Search

Abstract: Objectives: Although previous studies in dogs have indicated a minimal role for changes in I K1 in the shortening of action potential duration (APD) associated with atrial fibrillation (AF), in humans, there is evidence for significant AF-induced up-regulation of this current. In this computer model study, we investigated the relative contributions of the remodeling of I K1, L-type calcium current, and other remodeled ionic channel currents to AF-induced APD reduction in human atrium. Methods: Two computer models of electrical activity of human atrial cell were modified by incorporating experimental data of AF-induced changes in human atrial ionic channel conductance and kinetics reported by Bosch et al. (I CaL, I to, I K1, and I Na) (AF-1) and Workman et al. (I CaL, I to, and I K1) (AF-2). The roles and relative importance of individually remodeled ion channels in the APD reduction in human atrium were evaluated by the removal and exclusive methods, in which remodeling of specific currents was omitted, or considered in isolation, in the two models. Results: When tested together, previously reported AF-induced changes in sarcolemmal ion currents result in marked shortening of atrial APD90. With the AF-1 remodeled parameters, there is a 62% reduction in APD90 for the Nygren et al. model, and a 68% reduction for the Courtemanche et al. model, which are comparable to experimental results of 60% reduction seen in humans. When tested individually, AF-1-induced changes in I CaL, I K1, or I to alone result in APD90 reduction of 20%, 64%, and −10%, respectively, for the Nygren et al. model, and 27%, 40%, and 11.6%, respectively, for the Courtemanche et al. model. With the AF-2 remodeled parameters, there is a 47% reduction in APD90 for the Nygren et al. model and a 49% reduction for the Courtemanche et al. model, which are also comparable to experimental results of 45% reduction. When tested individually, AF-2-induced changes in I CaL or I K1 alone result in APD90 reduction of 20% and 40%, respectively, for the Nygren et al. model, and 14% and 21%, respectively, for the Courtemanche et al. model. Conclusion: Previously reported changes in L-type Ca2+ current are insufficient to account for the observed reduction in atrial APD associated with persistent AF. Up-regulation of I K1 has a greater influence on atrial APD in the human model. [Copyright &y& Elsevier]

Objective: The aim was to assess the effects of therapeutic doses of intravenous adenosine on human atrial and ventricular repolarisation. Methods: The effects of 6 mg and 12 mg bolus doses of adenosine on the atrial and ventricular monophasic action potentials were studied using the contact catheter technique in 19 patients undergoing routine diagnostic electrophysiology studies. The effect on atrial repolarisation was studied before and after β blockade in a subgroup of patients. Results: The duration of the monophasic action potential to 90% repolarisation (MAPD90) was measured in all cases. After 6 mg of adenosine the atrial MAPD90 shortened from 227(SD 29) ms to 188(25) ms (p<0.005); after 12 mg it shortened from 221(31) ms to 168(32) ms (p<0.001). The maximum shortening was unaltered by propranolol 0.15 mg·kg−1. The ventricular MAPD90 showed no significant change after 12 mg, at 240(32) ms v 234(33) ms. Conclusions: Therapeutic doses of adenosine shorten the atrial but not the ventricular monophasic action potential duration. The effect is dose dependent and not abolished by β blockade.Cardiovascular Research 1992;26:939–943 [ABSTRACT FROM PUBLISHER]

Objectives: Although previous studies in dogs have indicated a minimal role for changes in I(K1) in the shortening of action potential duration (APD) associated with atrial fibrillation (AF), in humans, there is evidence for significant AF-induced up-regulation of this current. In this computer model study, we investigated the relative contributions of the remodeling of I(K1), L-type calcium current, and other remodeled ionic channel currents to AF-induced APD reduction in human atrium., Methods: Two computer models of electrical activity of human atrial cell were modified by incorporating experimental data of AF-induced changes in human atrial ionic channel conductance and kinetics reported by Bosch et al. (I(CaL), I(to), I(K1), and I(Na)) (AF-1) and Workman et al. (I(CaL), I(to), and I(K1)) (AF-2). The roles and relative importance of individually remodeled ion channels in the APD reduction in human atrium were evaluated by the removal and exclusive methods, in which remodeling of specific currents was omitted, or considered in isolation, in the two models., Results: When tested together, previously reported AF-induced changes in sarcolemmal ion currents result in marked shortening of atrial APD(90). With the AF-1 remodeled parameters, there is a 62% reduction in APD(90) for the Nygren et al. model, and a 68% reduction for the Courtemanche et al. model, which are comparable to experimental results of 60% reduction seen in humans. When tested individually, AF-1-induced changes in I(CaL), I(K1), or I(to) alone result in APD(90) reduction of 20%, 64%, and -10%, respectively, for the Nygren et al. model, and 27%, 40%, and 11.6%, respectively, for the Courtemanche et al. model. With the AF-2 remodeled parameters, there is a 47% reduction in APD(90) for the Nygren et al. model and a 49% reduction for the Courtemanche et al. model, which are also comparable to experimental results of 45% reduction. When tested individually, AF-2-induced changes in I(CaL) or I(K1) alone result in APD(90) reduction of 20% and 40%, respectively, for the Nygren et al. model, and 14% and 21%, respectively, for the Courtemanche et al. model., Conclusion: Previously reported changes in L-type Ca(2+) current are insufficient to account for the observed reduction in atrial APD associated with persistent AF. Up-regulation of I(K1) has a greater influence on atrial APD in the human model.