Cardiac electronic pacemakers and biological Pacemakers / 中国组织工程研究

ABSTRACT

BACKGROUND: The implantation of electronic devices has become the preferred treatment tor symptomatic bradyarrhythmias.However,there are many shortcomings in electronic pacemakers.The usage of molecular biology principle to develop biological pacemaker has become a topic of discussion in research.When sinoatrial node is lnhlblted,pacemaker effect runs by transfecting hyperpolarization-activated cyclic nucleotide-gated(HCN)channel gene of If current,overexprcssing HCN,and increasing inward current in diastolic phase of the heart.Construction of biological pacemakefs by gene therapy and cell therapy may become an optimal substitute of electronic pacemakers in the near future.OBJECTIVE:To sum up the research advancement in application of HCN channel gene to the development of biological pacemaker.RETRIEVAL STRATEGYThe relevant articles published between January 1979 and June 2007 were searched for in Pubmed database by researcher of this article with the key words of"hyperpolarization-activated cyclic nucleotide-gated chartnel,biological pacemaker"in English.157 articles were selected and reviewed by the inclusive cntena of① articles closely related with the application of HCN to the development of biological pacemaker;②the late articles and articles in anthority journals in the same field.Exclusive criterionrepetitive studies.LITERATURE EVALUATIONThe main sources of literatures were randomized clinical trial(RCT)on biological pacemaker by HCN.Among 36 selected articles,10 were reviews,and others were elementary expenInental studles.DATA SYNTHESIS:①Of all four HCN isoforms,HCNI,HCN2,and HCN4 are the main isoforms in the heart.HCN3 only expresses in embryonic pacemaker cells in a low level.HCN2 highly expressed in low pacing regions(Ventricular muscle),whereas HCN4 highly expressed in high pacing regions.Moreover,HCN2 are the main isoforms in the ventricle.Expression ratio of HCN2 to HCN4 is 51 in neonate rats and 131 in adult rats.②Defects in HCN channels may underlie sick-sinus syndrome.③Up to now,HCN genes of If current contribute importantly to the generataon of the regular pacemaker potential.CONCLUSION:Gene therapy and cell therapy have become an optimal approach to improve biological paccmakers.Application of HCN channel gene in development of biological pacemaker may hold great promlse In the treatment of chronic arhythmia.