%0 Journal Article %1 Sipi_2006_159 %A Sipido, K. R. %A Varro, A. %A Eisner, D. %D 2006 %J Handb Exp Pharmacol %K Action Agents; Aniline Animals; Anti-Arrhythmia Arrhythmia; Calcium; Cardiomegaly; Compounds; Congestive; Ethers; Exchanger; Failure, Heart Heart; Humans; Myocardium; Phenyl Potentials; Sodium-Calcium Thiourea %N 171 %P 159--199 %T Sodium calcium exchange as a target for antiarrhythmic therapy. %V 171 %X In search of better antiarrhythmic therapy, targeting the Na/Ca exchanger is an option to be explored. The rationale is that increased activity of the Na/Ca exchanger has been implicated in arrhythmogenesis in a number of conditions. The evidence is strong for triggered arrhythmias related to Ca$^2+$ overload, due to increased Na$^+$ load or during adrenergic stimulation; the Na/Ca exchanger may be important in triggered arrhythmias in heart failure and in atrial fibrillation. There is also evidence for a less direct role of the Na/Ca exchanger in contributing to remodelling processes. In this chapter, we review this evidence and discuss the consequences of inhibition of Na/Ca exchange in the perspective of its physiological role in Ca$^2+$ homeostasis. We summarize the current data on the use of available blockers of Na/Ca exchange and propose a framework for further study and development of such drugs. Very selective agents have great potential as tools for further study of the role the Na/Ca exchanger plays in arrhythmogenesis. For therapy, they may have their specific indications, but they carry the risk of increasing Ca$^2+$ load of the cell. Agents with a broader action that includes Ca$^2+$ channel block may have advantages in other conditions, e.g. with Ca$^2+$ overload. Additional actions such as block of K$^+$ channels, which may be unwanted in e.g. heart failure, may be used to advantage as well.

@article{Sipi_2006_159, abstract = {In search of better antiarrhythmic therapy, targeting the Na/Ca exchanger is an option to be explored. The rationale is that increased activity of the Na/Ca exchanger has been implicated in arrhythmogenesis in a number of conditions. The evidence is strong for triggered arrhythmias related to {C}a$^{2+}$ overload, due to increased {N}a$^{+}$ load or during adrenergic stimulation; the Na/Ca exchanger may be important in triggered arrhythmias in heart failure and in atrial fibrillation. There is also evidence for a less direct role of the Na/Ca exchanger in contributing to remodelling processes. In this chapter, we review this evidence and discuss the consequences of inhibition of Na/Ca exchange in the perspective of its physiological role in {C}a$^{2+}$ homeostasis. We summarize the current data on the use of available blockers of Na/Ca exchange and propose a framework for further study and development of such drugs. Very selective agents have great potential as tools for further study of the role the Na/Ca exchanger plays in arrhythmogenesis. For therapy, they may have their specific indications, but they carry the risk of increasing {C}a$^{2+}$ load of the cell. Agents with a broader action that includes {C}a$^{2+}$ channel block may have advantages in other conditions, e.g. with {C}a$^{2+}$ overload. Additional actions such as block of {K}$^{+}$ channels, which may be unwanted in e.g. heart failure, may be used to advantage as well.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Sipido, K. R. and Varro, A. and Eisner, D.}, biburl = {https://www.bibsonomy.org/bibtex/2bc82c0612c9ea2b77dbac35755cd8785/hake}, description = {The whole bibliography file I use.}, interhash = {b206d8c51389f5cc67458e845b61a3b7}, intrahash = {bc82c0612c9ea2b77dbac35755cd8785}, journal = {Handb Exp Pharmacol}, keywords = {Action Agents; Aniline Animals; Anti-Arrhythmia Arrhythmia; Calcium; Cardiomegaly; Compounds; Congestive; Ethers; Exchanger; Failure, Heart Heart; Humans; Myocardium; Phenyl Potentials; Sodium-Calcium Thiourea}, number = 171, pages = {159--199}, pmid = {16610344}, timestamp = {2009-06-03T11:21:30.000+0200}, title = {Sodium calcium exchange as a target for antiarrhythmic therapy.}, volume = 171, year = 2006 }