Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Heart Rate Acceleration of a Subsidiary Pacemaker by $\beta$-Adrenergic Stimulation

  • Park, Sang-Hoon (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Park, Hye-Rim (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Hwang, Hye-Jin (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Shim, Jae-Min (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Sung, Jung-Hoon (Division of Cardiology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University) ;
  • Kim, Jong-Youn (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Pak, Hui-Nam (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Lee, Moon-Hyoung (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Joung, Bo-Young (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine)
  • Published : 2011.11.30
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Abstract

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 $\beta$-adrenergic stimulation is still unknown. Here we tested the hypothesis that the heart rate acceleration of the SP by $\beta$-adrenergic stimulation involves synergistic interactions between both clock mechanisms. Materials and Methods: We per-formed 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 ${\mu}mol$/L isoproterenol infusion increased the heart rate from 82${\pm}$9 to 166${\pm}$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${\pm}$10 bpm to 106${\pm}$11 bpm (92%, p=0.005) without LDCAE at the earliest activation site. The isoproterenol induced heart rate increase was reversed to 74${\pm}$5 bpm (33% from baseline) by administering an infusion of the funny current blocker ZD 7288 (3 ${\mu}mol$/L, n=3), whereas, it was suppressed to 69${\pm}$7 bpm (24% from baseline) by sarcoplasmic reticulum (SR) $Ca^{2+}$ emptying with administering ryanodine (10 ${\mu}mol$/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 $\beta$-adrenergic stimulation, and this interacts synergistically with the voltage clock to increase the heart rate.

Keywords

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