Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: I. Influence of perfusion pressure and hyperthermia on functional and morphological lung integrity.

OBJECTIVE

Despite favorable experimental results and an encouraging early experience in humans, isolated lung perfusion (ILP) for treatment of metastases is still not established clinically. The complexity of the procedure as well as poor knowledge regarding the technical necessities of lung perfusion represents major limitations.

METHODS

In this novel in vivo pig model, ILP of the left lung was performed for 40 min followed by the exclusion of the right lung. Survival and all monitored parameters of hemodynamics, ventilation and gas exchange were exclusively dependent on the previously perfused left lung for the 6-h reperfusion period. Furthermore, histological examination was assessed. In the first protocol influence of different perfusion pressures (PP) on the native lung tissue was investigated (LPG, n=6, PP<25 mmHg; HPG, n = 8, PP> or =25 mmHg). In the second protocol the influence of normothermic (T-38; n=5; t=38 degrees C), mild (T-40; n=5; t=40 degrees C) and moderate hyperthermic (T-41.5; n=5; t=41.5 degrees C) perfusion temperature was evaluated. Results were compared to those of a sham-operated control group (SG, n=5).

RESULTS

ILP led to a slight deterioration of all functional as well as histological parameters in all groups. HPG resulted in impairment regarding all monitored parameters compared to LPG and SG. Significant differences between HPG and SG were found for cardiac index (P=0.026) and pulmonary vascular resistance index (PVRI, P=0.026). Histological scoring revealed significantly higher grade of lung injury for HPG animals (P=0.001). Functional parameters did not differ between normothermic and hyperthermic perfusion groups. However, animals of the T-38 group demonstrated significantly increased PVRI (P=0.004). Histological examination revealed significantly higher scores of acute lung injury for all perfusion groups compared to the Sham group (P<0.001).

CONCLUSIONS

The results of this novel large animal model represent the first available demonstration that increased PP in a setting of ILP will result in deleterious effects on lung function and morphology. However, mild to moderate hyperthermia is well tolerated by the native lung tissue.