Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders,syncope,and even death.Up to now,the best way to treat it is to implant electronic pacemakers.However,these have ma...Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders,syncope,and even death.Up to now,the best way to treat it is to implant electronic pacemakers.However,these have many disadvantages such as limited battery life,infection,and fixed pacing rate.There is an urgent need for a biological pacemaker(bio-pacemaker).This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion.Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches.The former mainly includes gene therapy and cell therapy,whilst the latter involves the use of multi-scale computer models of the heart,ranging from the single cell to the tissue slice.Up to now,a bio-pacemaker has been successfully applied in big mammals,but it still has a long way from clinical uses for the treatment of human heart diseases.It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process.Finally,we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.展开更多
Loss of function and gain of function mutations of the sodium channel were investigated using an intact two-dimensional rabbit sinoatrial node (SAN) and atrial cell model. The effects of three external stimuli (acetyl...Loss of function and gain of function mutations of the sodium channel were investigated using an intact two-dimensional rabbit sinoatrial node (SAN) and atrial cell model. The effects of three external stimuli (acetylcholine secretion by the vagal nerve, acid-base concentration, and tissue temperature) on cardiac pacemaker function and conduction were studied. Our results show that these two groups of mutations have different effects on pacemaker function and conduction. Furthermore, we found that the negative effects of these mutations could be altered by external stimuli. The bradycardic effects of mutations were magnified by an increase in acetylcholine level. Changes in acid-base concentration and tissue temperature increased the ability of the SAN to recover its pacemaker function. The results of this study increase our understanding of sodium channel disorders, and help to advance research on the treatment of these conditions.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.61572152,61601143,and 81770328)the Science Technology and Innovation Commission of Shenzhen Municipality(Nos.JCYJ20151029173639477 and JSGG20160229125049615)the China Postdoctoral Science Foundation(No.2015M581448)。
文摘Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders,syncope,and even death.Up to now,the best way to treat it is to implant electronic pacemakers.However,these have many disadvantages such as limited battery life,infection,and fixed pacing rate.There is an urgent need for a biological pacemaker(bio-pacemaker).This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion.Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches.The former mainly includes gene therapy and cell therapy,whilst the latter involves the use of multi-scale computer models of the heart,ranging from the single cell to the tissue slice.Up to now,a bio-pacemaker has been successfully applied in big mammals,but it still has a long way from clinical uses for the treatment of human heart diseases.It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process.Finally,we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.
基金supported by the National Natural Science Foundation for Theoretical Physics of China (11047017)the Wellcome Trust (081808/Z/06/Z)+1 种基金the Biotechnology and Biological Sciences Research Council (BBS/B1678X), UKthe Special Foundation of Education of Anhui Province for Excellent Young Scientists (2011SQRL023)
文摘Loss of function and gain of function mutations of the sodium channel were investigated using an intact two-dimensional rabbit sinoatrial node (SAN) and atrial cell model. The effects of three external stimuli (acetylcholine secretion by the vagal nerve, acid-base concentration, and tissue temperature) on cardiac pacemaker function and conduction were studied. Our results show that these two groups of mutations have different effects on pacemaker function and conduction. Furthermore, we found that the negative effects of these mutations could be altered by external stimuli. The bradycardic effects of mutations were magnified by an increase in acetylcholine level. Changes in acid-base concentration and tissue temperature increased the ability of the SAN to recover its pacemaker function. The results of this study increase our understanding of sodium channel disorders, and help to advance research on the treatment of these conditions.
