measure marginal donor functions.
Aims: Most of the experimental EVLP studies rely on rejected donors or animal organs. Our aim is to investigate the applicability of EVLP on surgically resected cancerous human lobe or lung for pharmacological and physiological studies.
Methods: Surgery is performed according to our clinical practice: either via open surgery (anterolateral thoracotomy) or minimally invasive approach. Non-small cell lung cancers are the most frequent tumor type, which is routinely operated at, unlike small cell lung cancer, which is most likely considered inoperable at the time of diagnosis. The resected lobe or lung is immediately submerged in cold saline. It is transported to another operating room where we open all ligated or stapled vessels to evacuate blood and possible thrombi. It is carefully inspected for any iatrogenic damages. If it’s considered suitable for the experiment, all bronchial and vascular stumps are anastomosed into a circuit with an ECMO machine and a ventilator. ECMO machine is used for circulation and deoxygenation of the perfusatein order to mimic the body’s oxygen consumption. We are able to measure physiological parameters in the lobe or lung such as pulmonary artery and vein pO2 and pCO2, pH, glucose consumption, lactate production, ventilation parameters. If the pH of the perfusate decreases under 7 or edema formation limits gas exchange in the organ, we terminate the experiment. The ideal lobe or lung can be perfused for up to 4 hours.
Results and conclusion: This is the first time in Hungary that a human EVLP-like experiment is conducted. In this setting, we are able to administer inhaled or soluble drugs to investigate their intratumoral and intrapulmonary distribution in near-physiological conditions. These experiments will pave the way for surgeons to use EVLP in the Hungarian Lung Transplantation Program.
Funding: Supported by Semmelweis 250+ Kiválósági PhD Ösztöndíj (EFOP-3.6.3-VEKOP-16-2017-00009)

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine