title: Autonomic control of heart rate in dogs treated chronically with morphine.
abstract: The vagotonic effect of chronic morphine on the parasympathetic control of the heart was examined in dogs treated with morphine for 2 wk. Because normal vagal function is critical to myocardial stability, the study was conducted to evaluate for potential impairments following chronic vagal stimulation. The hypothesis that persistent vagal outflow would result in a loss of vagal reserve and reduced vagal control of heart rate was tested. Heart rate and the high-frequency variation in heart rate (power spectral analysis) declined shortly after initiation of subcutaneous morphine infusion. A progressive bradycardia correlated well with the rising plasma morphine. The resting bradycardia (57 beats/min) was maintained through day 2 and was accompanied by a significant parallel increase in vagal effect and a decline in the intrinsic heart rate (160 vs. 182 beats/min). A compensatory increase in the ambient sympathetic control of heart rate was evident on day 2 and was supported by an increase in circulating catecholamines. The lowered intrinsic heart rate and elevated sympathetic activity were maintained through day 10 despite a return of the resting heart rate and plasma catecholamines to pretreatment values. These observations suggested that chronic morphine alters either the intrinsic function of the sinoatrial node or reduces the postvagal tachycardia normally attributed to nonadrenergic, noncholinergic agents. Both acute and chronic morphine depressed the rate of development of bradycardia during direct vagal nerve stimulation without altering the rate of recovery afterward. This last observation suggests that acute morphine reduces the rate of acetylcholine release. Results provide insight into the mechanisms that maintain vagal responsiveness. The results are also relevant clinically because opiates are increasingly prescribed for chronic pain and opiate abuse is currently in resurgence.
authors.affiliation: Department of Integrative Physiology and the Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Napier
authors.forename: A
authors.initials: A
authors.lastname: Stanfill
authors.forename: D A
authors.initials: DA
authors.lastname: Yoshishige
authors.forename: K E
authors.initials: KE
authors.lastname: Jackson
authors.forename: B A
authors.initials: BA
authors.lastname: Barron
authors.forename: J L
authors.initials: JL
authors.lastname: Caffrey
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D009294:Narcotics; D009020:Morphine; D009638:Norepinephrine; D004837:Epinephrine