Experimental And Treatment Research In Rats Arterial Embolism After Hyaluronic Acid Injection

Objective:With the rapid development of aesthetic medicine and biomaterial,hyaluronic acid filler has become the most frequently used among soft tissue fillers。AS the IS APS reported that the number of hyaluronic acid injection increased more than 9%from 2010 to 2016.In fact,the total number of hyaluronic acid injection in 2016 was 28.7 million,of which was 1.6 million in 2010.This number is expected to continue to grow.Although the HA fillers used today have a great safety profile with minimal adverse events,with increased clinical applications of these fillers and the increased number of procedures performed,the number of severe and detrimental adverse events is on the rise.HA injection related adverse reaction is classified into minor and major complications.Major complications were primarily due to arterial occlusion,may lead to tissue necrotic,blindness,stroke or even death.Most of these serious complications does not resolve spontaneously.Although the events seldom happen,however,with rapidly growing number of procedures performed and expanding application,its complications are far from adequate attention.Our study consisting of two experiments was designed to explore the optimal treatment program of HA-related vascular occlusion,establishment and experimental research of animal model are of profound significance for directing clinical treatment of these complications.Methods:Part I:30 SD rats were injected approximately 0.02 milliliters of HA into bilateral inferior epigastria arteries after anesthetized as animal model and divided randomly into 6 groups.Execution each group at 0min,15min,45min,3h,24h,and 48h after the injection.The inferior epigastric artery was removed,fix,slice and stain for pathological examination.Part II:As animal model,6 groups within 10 male SD rats include were anesthetized,flaps on both side of the lower abdomen nourished by the inferior epigastric artery were elevated.Approximately 0.02 milliliters of HA were injected into the right inferior epigastric artery and the left side keep untouched as a blank control.Each group was given a different solution as follows:Solution was injected intravenously though the tail vein or subcutaneous around the artery area according to grouping.Photographs of flaps were taken at 0,4,12,24,72 and 168h(lweek)after injection.The occurrence rate of flap necrosis was calculated and analyzed.The right inferior epigastric artery was remove for pathological examination after executed.Result:Part Ⅰ:Omin:The artery was distended and occluded by HA embolus,without platelet fibrin thrombi.15min:The artery was distended and occluded by HA embolus with tail mix with fresh thrombus,white thrombus was shown in the vessel.45min:The artery was distended and occluded by HA embolus with tail surrounding by fresh thrombus,numerous white thrombus was shown in the vessel.3h:The artery was distended and occluded by white thrombus as well as HA embolus with fresh thrombus occurred on the head and surrounded the tail.24h:The artery was distended and occluded by HA embolus which totally wrapped by thrombus,thrombosis was observed in full-length of the vessel.48h:The artery was occluded by HA and thrombus,white thrombus comprised the tail of the embolus with mixed thrombus of the rest.Trend of organize were observed by now.Part Ⅱ:Flap survival rate(Mean percentage):Group A:43.29±9.28%,Group B:54.17±10.86%,Group C:59.27±13.40%,Group D:64.37±8.61%,Group E:71.92±19.06%,Group F:57.47±13.64%。Group A showed a distinct difference compared with Group B,C,D,E(p<0.001),Group A and Group F(p<0.001),there was no significant difference among these two groups.Conclusion:1.We presume the process of arterial thrombosis associated with HA injection as follow:When HA filler entered the artery,the clotting process were initiated to start the formation of the thrombus.45min after the injection,tail of the embolus were surrounding by fresh thrombus,by 24 hours,thrombus was wrapping completely around the HA embolus and early stage of thrombus organization can be found at 48 hours.2.Treatment combines hyaluronidase and urokinase or using either drugs alone was usually effective within 45min when thrombus embolism occurs.Combine use of both drugs gain the optimal medicinal effects.3.Combined use of hyaluronidase and urokinase has best efficacy of treating HA injection related arterial embolism when 45min and 24 hours after occurs and the treatment might be ineffective after 48hours.