Browsing by Author "Chua, Su-Kiat"

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    Hypokalemia Promotes Late Phase 3 Early Afterdepolarization and Recurrent Ventricular Fibrillation During Isoproterenol Infusion in Langendorff Perfused Rabbit Ventricles
    (Elsevier, 2014-04) Maruyama, Mitsunori; Ai, Tomohiko; Chua, Su-Kiat; Park, Hyung-Wook; Lee, Young-Soo; Shen, Mark J.; Chang, Po-Cheng; Lin, Shien-Fong; Chen, Peng-Sheng; Department of Medicine, IU School of Medicine
    BACKGROUND Hypokalemia and sympathetic activation are commonly associated with electrical storm (ES) in normal and diseased hearts. The mechanisms remain unclear. OBJECTIVE To test the hypothesis that late phase 3 early afterdepolarization (EAD) induced by IKATP activation underlies the mechanisms of ES during isoproterenol infusion and hypokalemia. METHODS Intracellular calcium (Cai) and membrane voltage were optically mapped in 32 Langendorff-perfused normal rabbit hearts. RESULTS Repeated episodes of electrically-induced VF at baseline did not result in spontaneous VF (SVF). During isoproterenol infusion, SVF occurred in 1 of 15 hearts (7%) studied in normal extracellular potassium ([K+]o) (4.5 mmol/L), 3 of 8 hearts (38%) in 2.0 mmol/L [K+]o, 9 of 10 hearts (90%) in 1.5 mmol/L [K+]o, and 7 of 7 hearts (100%) in 1.0 mmol/L [K+]o (P<0.001). Optical mapping showed isoproterenol and hypokalemia enhanced Cai transient duration (CaiTD) and heterogeneously shortened action potential duration (APD) after defibrillation, leading to late phase 3 EAD and SVF. IKATP blocker (glibenclamide, 5 μmol/L) reversed the post-defibrillation APD shortening and suppressed recurrent SVF in all hearts studied despite no evidence of ischemia. Nifedipine reliably prevented recurrent VF when given before, but not after, the development of VF. IKr blocker (E-4031) and small conductance calcium activated potassium channel blocker (apamin) failed to prevent recurrent SVF. CONCLUSION Beta-adrenergic stimulation and concomitant hypokalemia could cause non-ischemic activation of IKATP, heterogeneous APD shortening and prolongation of CaiTD to provoke late phase 3 EAD, triggered activity and recurrent SVF. IKATP inhibition may be useful in managing ES during resistant hypokalemia.
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    Selective sinoatrial node optical mapping and the mechanism of sinus rate acceleration
    (J-Stage, 2012) Shinohara, Tetsuji; Park, Hyung-Wook; Joung, Boyoung; Maruyama, Mitsunori; Chua, Su-Kiat; Han, Seongwook; Shen, Mark J.; Chen, Peng-Sheng; Lin, Shien-Fong; Department of Medicine, IU School of Medicine
    BACKGROUND: Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum calcium release (Ca clock) plays an important role in SAN automaticity. In the intact SAN, cross-contamination of optical signals from the SAN and the right atrium (RA) prevent the definitive testing of Ca clock hypothesis. The aim of this study was to use a novel approach to selectively mapping the intact SAN to examine the Ca clock mechanism. METHODS AND RESULTS: We simultaneously mapped intracellular Ca (Ca(i)) and membrane potential (V(m)) in 10 isolated, Langendorff-perfused normal canine RAs. The excitability of the RA was suppressed with high-potassium Tyrode's solution, allowing selective optical mapping of V(m) and Ca(i) of the SAN. Isoproterenol (ISO, 0.03 µmol/L) decreased the cycle length of the sinus beats, and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Ca(i) upstroke preceded the V(m) in the leading pacemaker site by up to 18 ± 2 ms. ISO-induced changes to SAN were inhibited by ryanodine (3 µmol/L), but not ZD7288 (3 µmol/L), a selective I(f) blocker. CONCLUSIONS: We conclude that, in the isolated canine RA, a high extracellular potassium concentration can suppress atrial excitability thus leading to SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation.