title: Inotropic effect of meperidine: influence of receptor and ion channel blockers in the rat atrium.
abstract: Meperidine increases developed force in isolated rat atria. We initiated this study to determine if this positive inotropic effect was attenuated by commonly used receptor- and ion channel blockers. Neither naloxone (opioid blocker), phentolamine (alpha-adrenoceptor blocker), propranolol (beta-adrenoceptor blocker), polaramine (H1-receptor blocker), ranitidine (H2-receptor blocker), verapamil (calcium-channel blocker), nor lidocaine (fast sodium-channel blocker) attenuated the positive inotropic effect of meperidine. However, after lidocaine pretreatment meperidine increased contractile force by 57% (27%-80%) (median and 95% confidence interval), which is significantly more (P less than 0.001) than the 21% (13%-35%) increase seen after pretreatment with saline. After Na,K-pump inhibition by ouabain, meperidine caused no further increase in contractility, but the atria still responded to isoproterenol with an increase in developed force. Conversely, meperidine prevented the positive inotropic effect of ouabain. These findings suggest that the positive inotropic effect of meperidine is mediated by an increase in intracellular sodium activity and not by regulation of the slow inward calcium channel.
authors.affiliation: Institute for Experimental Medical Research, Ullevål Hospital, Oslo, Norway.
authors.forename: K G
authors.initials: KG
authors.lastname: Helgesen
authors.forename: O
authors.initials: O
authors.lastname: Ellingsen
authors.forename: A
authors.initials: A
authors.lastname: Ilebekk
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D008614:Meperidine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects; D011968:Receptors, Histamine / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; D011941:Receptors, Adrenergic; D011968:Receptors, Histamine; D015222:Sodium Channels; D010042:Ouabain; D008614:Meperidine; D012964:Sodium