title: Hemolink-induced effects on intestinal motor function and attenuation of these effects by selected agents.
abstract: Hemolink, an oxidized, ring-opened raffinose-crosslinked hemoglobin-based oxygen carrier produced by Hemosol Inc., stimulates esophageal peristalsis, possibly by interference with neural NO-mediated effects. The effects of Hemolink on jejunal tone and contractions, arterial pressure and heart rate were measured in anesthetized rats, and the effect of selected agents in attenuating or reversing these effects was studied. Infusion of L-NAME was used to validate the study model; it caused an immediate increase in tone and initiated phasic contractions indicating that the model was responsive to NO-mediated effects. Hemolink administration caused effects on intestinal motor function similar to those caused by L-NAME, including increases in basal tone and contraction amplitude. Rat whole blood caused none of these changes. The Hemolink-induced effects were less immediate in some animals compared to those observed after L-NAME. As well there was greater inter-animal variability on the effects. Hemolink administration also caused a mild increase in arterial blood pressure and a reciprocal decrease in heart rate in some animals. Co-administration of morphine, a common analgesic that has been reported to influence the motility of the GI tract; L-arginine, a substrate for NO synthesis; and glycopyrrolate, an anti-cholinergic agent, did not significantly modulate the Hemolink effects, whereas nitroglycerin, an NO donor; and nifedipine, a slow calcium-channel blocker, attenuated or reversed these effects.
authors.affiliation: Hemosol Inc., Etobicoke, Ontario, Canada.
authors.forename: L T
authors.initials: LT
authors.lastname: Wong
authors.forename: S S
authors.initials: SS
authors.lastname: Er
authors.forename: J
authors.initials: J
authors.lastname: Ning
authors.forename: B
authors.initials: B
authors.lastname: Christoff
authors.forename: F J
authors.initials: FJ
authors.lastname: Carmichael
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006024:Glycopyrrolate / Q000008:administration & dosage; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009543:Nifedipine / Q000008:administration & dosage; D005996:Nitroglycerin / Q000008:administration & dosage; D011887:Raffinose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000701:Analgesics, Opioid; D006454:Hemoglobins; C097124:O-raffinose cross-linked human hemoglobin; D009020:Morphine; D001120:Arginine; D005996:Nitroglycerin; D009543:Nifedipine; D011887:Raffinose; D006024:Glycopyrrolate