title: Long-term modulation of the intrinsic cardiac nervous system by spinal cord neurons in normal and ischaemic hearts.
abstract: Electrical excitation of the dorsal aspect of the rostral thoracic spinal cord imparts long-term therapeutic benefits to patients with angina pectoris. Such spinal cord stimulation also induces short-term suppressor effects on the intrinsic cardiac nervous system. The purpose of this study was to determine whether spinal cord stimulation (SCS) induces long-term effects on the intrinsic nervous system, particularly in the presence of myocardial ischaemia. The activity generated by right atrial neurons was recorded in 10 anesthetized dogs during basal states, during prolonged (15 min) occlusion of the left anterior descending coronary artery, and during the subsequent reperfusion phase. Neuronal activity and cardiovascular indices were also monitored when the dorsal T1-T4 segments of the spinal cord were stimulated electrically (50 Hz; 0.2 ms) at an intensity 90% of motor threshold (mean 0.32 mA) for 17 min. SCS was performed before, during and after 15-min periods of regional ventricular ischaemia. Occlusion of a major coronary artery, one that did not perfuse investigated neurons, resulted in their excitation. Ischaemia-induced neuronal excitatory effects were suppressed (-76% from baseline) by SCS. SCS suppression of intrinsic cardiac neuronal activity persisted during the subsequent reperfusion period; after terminating 17 min of SCS, at least 20 min elapsed before intrinsic cardiac neuronal activity returned to baseline values. It is concluded that populations of intrinsic cardiac neurons are activated by inputs arising from the ischaemic myocardium. Ischaemia-induced activation of these neurons is nullified by SCS. The neuronal suppressor effects that SCS induces persist not only during reperfusion, but also for an extended period of time thereafter. These long-term effects may account, in part, for the fact that SCS imparts clinical benefit to patients with angina of cardiac origin not only during its application, but also for a time thereafter.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada. jarmour@is.dal.ca
authors.forename: J A
authors.initials: JA
authors.lastname: Armour
authors.forename: B
authors.initials: B
authors.lastname: Linderoth
authors.forename: R C
authors.initials: RC
authors.lastname: Arora
authors.forename: M J L
authors.initials: MJ
authors.lastname: DeJongste
authors.forename: J L
authors.initials: JL
authors.lastname: Ardell
authors.forename: J G
authors.initials: JG
authors.lastname: Kingma
authors.forename: M
authors.initials: M
authors.lastname: Hill
authors.forename: R D
authors.initials: RD
authors.lastname: Foreman
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000787:Angina Pectoris / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D023921:Coronary Stenosis / Q000503:physiopathology; D004285:Dogs; D004525:Efferent Pathways / Q000502:physiology*; D004599:Electric Stimulation Therapy; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D009474:Neurons / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D014701:Veratridine / Q000494:pharmacology; D017833:Visceral Afferents / Q000187:drug effects / Q000502:physiology
chemical_list: D014701:Veratridine