Effect Of Iron Chelator On Local Iron Deposition In Intramyocardial Hemorrhage After Acute Myocardial Infarction

Objective:This study mainly investigated the effects of iron chelating agent deferrone(DFP)on early iron metabolism,local iron deposition in myocardial tissue and myocardial injury in the rat model of internal myocardial hemorrhage(IMH),evaluated the effects of DFP on iron metabolism after IMH and local iron deposition in myocardial infarction region,and provided partial reference for the application of DFP in IMH treatment.And provide some theoretical basis for clinical study of IMH.Methods:In this study,eight-week-old male SD rats were randomly divided into four groups:Sham operation blank control group(Sham group),Sham operation single drug administration group(Sham+DFP group),model group(IMH group)and experimental group(IMH+DFP group).There were 6 rats in Sham group and Sham+DFP group each,and 9 rats in IMH group and IMH+DFP group each,with a total of 30 rats.The rats in IMH group and IMH+DFP group were ligated with the left anterior descending coronary artery(LAD)for 90 minutes by thoracotomy,and the ECG of the rats showed obvious ST segment elevation,indicating successful ischemia induction.After 90 minutes,the cord was cut to restore the blood supply to the LAD.In Sham group and Sham+DFP group,the same procedure was performed,but only the LAD was ligated.After LAD reperfusion,rats were given gavage immediately.Sham+DFP and IMH+DFP groups were given DFP(100mg/kg/d),Sham group and IMH groups were given the same amount of normal saline.The rats were sacrificed 24 h after reperfusion.Blood was collected for determination of serum iron related indexes,and heart was used for determination of tissue iron,myocardial infarction area detection and histomorphological observation.Graphpad Prism8.0.2 was used for statistical analysis and histogram drawing.T-test or Mann-Whitney U test was used for comparison between the two groups.Single-factor ANOVA was used for multi-group comparison,and Bonferroni method was used for pairwise comparison,and P < 0.05 was considered as statistically significant.Results:In Sham group and Sham+DFP group,HE staining showed normal structure arrangement of myocardial fibers,no obvious inflammatory cell infiltration in myocardial interstitium,no large amount of RBC extravasation in myocardial,and no iron was found in Perl staining.In IMH group and IMH+DFP group,HE staining showed that the normal arrangement and structure of myocardial fibers disappeared,and the myocardial fibers in some areas were disorganized,with coagulated necrosis of myocardial cells and disappearance of nucleolysis.A large number of red blood cells exudated and lymphocytes infiltrated in the interstitium of cells.Perl staining confirmed the presence of iron deposition in myocardial tissue.The success of IMH modeling was verified from histological level.1.SI in Sham group was significantly higher than that in Sham+DFP group and IMH+DFP group(P < 0.0001),and SI in IMH group was significantly higher than that in IMH+DFP group(P < 0.0001),but there was no significant difference between IMH group and Sham group(P>0.05).2.There was no significant difference in TIBC among all groups(P>0.05).However,there was no statistical difference among all groups(P >0.05).3.The TS in Sham group was significantly higher than that in Sham+DFP group and IMH+DFP group(P < 0.001),and the TS in IHM group was generally higher than that in IMH+DFP group,the difference being statistically significant(P < 0.0001).4.Iron content in myocardial tissue of rats in IMH group was significantly higher than that in other groups(P<0.001),while iron content in myocardial tissue of rats in Sham group was slightly higher than that in Sham+DFP group,but there was no statistical significance(P>0.05).5.No myocardial infarction occurred in sham group and Sham +DFP group.There was no significant difference in myocardial infarction volume ratio between IMH group and IMH+DFP group(P > 0.05).Conclusion:DFP can significantly reduce SI and TS,but has little effect on the TIBC of rats.DFP can significantly reduce the iron content in the tissue at the site of myocardial infarction,which has a positive effect on alleviating local iron deposition caused by IMH,but DFP cannot limit the volume of myocardial infarction.