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Heart Rate Acceleration of a Subsidiary Pacemaker by β-Adrenergic Stimulation

 Sanghoon Park  ;  Hyerim Park  ;  Boyoung Joung  ;  Moon-Hyoung Lee  ;  Hui-Nam Pak  ;  Jong-Youn Kim  ;  Jung-Hoon Sung  ;  Jaemin Shim  ;  Hye Jin Hwang 
 Korean Circulation Journal, Vol.41(11) : 658-665, 2011 
Journal Title
 Korean Circulation Journal 
Issue Date
BACKGROUND AND OBJECTIVES: Recent evidence indicates that the membrane voltage and Ca(2+) 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 Ca(i) 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) Ca(2+) 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 Ca(2+) emptying (n=3). CONCLUSION: Acceleration of the Ca(2+) 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.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김종윤(Kim, Jong Youn) ; 박희남(Pak, Hui Nam) ; 심재민(Shim, Jae Min) ; 이문형(Lee, Moon Hyoung) ; 정보영(Joung, Bo Young) ; 황혜진(Hwang, Hye Jin)
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