A Study on Pulmonary Toxic Effect of High-Dose Cisplatin Administered by Isolated Lung Perfusion in Dogs / 대한흉부외과학회지

ABSTRACT

BACKGROUND: Isolated lung perfusion (ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. MATERIAL AND METHOD: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme (ACE), tumor necrosis factor-alpha (TNF-alpha), and concentration of serum lactate dehydrogenase (LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. RESULT: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1+/-6.3, 44.6+/-9.3, 46.7+/-9.5, 50.8+/-9.1, 46.1+/-4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4+/-12.6, 39.0+/-8.6, 42.3+/-15.9, 50.0+/-2.6, 53.8+/-8.3 and 55.5+/-12.3, 47.0+/-6.3, 45.1+/-6.9, 74.8+/-19.5, 60.2+/-12.0 U/L, respectively. Serum TNF-alpha activities in each group before and after ILP were 5.0+/-1.5 / 7.7+/-2.2 / 6.6+/-2.5 / 4.3+/-1.3 / 5.2+/-1.1 (control), 8.7+/-1.6 / 9.9+/-2.2 / 7.9+/-1.5 / 6.3+/-2.2 / 7.4+/-2.4 (cisplatin 2.5 mg/Kg), and 6.9+/-0.7 / 8.9+/-3.4 / 7.9+/-4.0 / 3.3+/-0.9 / 5.8+/-1.3 pg/ml (cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L (cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-alpha, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. CONCLUSION: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.