This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Arora, R. C. Articles by Armour, J. A. Search for Related Content PubMed PubMed Citation Articles by Arora, R. C. Articles by Armour, J. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB PHENOL VERATRIDINE Related Collections Animal models of human disease Other Treatment CV surgery: other

(Circulation. 2001;104:I-115.)
© 2001 American Heart Association, Inc.

Surgery for Congenital Heart Disease

Transmyocardial Laser Revascularization Remodels the Intrinsic Cardiac Nervous System in a Chronic Setting

R. C. Arora, MD; G. M. Hirsch, MD; K. Hirsch, MD; J. A. Armour, MD, PhD

From the Departments of Surgery (R.C.A., G.M.H.), Anesthesiology (K.H.), and Physiology and Biophysics (J.A.A.), Dalhousie University, Halifax, Nova Scotia, Canada.

Correspondence to Dr R.C. Arora, 1796 Summer St, Room 2269, QEII HSC–NHI Site, Halifax, Nova Scotia B3H 3A7. E-mail rca72{at}hotmail.com

Background— Prospective trials have demonstrated that transmyocardial laser revascularization (TMLR) imparts symptomatic relief to patients with refractory angina. Because peak clinical effectiveness of TMLR is usually delayed by several months, it has been proposed that ventricular denervation is one mechanism whereby TMLR imparts symptomatic relief. We have demonstrated that TMLR does not denervate the heart in the acute setting, nor does it modify the intrinsic cardiac nervous system (ICNS) in the acute setting. However, the long-term effects of TMLR on the ICNS remain unknown.

Methods and Results— A holmium:yttrium-aluminum-garnet laser created 20 channels through the anterolateral left ventricular free wall of 10 dogs. Four weeks later, the function of cardiac sensory inputs to the ICNS was studied by applying veratridine (7.5 µmol/L) to ventricular sensory fields. Chronotropic and inotropic responses elicited by cardiac sympathetic or parasympathetic efferent neurons stimulated electrically (10 Hz, 4 V, 4 ms) or chemically (nicotine 5 to 20 µg/kg IV) were also assessed. Chemical activation of epicardial sensory neurites with veratridine elicited expected ICNS excitatory responses. Electrical stimulation of sympathetic and parasympathetic efferent neurons induced expected altered cardiac responses. In contrast, the responsiveness of the ICNS to systemically administered nicotine was obtunded.

Conclusions— Although chronic TMLR does not affect cardiac afferent or extracardiac efferent neuronal function, it does "remodel" the ICNS so that its responsiveness to a known potent chemical agonist (ie, nicotine) becomes obtunded. Remodeling of the ICNS may account in part for the delayed symptomatic relief that TMLR imparts to patients with refractory angina.

Key Words: nervous system, autonomic • angiotensin • conduction • contractility