title: Regional cardiac sympathetic innervation early and late after transmyocardial laser revascularization.
abstract: BACKGROUND
  Prior experimental and clinical studies have drawn disparate conclusions regarding the effects of transmyocardial laser revascularization (TMR) on regional cardiac innervation in the treated regions. Regional afferent denervation has been proposed as a potential mechanism of action of the procedure, although this as yet remains unproven. The purpose of the present study was to evaluate regional myocardial sympathetic innervation both early (3 days) and late (6 months) after TMR.
  
  
  METHODS
  Mini-swine in the early group were randomized to be sacrificed 3 days after holmium:YAG TMR (n = 5) or sham thoractomy (n = 3). In the late group, mini-swine with hibernating myocardium in the left circumflex (LCx) region were randomized to sham redo-thoracotomy (n = 5), TMR of the LCx distribution with a carbon dioxide (n = 5), holmium:YAG (n = 5), or excimer (n = 5) laser. Six months postoperatively the animals were sacrificed. Additional animals in both the early (n = 2) and late (n = 2) groups served as age- and weight-matched normal controls. Immunohistochemistry and Western blot analysis for tyrosine hydroxylase (TYR-OH), a neural-specific enzyme found in sympathetic efferent nerves and a commonly used anatomic marker of regional innervation, were performed on lased and nonlased LCx and septal regions.
  
  
  RESULTS
  Immunohistochemical staining for TYR-OH was markedly diminished in the lased myocardial regions 3 days after TMR. This staining was significantly reduced compared to untreated septal regions, sham-operated, and normal LCx myocardium. Quantitative immunoblotting confirmed a significant reduction in TYR-OH (p < 0.05) protein concentration in the lased regions 3 days after TMR. On the contrary, TYR-OH staining was present in LCx myocardium surrounding the laser channels of all animals in all groups 6 months postoperatively. Staining was not different from controls. Similarly, there was no difference in LCx TYR-OH protein concentration between the normal, sham, or 6 months postoperative lased groups (p > 0.2 by one-way ANOVA).
  
  
  CONCLUSIONS
  TMR-treated myocardium demonstrates anatomic evidence of regional sympathetic denervation 3 days postoperatively, although myocardium lased with each of the three lasers currently in clinical use is reinnervated by 6 months as evidenced by immunoblotting and immunohistochemistry for TYR-OH. These results suggest that mechanisms other than denervation may account for the long-term reductions in angina seen after TMR.
authors.affiliation: Division of Cardiovascular Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. chadh@duke.edu
authors.forename: G Chad
authors.initials: GC
authors.lastname: Hughes
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Baklanov
authors.forename: Shankha S
authors.initials: SS
authors.lastname: Biswas
authors.forename: Anne M
authors.initials: AM
authors.lastname: Pippen
authors.forename: Timothy R
authors.initials: TR
authors.lastname: DeGrado
authors.forename: R Edward
authors.initials: RE
authors.lastname: Coleman
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Landolfo
authors.forename: James E
authors.initials: JE
authors.lastname: Lowe
authors.forename: Brian H
authors.initials: BH
authors.lastname: Annex
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Landolfo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D015153:Blotting, Western; D003327:Coronary Disease / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D006321:Heart / Q000294:innervation*; D007150:Immunohistochemistry; D053685:Laser Therapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009204:Myocardial Revascularization / Q000009:adverse effects / Q000379:methods*; D009416:Nerve Regeneration / Q000502:physiology*; D011336:Probability; D011897:Random Allocation; D020127:Recovery of Function; D012680:Sensitivity and Specificity; D013556:Swine, Miniature; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology; D013997:Time Factors