Comparison of Pulsatile and Nonpulsatile Perfusion of the Lung in an Extracorporeal Large Animal Model

Abstract

Objective: Extracorporeal lung-perfusion models are widely used to evaluate pulmonary preservation techniques and reperfusion injury. However, these models mainly depend on nonpulsatile flow, which is not physiological and can subsequently lead to pulmonary edema. Observation in a standardized setting and reliability of functional and structural data assessment are therefore limited. To overcome these limitations we developed a new extracorporeal large animal lung perfusion model utilizing pulsatile flow to perfuse the pulmonary vasculature. Methods: Lungs of juvenile domestic pigs were in situ preserved with 2 liters Perfadex^® and stored for 3 h at 10°C. Thereafter, reperfusion of the lung was performed in an extracorporeal blood perfusion circuit employing either a modified roller pump with pulsatile module (300 ml/min; pulsation rate 90/min) or a standardized roller pump with continuous flow (30 ml/min). Ventilation was performed with physiologic room air (350 ml; 16/min) for 1 h. Pulsatile and nonpulsatile perfusion was performed in 2 groups (group NP: nonpulsatile; group P: pulsatile flow, n = 7) during reperfusion. Peak inspiratory pressure (PIP), mean pulmonary artery pressure (PAP), and oxygenation capacity (ΔPO₂) were continuously measured. For control of the effectiveness of the pulsatile perfusion pressure waveforms were obtained directly from the native pulmonary artery of both groups. Malondialdehyde (MDA) as a parameter for lipid peroxidation and endothelial cell damage was assessed at 10, 30 and 50 min reperfusion. At the end of the study, pulmonary water content was assessed by means of wet-to-dry ratio (W/D ratio). The tissue was further processed for microscopic analysis. Results: PIP increased significantly in both groups during reperfusion. Mean PAP in both groups increased to 60 mm Hg after 20 min followed by a decrease after 60 min to 40 mm Hg. Pressure waveforms of the pulmonary artery showed sufficient pulsatility in the pulmonary vasculature with a systolic/diastolic pressure difference of 15 mm Hg whereas the pressure difference was 3–5 mm Hg in the nonpulsatile group. ΔPO₂ was stable in groups NP and P during reperfusion (30 min: NP: 66.4 (62.2–88) mm Hg; P: 74.8 (65–81.7) mm Hg) without any statistically significant differences between the groups. MDA in group NP decreased over the reperfusion period from 6.2 (3.3–6.3) µM at 10 min to 5.2 (3.2–6.1) µM at 50 min, whereas in group P the level increased and was significantly higher after 50 min reperfusion compared to group NP [6.6 (6.1–9.2) µM at 50 min; p = 0.016]. W/D ratio was 6.7 (6.3–7.0) in group NP and 6.8 (6.3–7.6) in group P. Light microscopy evaluation showed no differences between both groups regarding severity of intra-alveolar and interstitial edema and numbers of intra-alveolar, intracapillary and interstitial granulocytes. Conclusion: Although effective pulsatile perfusion of the pulmonary vasculature was achieved by means of a modified roller pump, this measure obviously did not improve fu...

Normothermic Ex Vivo Perfusion Prevents Lung Injury Compared to Extended Cold Preservation for Transplantation

“…(15)(16)(17)(18)(19) (20)(21)(22). However, past attempts at prolonged machine preservation have largely failed due to inability to maintain the integrity and normal barrier functions of the vasculature and epithelial beds leading to progressive deterioration in vascular flow and the concurrent development of edema (23)(24)(25). We have recently demonstrated successful application of an acellular EVLP technique in maintaining lung viability ex vivo for an extended period of time (26).…”

Technique for Prolonged Normothermic Ex Vivo Lung Perfusion

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Lung ischaemia–reperfusion injury in a canine model: dual-energy CT findings with pathophysiological correlation

“…Experimental animal models are intrinsically limited; although, analogous experiments would be very difficult to perform clinically. In terms of model selection, both canines and pigs tolerate such procedures well; however, the structure of lung tissues, distribution of pulmonary segments and vasculature morphology of canines are more similar to humans, 27 and canines are more cost effective. Compared with rats and rabbits, the vasculature of canines and pigs are thicker, which is better suited for interventional procedures.…”