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

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 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.

DOI: 10.4070/kcj.2011.41.11.658

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@inproceedings{Park2011HeartRA, title={Heart Rate Acceleration of a Subsidiary Pacemaker by β-Adrenergic Stimulation}, author={Sanghoon Park and Hyerim Park and Hye Jin Hwang and Jaemin Shim and Jung-Hoon Sung and Jong Youn Kim and Hui-Nam Pak and Moon-hyoung Lee and Boyoung Joung}, booktitle={Korean circulation journal}, year={2011} }