title: Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology.
abstract: OBJECTIVE
  The purpose of this study was to better understand the effects of long-term right ventricular pacing on left ventricular perfusion, innervation, function and histology.
  
  
  BACKGROUND
  Long-term right ventricular apical pacing is associated with increased congestive heart failure and mortality compared with atrial pacing. The exact mechanism for these changes is unknown. In this study, left ventricular perfusion, sympathetic innervation, function and histologic appearance after long-term pacing were studied in dogs in an attempt to see whether basic changes might be present that might ultimately be associated with the adverse clinical outcome.
  
  
  METHODS
  A total of 24 dogs were studied. Sixteen underwent radiofrequency ablation of the atrioventricular (AV) junction to produce complete AV block. Seven of these underwent long-term pacing from the right ventricular apex (ventricular paced group), and nine had atrial and right ventricular apical pacing with AV synchrony (dual-chamber paced group). A control group of eight dogs had sham ablations with normal AV conduction. These dogs had atrial pacing only. Regional perfusion and sympathetic innervation were studied in all dogs by imaging with thallium-201 and [I123]metaiodobenzylguanidine, respectively. The degree of innervation was also determined by assay of tissue norepinephrine levels. Left ventricular function was assessed by radionuclide ventriculography. Cardiac histology was studied with both light and electron microscopy.
  
  
  RESULTS
  Mismatching of perfusion and innervation in the ventricular paced group was noted, with perfusion abnormalities of both the septum and free wall. Regional [I123]metaiodobenzylguanidine distribution was homogeneous. Tissue norepinephrine levels were elevated in both the ventricular and dual-chamber paced groups compared with the control group. No light or electron microscopic findings were noted in any groups. In the dual-chamber paced group, diastolic dysfunction was noted, with normal systolic function.
  
  
  CONCLUSIONS
  Ventricular pacing resulted in regional changes in tissue perfusion and heterogeneity between perfusion and sympathetic innervation. Both ventricular and dual-chamber pacing were associated with an increase in tissue catecholamine activity. The abnormal activation of the ventricles via right ventricular apical pacing may result in multiple abnormalities of cardiac function, which may ultimately affect clinical outcome.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143-1354.
authors.forename: M A
authors.initials: MA
authors.lastname: Lee
authors.forename: M W
authors.initials: MW
authors.lastname: Dae
authors.forename: J J
authors.initials: JJ
authors.lastname: Langberg
authors.forename: J C
authors.initials: JC
authors.lastname: Griffin
authors.forename: M C
authors.initials: MC
authors.lastname: Chin
authors.forename: W E
authors.initials: WE
authors.lastname: Finkbeiner
authors.forename: J W
authors.initials: JW
authors.lastname: O'Connell
authors.forename: E
authors.initials: E
authors.lastname: Botvinick
authors.forename: M M
authors.initials: MM
authors.lastname: Scheinman
authors.forename: M
authors.initials: M
authors.lastname: Rosenqvist
mesh_terms: D019797:3-Iodobenzylguanidine; D000818:Animals; D003287:Contrast Media; D004285:Dogs; D005260:Female; D015637:Gated Blood-Pool Imaging; D006327:Heart Block / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000294:innervation / Q000503:physiopathology / Q000648:ultrastructure; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D010138:Pacemaker, Artificial; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013794:Thallium Radioisotopes; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D003287:Contrast Media; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D013794:Thallium Radioisotopes; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine