Cardiac Parasympathetic Dysfunction in Morphine Addiction

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dc.contributor.advisorCaffrey, James L.
dc.contributor.committeeMemberRaven, Peter B.
dc.contributor.committeeMemberGwirtz, Patricia A.
dc.creatorNapier, Leslie D.
dc.date.accessioned2019-08-22T21:08:32Z
dc.date.available2019-08-22T21:08:32Z
dc.date.issued1997-12-01
dc.date.submitted2013-10-23T07:50:06-07:00
dc.description.abstractNapier, Leslie D., Cardiac Parasympathetic Dysfunction in Morphine Addiction. Doctor of Philosophy (Biomedical Sciences), December, 1997, 137 pp., 9 tables, 22 figures, references, 163 titles. The effects of chronic morphine treatment on parasympathetic control of the heart and associated cellular mechanisms were examined using a canine model. Vagal bradycardia was significantly blunted in dogs treated for one week with subcutaneous morphine pellets. In a separate group of dogs, heart rate and high frequency fluctuations in heart rate declined during the first three hours of subcutaneous morphine infusion consistent with the vagatonic action of acute morphine. Heart rate remained below baseline on Day 2 of the morphine infusion but had returned to normal by Day 10. Ambient sympathetic tone was increased on Days 2 and 10, and plasma catecholamines were elevated on Day 2. The intrinsic heart rates on Days 2 (160 bpm) and 10 (162 bpm) of morphine treatment were lower than the pre-treatment rate (182 bpm). Suggested mechanisms include a fundamental change in sinoatrial nodal cell function or attenuated tachycardia induced by vasoactive intestinal peptide co-released with acetylcholine from post-ganglionic parasympathetic neurons. The time to 50% maximal bradycardia during vagal nerve stimulation was increased with chronic and acute morphine suggesting an effect on the rate of acetylcholine synthesis, release or degradation. Muscarinic receptor density in left ventricular and right atrial sarcolemmal membranes from dogs treated chronically with morphine were 34% and 17% higher, respectively, than in control animals. Chronic morphine had no effect on basal or MnCl2-stimulated cyclase activity in either region. Similarly, maximal β-adrenergic and muscarinic receptor/G-protein coupling to adenylate cyclase were not altered by chronic morphine. Atrial norepinephrine content was higher than that in the ventricles and was unaltered by morphine. Ventricular norepinephrine was decreased with chronic but not acute morphine treatment. Epinephrine was evenly distributed throughout the myocardium and was reduced in both the atria and the ventricles by either acute or chronic morphine. This pattern suggests that morphine may reduce extraneuronal uptake of catecholamines. Collectively these studies show that chronic morphine treatment and the accompanying persistent vagal activity may reduce parasympathetic function. This attenuated function, however, is short-lived since sympathetic systems adapt with compensatory responses masking, or perhaps reversing, initial parasympathetic deficits.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29102
dc.language.isoen
dc.provenance.legacyDownloads17
dc.subjectCardiovascular System
dc.subjectChemicals and Drugs
dc.subjectCirculatory and Respiratory Physiology
dc.subjectComparative and Laboratory Animal Medicine
dc.subjectLife Sciences
dc.subjectMedical Toxicology
dc.subjectMedicine and Health Sciences
dc.subjectOther Pharmacy and Pharmaceutical Sciences
dc.subjectPharmacy and Pharmaceutical Sciences
dc.subjectSubstance Abuse and Addiction
dc.subjectCardiac parasympathetic dysfunction
dc.subjectmorphine addiction
dc.subjectvagal bradycardia
dc.subjectdogs
dc.subjectheart rate
dc.subjectnerve stimulation
dc.subjectextraneuronal uptake of catecholamines
dc.subjectparasympathetic function
dc.titleCardiac Parasympathetic Dysfunction in Morphine Addiction
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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