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KMID : 0368120110410110658
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Korean Circulation Journal
2011 Volume.41 No. 11 p.658 ~ p.665
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Heart Rate Acceleration of a Subsidiary Pacemaker by β-Adrenergic Stimulation
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Park Sang-Hoon
Park Hye-Rim
Hwang Hye-Jin
Shim Jae-Min
Sung Jung-Hoon
Kim Jong-Youn
Pak Hui-Nam
Lee Moon-Hyoung
Joung Bo-Young
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Abstract
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Background and Objectives : Recent evidence indicates that the membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. However, the mechanism of heart rhythm acceleration of the subsidiary pacemaker (SP) during β-adrenergic stimulation is still unknown. Here we tested the hypothesis that the heart rate acceleration of the SP by β-adrenergic stimulation involves synergistic interactions between both clock mechanisms.
Subjects and Methods : We performed optical mapping and pharmacological interventions in 15 isolated Langendorff-perfused canine right atriums (RA). The SP model was produced by ligation of the SAN artery at the mid portion of the sulcus terminalis.
Results: In the 6 RAs with an intact SAN, 1 μmol/L isoproterenol infusion increased the heart rate from 82±9 to 166±18 bpm (102%) with late diastolic Cai elevation (LDCAE) at the superior SAN. However, in the 6 SP models, the heart rate increased from 55±10 bpm to 106±11 bpm (92%, p=0.005) without LDCAE at the earliest activation site. The isoproterenol induced heart rate increase was reversed to 74±5 bpm (33% from baseline) by administering an infusion of the funny current blocker ZD 7288 (3 μmol/L, n=3), whereas, it was suppressed to 69±7 bpm (24% from baseline) by sarcoplasmic reticulum (SR) Ca2+ emptying with administering ryanodine (10 μmol/L) plus thapsigargin (200 nmol/L, n=3). The isoproterenol induced heart rate increase was completely abolished by combined treatment with funny current blocker and SR Ca2+ emptying (n=3).
Conclusion: Acceleration of the Ca2+ clock in the SP plays an important role in the heart rate acceleration during β-adrenergic stimulation, and this interacts synergistically with the voltage clock to increase the heart rate.
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KEYWORD
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Calcium channel, Sympathetic nervous system, Sinoatrial node
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