Effect of parasympathetic blockade on ventilatory and cardiac depression induced by opioids

Gabriel G. Haddad, Patrick A. Lasala

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We have previously shown that delta-opioid agonists decrease ventilation and heart rate. Because of these results and the known interactions between opioid and acetylcholine metabolism, we hypothesized that opioids induce cardiorespiratory changes via the parasympathetic nervous system. To test this hypothesis, we administered atropine sulfate (systematically) at maximal effect of d-Ala-d-Leu-enkephalin (DADLE; a preferential delta-opioid agonist), injected intracisternally, and examined its effect on cardiorespiratory function. All experiments were performed on chronically instrumented and conscious adult dogs. Mean instantaneous minute ventilation or Vt/Ttot decreased and PaCO2 increased after DADLE; atropine had little effect on these changes. Naloxone, even in small doses, reversed opioid effects on Vt/Ttot and PaCO2. Atropine, however, reversed the DADLE-induced depression in cardiac rate. In doses that reversed this cardiac depression, atropine had no effect on cardiorespiratory function at rest, i.e., with no prior administration of DADLE. We conclude that DADLE (1) decreases heart rate by increasing parasympathetic activity to the heart and (2) induces hypoventilation by a different mechanism. We speculate that the opioid-induced ventilatory depression is due to either (a) direct opioid action on central respiratory regulation or (b) parasympathetic non-muscarinic or non-cholinergic mediating mechanisms.

Original languageEnglish (US)
Pages (from-to)101-114
Number of pages14
JournalRespiration Physiology
Volume67
Issue number1
DOIs
StatePublished - Jan 1987
Externally publishedYes

    Fingerprint

Keywords

  • Acetylcholine
  • Cardiorespiratory regulatory centers
  • Dog
  • Heart rate
  • Opioids
  • Ventilation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this