Introduction The mesenchymal cell populations present in the myocardium are often referred to as cardiac fibroblasts (CFs) and are distinct from fibroblasts present in other organs. CFs play many essential roles in the developing and adult heart by contributing to…
Current Guidelines for Cardiotoxicity and Proarrhythmia Screening Cardiotoxicity is a major reason for drug attrition and is thus a core subject in preclinical and clinical safety testing of new drugs. Cardiac safety testing of new chemical entities that become lead…
Cardiovascular disease continues to be the global leader when it comes to cause of death, despite a steadily declining mortality rate. In 2016, the global age-adjusted death rate had decreased by 14.5% compared with 2006. Cardiovascular disease often results in…
Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a frequent cause of stroke. , Despite its clinical importance, AF is a difficult condition to treat, with limited efficacy of current therapeutic strategies including antiarrhythmic drugs and…
DefiNing Phenotype The terms genotype and phenotype were introduced by the Danish plant physiologist and geneticist Wilhelm Johannsen in 1909. The genotype refers to parts or all of the genetic material, whereas the phenotype may be made up of any…
Introduction Individuals vary widely in their responses to therapy with most drugs. Indeed, response to cardiovascular drug therapy, and antiarrhythmics in particular, is so highly variable that studying the underlying mechanisms has elucidated important lessons for understanding variable responses to…
Acknowledgments I thank Omer Berenfeld, David Filgueiras-Rama, Raphael Martins, Yoshio Takemoto, Rafael Ramirez, Jiang Jiang, and all other members of the Center for Arrhythmia Research of the University of Michigan who participated in the studies that are the focus of…
Physiologist Sidney Ringer realized in the 19th century that calcium (Ca 2+) is essential for cardiac contraction. Working with isolated frog hearts, he noticed that removal of Ca 2+ from the perfusion buffer stopped contraction, whereas its re-addition restored and…
Introduction KVLQT1 (now referred to as KCNQ1 ) and human ether-a-go-go related gene ( hERG; now referred to as KCNH2 ), each encoding a major cardiac K + channel, were among the first genes that were linked to an inheritable…
Acknowledgment We gratefully acknowledge support from NHLBI (HL47678 and HL138103), the W.W. Smith Chartibale Trust, and the Martha and Wistar Morris Fund. Introduction The J wave syndromes, consisting of Brugada syndrome (BrS) and early repolarization syndromes (ERS), have intrigued the…