# Efficacy of Iopamidol for Sealing an Injured Thoracic Duct: Pilot Experiments in a Large Animal
## 4 Discussion
This indicated that isopamidol was retained at the injured site, which led to the obstruction of the thoracic duct. The pathological findings revealed that isopamidol unpredictably filled and completely blocked the thoracic ducts. Although this is not observed in clinical practice, further studies are needed to determine whether the lumen of the thoracic duct is obstructed by isopamidol over time, as it is water-soluble. If the damaged area is sealed without leakage and the thoracic duct is communicated, isopamidol may be a better treatment option than TDE. The FDA report on isopamidol [18] states that \"Opacification of the calves and pelves in patients with normal renal function becomes apparent within 1 to 3 min, with optimum contrast occurring between 5 and 15 min.\" Therefore, after the first injection of the contrast medium, we considered that it would take at least 5 min to avoid interference of the re-injected isopamidol with the previous injection. We decided to observe leakage at 5 and 10 min. Furthermore, as there may be re-leakage even if it was initially prevented, we decided to check leakage again at 30 min. When planning the experiment, we did not expect that isopamidol would prevent injury by filling the amorphous proteinaceous material within the thoracic duct, as observed in the histological analysis (Figure 4). Additionally, the lymphangiography findings presented in Figure 1F,H show that the damaged part (arrow) of the thoracic duct does not show contrast, as if an apple was hollowed inward. This further validates that some material filled the thoracic duct. The use of isopamidol as a clinical therapeutic agent for lymphangiography has not been reported; our preliminary animal experiments showed that isopamidol may be an alternative therapeutic agent for treating chylous leakage. Additional animal studies and clinical trials to demonstrate the therapeutic effect of isopamidol on chylothorax may reduce or eliminate the incidence of systemic embolism induced by lipiodol. In addition, coil embolization may be avoided, which could reduce the treatment cost to and economic burden on the patient. There were some limitations associated with this study because it was a pilot study to determine whether isopamidol, similar to lipiodol, can seal an injured thoracic duct. Firstly, there was a limitation in statistical analysis because the sample size was small and there was no sham group (pigs with thoracic duct injury and not treated with lipiodol or isopamidol) for comparison. Secondly, although the anatomical structure of the porcine lymphatic system is similar to that of humans, further research is needed to apply these findings directly to humans. In conclusion, we showed the potential of isopamidol as a new therapeutic agent for chylous leakage in the present study. If thoracic duct embolization fails or if there is a risk of systemic embolizationfollowing lipidod injection, ipamidol injected via the thoracic duct may be a safe treatment that is worth further investigation. Conceptualization, H.Y.A., S.S., U.H., I.J.W., J.S.E., and D.-M.R. ; investigation, H.Y.A., S.S., and U.H. ; formal analysis, H.Y.A., S.S., and U.H. ; resources, I.J.W. and J.S.E; project administration, D.-M.R. ; writing--original draft preparation, H.Y.A., S.S., U.H., I.J.W., J.S.E., and D.-M.R. ; writing--review and editing, H.Y.A., S.S., U.H., I.J.W., J.S.E., and D.-M.R. All authors have read and agreed to the published version of the manuscript. This work was supported by the Biomedical Research Institute Grant, grant number 2019B022, Pusan National University Hospital. The authors declare no conflict of interest.