Regional Cardiac Sympathetic Innervation Early and Late after Transmyocardial Laser Revascularization

G. Chad Hughes, Dmitri V. Baklanov, Shankha S. Biswas, Anne M. Pippen, Timothy R DeGrado, R. Edward Coleman, Carolyn K. Landolfo, James E. Lowe, Brian H. Annex, Kevin P. Landolfo

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalJournal of Cardiac Surgery
Volume19
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

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Transmyocardial Laser Revascularization
Tyrosine 3-Monooxygenase
Myocardium
Septum of Brain
Denervation
Immunoblotting
Lasers
Swine
Holmium
Immunohistochemistry
Staining and Labeling
Sympathectomy
Solid-State Lasers
Thoracotomy
Carbon Dioxide
Action Potentials
Analysis of Variance
Western Blotting
Weights and Measures

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Regional Cardiac Sympathetic Innervation Early and Late after Transmyocardial Laser Revascularization. / Hughes, G. Chad; Baklanov, Dmitri V.; Biswas, Shankha S.; Pippen, Anne M.; DeGrado, Timothy R; Coleman, R. Edward; Landolfo, Carolyn K.; Lowe, James E.; Annex, Brian H.; Landolfo, Kevin P.

In: Journal of Cardiac Surgery, Vol. 19, No. 1, 01.2004, p. 21-27.

Research output: Contribution to journalArticle

Hughes, GC, Baklanov, DV, Biswas, SS, Pippen, AM, DeGrado, TR, Coleman, RE, Landolfo, CK, Lowe, JE, Annex, BH & Landolfo, KP 2004, 'Regional Cardiac Sympathetic Innervation Early and Late after Transmyocardial Laser Revascularization', Journal of Cardiac Surgery, vol. 19, no. 1, pp. 21-27. https://doi.org/10.1111/j.0886-0440.2004.04005.x
Hughes, G. Chad ; Baklanov, Dmitri V. ; Biswas, Shankha S. ; Pippen, Anne M. ; DeGrado, Timothy R ; Coleman, R. Edward ; Landolfo, Carolyn K. ; Lowe, James E. ; Annex, Brian H. ; Landolfo, Kevin P. / Regional Cardiac Sympathetic Innervation Early and Late after Transmyocardial Laser Revascularization. In: Journal of Cardiac Surgery. 2004 ; Vol. 19, No. 1. pp. 21-27.
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T1 - Regional Cardiac Sympathetic Innervation Early and Late after Transmyocardial Laser Revascularization

AU - Hughes, G. Chad

AU - Baklanov, Dmitri V.

AU - Biswas, Shankha S.

AU - Pippen, Anne M.

AU - DeGrado, Timothy R

AU - Coleman, R. Edward

AU - Landolfo, Carolyn K.

AU - Lowe, James E.

AU - Annex, Brian H.

AU - Landolfo, Kevin P.

PY - 2004/1

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N2 - 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.

AB - 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.

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