title: Implantation of sinoatrial node cells into canine right ventricle: biological pacing appears limited by the substrate.
abstract: Biological pacing has been proposed as a physiologic counterpart to electronic pacing, and the sinoatrial node (SAN) is the general standard for biological pacemakers. We tested the expression of SAN pacemaker cell activity when implanted autologously in the right ventricle (RV). We  induced complete heart block and implanted electronic pacemakers in the RV of adult mongrel dogs. Autologous SAN cells isolated enzymatically were studied by patch clamp to confirm SAN identity. SAN cells (400,000) were injected into the RV subepicardial free wall and dogs were monitored for  2 weeks. Pacemaker function was assessed by overdrive pacing and IV epinephrine challenge. SAN cells expressed a time-dependent inward current (I(f)) activating on hyperpolarization: density = 4.3 ± 0.6 pA/pF at -105 mV. Four of the six dogs demonstrated >50% of beats  originating from the implant site at 24 h. Biological pacemaker rates on days 7-14 = 45-55 bpm and post-overdrive escape times = 1.5-2.5 s. Brisk catecholamine responsiveness occurred. Dogs implanted with autologous SAN cells manifest biological pacing properties dissimilar  from those of the anatomic SAN. This highlights the importance of cell and substrate interaction in generating biological pacemaker function.
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: David H
authors.initials: DH
authors.lastname: Lau
authors.forename: Iryna N
authors.initials: IN
authors.lastname: Shlapakova
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Peter
authors.initials: P
authors.lastname: Danilo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Robinson
authors.forename: Ira S
authors.initials: IS
authors.lastname: Cohen
authors.forename: Dan
authors.initials: D
authors.lastname: Qu
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Xu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004285:Dogs; D004562:Electrocardiography; D004837:Epinephrine / Q000494:pharmacology; D006327:Heart Block / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D018408:Patch-Clamp Techniques; D012849:Sinoatrial Node / Q000166:cytology / Q000637:transplantation*; D014182:Transplantation, Autologous
chemical_list: D004837:Epinephrine