Effect of an o-raffinose cross-linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function.
The present experiments evaluate the effects on oesophageal motility of an o-raffinose cross-linked haemoglobin-based oxygen carrier (HBOC) purified from outdated donated human blood cells (HemolinkTM), with attention to dose-response (0.6-2.4 g kg-1), oxygenation status and low molecular weight components (4.4-36.4% 64 kDa or less). In ketamine-anaesthetized cats, lower oesophageal sphincter (LES) function and oesophageal peristalsis were monitored 0.5 h before, during and up to 3.5 h after HBOC infusion, and in some cats at 24 h. (1) All products significantly inhibited LES relaxation and increased peristaltic velocity in the distal smooth muscle oesophagus, without consistently altering resting LES pressure. (2) Effects on peristaltic velocity reached a maximum at the smallest dose, whereas the effects on LES relaxation had a maximum effect at 1.2 g kg-1. (3) Effects were not significantly altered by the haemoglobin oxygenation status or presence of low molecular weight components. (4) Repetitive oesophageal contractions occurred. In the cat, an o-raffinose cross-linked human haemoglobin product produces changes in oesophageal body and LES function, which are independent of the HBOC oxygenation status and composition of the low molecular weight components tested. Changes may persist for at least 24 h. These motility changes are likely due to scavenging of nitric oxide by the haemoglobin.
Xue
S
S
University of Toronto, Ontario, Canada.
Paterson
W
W
Valdez
D
D
Miller
D
D
Christoff
B
B
Wong
L T
LT
Diamant
N E
NE
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D003432:Cross-Linking Reagents; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects*; D004947:Esophagus / Q000187:drug effects*; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010528:Peristalsis / Q000187:drug effects; D011887:Raffinose / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D003432:Cross-Linking Reagents; D006454:Hemoglobins; D018727:Muscarinic Antagonists; C097124:O-raffinose cross-linked human hemoglobin; D001285:Atropine; D011887:Raffinose