- 期刊
Repolarization Reserve in Cardiac Cells
並列摘要
Repolarization reserve is a term used to indicate the existence of redundancy of repolarizing currents in cardiac cells. It provides safety and prevents cardiac arrhythmias due to excessive prolongation of the action potential duration (APD) and generation of early afterdepolarizations. The existence of repolarization reserve in cardiac cells and its modulation is the main topic of this short review. Under physiological conditions repolarization reserve is modulated by increase of frequency, sympathetic stimulation and the accompanying rise in [Ca(superscript 2+)](subscript i), [Na(superscript +)](subscript i) and [K(superscript +)](subscript e). The analysis of the changes by frequency and activation of the sympathetic system reveals an increase in repolarization reserve. At elevated rates APD shortening is caused by enhancement of outward currents (I(subscript Kr) I(subscript Ks) and I(subscript Na,K)), while inward currents are decreased (I(subscript Na,late) and I(subscript CaL) due to faster inactivation; peak I(subscript CaL) may be increased by acceleration of recovery from inactivation). Under sympathetic stimulation not only sinus rate increases but specific effects occur at the ventricular level by activation of α- and β-receptors. Major effects occur via activation of β-receptors which result in an increase of .I(subscript CaL), I(subscript Kr), I(subscript Ks) and I(subscript Na,K), elevation of the plateau and further shortening of the APD. Pathological reduction of repolarization reserve with increased risk of deadly arrhythmias can be of hereditary (congenital LQTsyndromes) or of an acquired nature. One of the more frequent and dangerous forms of acquired LQT is caused by the use of medications. The drugs responsible belong to different groups but have the common effect of blocking K(superscript +) currents. Since not all patients using these drugs show complications of arrhythmias attention should be given to the underlying risk factors, such as hypokalemia, hypomagnesemia, female sex, predisposing DNA polymorphisms, congestive heart failure, left ventricular hypertrophy. It is the aim of future research, especially in the case of hypertrophy and failure to unravel the remodeling mechanisms responsible for increased risk. In this way it will become possible to prevent excessive reduction of repolarization reserve and to preserve a normal repolarization.