Effect of an o‐raffinose cross‐linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function

Abstract

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effects on oesophageal motility of an o-raffinose cross-linked haemoglobin-based oxygen carrier (HBOC) purified from outdated donated human blood cells (HemolinkTM), with attention to dose-response (0.6-2.4 g kg-1), oxygenation status and low molecular weight components (4.4-36.4% 64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.

Artificial Oxygen Carriers as Red Blood Cell Substitutes: A Selected Review and Current Status

“…In some animal models, increased esophageal peristaltic velocity, decreased lower esophageal sphincter relaxation, increased jejunal tone, and phasic contraction were observed. These effects were reversed by calcium‐channel blocker (74,75). NO release from the myenteric neurons of the esophageal smooth muscle is believed to be a primary factor for the relaxation of the lower esophageal sphincter and peristaltic latency in response to swallowing (72).…”

Hemolink™-Induced Effects on Intestinal Motor Function and Attenuation of These Effects by Selected Agents

“…HemolinkTM, a human hemoglobin solution crosslinked and oligomerized with periodate ring-opened raffinose, has been shown to inhibit lower-esophageal sphincter (LES) relaxation, and to increase esophageal peristaltic velocity, in both the cat and the opossum (1). Similar esophageal motility effects have also been reported with other hemoglobin-based oxygen carriers (HBOC) currently under development in both animals and humans (2-5).…”