心包腔作为靶向治疗心血管疾病潜在途径的探索性研究

Exploratory study on pericardial cavity as a potential pathway for targeted treatment of cardiovascular diseases

目的通过向心包腔注射亚甲蓝或碘海醇,观测两者经心外膜向心肌浸润程度与心包内留存时间,探究心包腔途径在开展靶向心血管治疗方案中的应用潜力。方法8只SD大鼠随机分为亚甲蓝组和对照组。两组大鼠开胸后经心包腔注射200μL亚甲蓝或生理盐水。60 min后心脏取材,观测亚甲蓝浸润情况。10只雄性比格犬随机分成心包组与静脉组。分别经心包或静脉途径注射碘海醇生理盐水混合剂。混合剂由5 ml碘海醇(350 mg I/ml)与5 ml 0.9%生理盐水均匀混合而成。分别在注射后1、3、5、10、20、30、60 min,用X射线拍摄心包与膀胱碘海醇显影状况,并记录各时间节点与实验前的灰度值比值。结果亚甲蓝组大鼠心外膜组织与血管呈深蓝色,心脏冠状横切面存在自心外膜向心内膜的心肌组织染色浸润。心包组犬心包灰度值与基线比值随时间呈下降趋势,注射混合剂后10 min出现膀胱显影,60 min呈现显影高峰。静脉组犬在注射混合剂后在3 min膀胱即出现阳性显影,并在20 min达显影高峰。两组犬膀胱灰度值与基线比值在5 min出现显著差异。心包组仅在心包穿刺时出现短暂室性心律失常。结论探究了物质在心包腔中的代谢过程并初步验证心包内物质排泄速率慢于静脉途径,心包很有可能为心血管疾病治疗提供一个有利的选择空间。

Objective By injecting methylene blue or iohexol into the pericardial cavity,we observed the degree of infiltration of the two substances into the myocardium through the epicardium and the retention time inside the pericardial cavity.This study aims to explore the application potential of the pericardial cavity as a route for targeted cardiovascular treatment.Methods Eight SD rats were randomly assigned to the methylene blue group and the control group.Animals in both groups were subjected to thoracotomy and 200μL of methylene blue or physiological saline was injected into the pericardial cavity.After 60 minutes,hearts were collected for observation of the extent of methylene blue infiltration.Ten male beagles were randomly divided into the pericardial group and the venous group,each group receiving an injection of a mixture of iohexol and physiological saline through either the pericardial cavity or vein.The mixture was prepared by uniformly blending 5ml of iohexol(350mg I/ml)and 5ml of 0.9% physiological saline.X-ray was used to observe the imaging of iohexol in the pericardium and bladder at 1,3,5,10,20,30,60 minutes after injection,and the ratio of the grayscale value at each time point to that before the experiment was recorded.Results The epicardial tissue and blood vessels of rats in the methylene blue group were colored deep blue and the coronal section of the heart showed staining infiltration from the epicardium to the endocardium.In the pericardial group of dogs,the grayscale value of the pericardium compared to the baseline showed a downward trend over time,bladder imaging appeared 10 minutes after the injection of the mixture,and reached a peak at 60 minutes.In the venous group of dogs,bladder imaging positivity emerged 3 minutes after the injection and reached a peak at 20 minutes.A significant difference in the ratio of bladder grayscale values to the baseline emerged between the two groups of dogs 5minutes after injection.In the pericardial group of dogs,transient ventricular arrhythmia occurred when the pericardium was punctured.Conclusion This study explored the metabolic process of substances in the pericardial cavity and preliminarily verified that the rate of substance excretion in the pericardium is slower than that through the venous route.The pericardium may provide a favorable choice for the treatment of cardiovascular diseases.