Abstract 18009: Chronic Spinal Cord Stimulation Preserves Cardiac Sympathetic Responses and Normalizes Noradrenergic Gene Expression in Stellate Ganglion in a Canine Heart Failure Model
Background: Myocardial infarction (MI) leads to adverse remodeling of the heart and cardiac neuronal hierarchy, both contributing to the development of heart failure (HF). Our previous work demonstrated that thoracic spinal cord stimulation (SCS) improved parasympathetic efferent function and survival in a canine model of HF induced by MI and mitral regurgitation (MR). The objective of this study was to determine whether SCS also had beneficial effects on the sympathetic element of the cardiac neuronal hierarchy.
Methods: A HF model was created in 15 canines by performing sequential surgeries to generate MI and then MR. SCS electrodes and generators were implanted during the first surgery. Seven of the MI/MR animals received SCS (T1-T5; 20 Hz, 200 μsec, 90% of motor threshold) starting one week after MR induction. Generators were not activated in the sham SCS group (n=8). Canines were anesthetized for terminal experiments to record cardiac responses to stellate ganglion stimulation and then to collect the stellate ganglia for RNA analysis by Q-PCR.
Results: MI/MR blunted the chronotropic and inotropic responses to stimulation of the right or left stellate ganglia. Treatment with reactive SCS significantly improved functional responses to right or left stellate stimulation. For example, right stellate stimulation evoked the following percent changes in sham SCS vs SCS: Cardiac output, 20.6±3.8 vs 66.2±9.2; LV +dp/dt, 38.3±10.2 vs 112.8±13.1; and LV -dp/dt, 13.8±8.3 vs 72.6±12.1 (P<0.05 for all). RNA analysis of stellate ganglia showed that the sham SCS group had significantly increased expression of tyrosine hydroxylase and vesicular monoamine transporter 2 and decreased expression of α2 adrenergic receptor mRNA compared to the SCS treatment group and an acute control group (n=8).
Conclusion: Chronic MI/MR results in impaired functional sympathetic control of cardiac function and corresponding molecular changes in the stellate ganglion reflective of excessive and adverse sympathetic activation. Therapeutic SCS ameliorates adverse changes in sympathetic function and gene expression in canines with MI/MR.
- Autonomic nervous system
- Central nervous system
- Systems physiology
- Reflexes, cardiovascular
- © 2013 by American Heart Association, Inc.