Volume 7, Issue 1, Pages (January 2010)

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Volume 7, Issue 1, Pages 110-116 (January 2010) Induction of atrial ectopic beats with calcium release inhibition: Local hierarchy of automaticity in the right atrium Tetsuji Shinohara, MD, PhD, Boyoung Joung, MD, PhD, Daehyeok Kim, MD, PhD, Mitsunori Maruyama, MD, PhD, Hsiang-Ning Luk, MD, PhD, Peng-Sheng Chen, MD, FHRS, Shien-Fong Lin, PhD Heart Rhythm Volume 7, Issue 1, Pages 110-116 (January 2010) DOI: 10.1016/j.hrthm.2009.09.068 Copyright © 2010 Heart Rhythm Society Terms and Conditions

Figure 1 The effect of ryanodine on intact SAN. A: Changes of cycle length by ryanodine infusion. *P <.05 vs. baseline. B: Effects of ryanodine on isoproterenol-induced cycle length decrease. *P <.05, **P <.01 vs. corresponding isoproterenol-only group. C: Sinus node recovery time at the baseline and with ryanodine. D: Correct sinus node recovery time at the baseline and with ryanodine. cSNRT = corrected sinus node recovery time; ISO = isoproterenol; Ryd = ryanodine; SNRT = sinus node recovery time; SAN = sinoatrial node. Heart Rhythm 2010 7, 110-116DOI: (10.1016/j.hrthm.2009.09.068) Copyright © 2010 Heart Rhythm Society Terms and Conditions

Figure 2 The change of the activation pattern of the SAN by ryanodine. A: The isolated RA preparation showing the SAN and surrounding RA. The gray area is the SAN. B: Activation pattern of the SAN and surrounding RA under basal condition. The color picture shows an isochronal map of Vm propagation. The Cai (red) and Vm (black) recordings from the superior (S), middle (M), and inferior (I) SAN are presented. C: Magnified view of Cai tracing of middle SAN. D: Activation pattern of SAN and surrounding RA during ryanodine infusion of 3 μmol/l. E: Effect of ryanodine (3 μmol/l) on the slope of LDCAE. Arrows point to LDCAE. The activation patterns presented in B and D are from the area in the circle in A. Cai = intracellular calcium; IVC = inferior vena cava; LDCAE = late diastolic intracellular calcium elevation; RA = right atrium; SVC = superior vena cava; Vm = transmembrane potential; other abbreviations as in Figure 1. Heart Rhythm 2010 7, 110-116DOI: (10.1016/j.hrthm.2009.09.068) Copyright © 2010 Heart Rhythm Society Terms and Conditions

Figure 3 Effect of isoproterenol on the activation pattern of SAN. A: Isoproterenol (0.1 μmol/l)-induced activation pattern of SAN. Color picture shows an isochronal map of Vm. The Cai (red) and Vm (black) recordings from the superior (S), middle (M), and inferior (I) SAN are presented. B: Magnified view of a Cai tracing of the superior SAN. C: Effect of isoproterenol (0.1 μmol/l) on the slope of LDCAE. Arrows point to LDCAE. Abbreviations as in Figure 2. Heart Rhythm 2010 7, 110-116DOI: (10.1016/j.hrthm.2009.09.068) Copyright © 2010 Heart Rhythm Society Terms and Conditions

Figure 4 Activation pattern of AEP. A: Locations of the ectopic beats on the epicardial side. Circles show the sites of ectopic beats. White circles represent ectopic beats continuing for more than 30 seconds. Red circles represent ectopic beats continuing for fewer than 30 seconds. Yellow circles correspond with those in B. B: Activation isochrones of an ectopic beat from epicardium. Isochronal map shows epicardial activation pattern of Vm during the ectopic beat. The Cai (red) and Vm (black) recordings from the ectopic pacemaking site (a) and surrounding sites (b and c) are presented; a, b, and c in Vm and Cai recordings correspond with those indicated in the isochronal map. C: Locations of the ectopic beats sites from the endocardium side. D: Activation isochrones of an ectopic beat from endocardium. Arrows show the diastolic depolarizations. AEP = atrial ectopic pacemaker; other abbreviations as in Figure 2. Heart Rhythm 2010 7, 110-116DOI: (10.1016/j.hrthm.2009.09.068) Copyright © 2010 Heart Rhythm Society Terms and Conditions

Figure 5 The change of heart rate with drug treatments. Heart rate was decreased by ryanodine infusion. Isoproterenol induced ectopic beats from the lower crista terminalis and marginal increase of heart rate. An ZD7288 infusion of 3 or 30 μmol/l suppressed the rate of ectopic beats. n = 3, respectively. Abbreviations as in Figure 2. Heart Rhythm 2010 7, 110-116DOI: (10.1016/j.hrthm.2009.09.068) Copyright © 2010 Heart Rhythm Society Terms and Conditions

Figure 6 Spontaneous cycle length with drug treatments. Bars show = cycle lengths induced by different pharmacological interventions; Ryd = 3.0 μmol/L ryanodine; ISO = 1.0 μmol/L isoproterenol; low ZD and ZD = 3 and 30 μmol/L ZD7288, respectively. *P <0.05 and **P <0.01 vs. baseline. Abbreviations as in Figure 2. Heart Rhythm 2010 7, 110-116DOI: (10.1016/j.hrthm.2009.09.068) Copyright © 2010 Heart Rhythm Society Terms and Conditions