Histopathological Study And Expression Of Ryanodine Receptor 2 In The Cardiac Conduction System Of Sudden Cardiac Death

Background Sudden cardiac death (SCD) was the emphasis and difficulty of forensicpathology's research and practice. Although causes for death could be found in most cases, some of them could not be found by means of the inspection of forensicpathology, which was named as negative autopsy. This thesis aimed to make a deep investigation of the symptoms prior to death in negative autopsy cases and find out some attentions to heart incidents, so as to identify the death as SCD. Taking the symptoms of prior to death and the inspection results of forensicpathology into account, most scholars hold that this kind of death is related to some deadly arrhythrmia disease. After the molecular biological research of tissue samples from the dead and the pathophysiological research of experimental animals, researchers at home and abroad assumed that the fatal arrhythrmia disease were related to the mutation of the coding gene of the ion channel. Meanwhile, there were some abnormal expression and distribution of proteins of ion channel in some kinds of arrhythmia diseases.The cardiac conduction system was the system to start and conduct electrocardiac activities, which includes sinuatrial node(SAN), atrioventricular node(AVN), His bundle, bundle branch(BB), etc. The pathological changes of cardiac conduction system could directly cause disorder of electrocardiac activities, namely arrhythmia.Ryanodine Receptor 2 (RyR2) was the main release channel for calcium in sarcoplasmic reticulum of cadiocyte and played an important role in excitation-contractioncouple activities. Numerous studies confirmed that abnormal expression and disorder of RyR2 might lead to many types of fatal arrhythmia diseases. However, current researchs were mainly carried out by means of molecular biology, focused on inspection of genetic mutation, genes and expression of proteins. These methods might be precise but difficult to be applied extensively in real forensic pathology for the autolysis of samples tested. Immunohistochemistry was much more practical in that it called for less requirements than molecular biology and no special instruments for inspection. Nevertheless, no study had been reported on the expression and distribution of cardiac conduction system RyR2 by means of immunohistochemistry till now.Objectives This study was first to collect the SCD cases inspected in our investigation and research section and extract the tissue from the cardiac conduction system. And after it was sliced and stained with HE and immunohistochemically, the pathomorphological arthroscopic change of sinoauricular node, atrioventricular node and His bundle as well as the coloring of RyR2 would be observed and compared with non-SCD group, and thus finding out the differences between the two groups, so as to offer some suggestions for the forensic pathological diagnosis of some negative autopsy of sudden deaths and its research.Material and Methods The samples was sorted out to be 2 groups, SCD group and non-SCD group. All the samples came from the autopsies at the Teaching and Research Section of Forensic Pathology, Forensic Medicine Department, Tongji Medical College, HUST. The SCD group had 23 samples, identified as SCD by means of systematic forensic pathologyical inspection and case investigation while non-SCD group had 14 cases, with mechanical injury, mechanical asphyxia etc. as their death causes. First, tissue would be cut and sliced from SAN, AVN, His bundle in the cardiac conduction system. On the basis of observation of HE stain, further study would be made on the immunohistochemical coloring of RyR2. And then a comparison and graphical analysis of pathomorphological change and immunohistochemical coloring of the cardiac muscle and interstitial substance was made between the two groups.Results The rate of pathological changes in cardiac conduction system in SCD group was higher than in non-SCD. The main Pathological changes in SCD group were pathofibrosis or adipoe infiltration, haemorrhage, vessel wall troubles etc. The expression of RyR2 of the SCD group is significantly lower than of the non-SCD group , and it shows abnormal distribution both between cells and in the myocyte .Conclusions There would often be pathomorphological changes in the CCS of the SCDs . It would be helpful for the diagnosis of SCD to exam the CCS . The expression of RyR2 in SAN , AVN , His was signicicantly decreased , prompted that the mechanism of arrhythmia of SCD might have to do with the priming and conduction of electrocardiac activity in the CCS . The expression of RyR2 in the parts above-mentioned was signicicantly decreased , prompted that the IHC of RyR2 might be helpful for the diagnosis of SCD .