Second-generation recombinant hemoglobin molecules do not stimulate sphincter of Oddi, gallbladder or duodenal motility in the Australian brush-tailed possum.
BACKGROUND
Several studies have investigated the effects of hemoglobin-based oxygen carriers on gastrointestinal motility. Diaspirin cross-linked hemoglobin reduces sphincter of Oddi trans-sphincteric flow and increases duodenal motility in the Australian brush-tailed possum, effects attributed to nitric oxide (NO) scavenging. Recently, second-generation recombinant hemoglobin molecules with reduced NO scavenging ability have been developed.


OBJECTIVE
To determine the effects of two second-generation recombinant hemoglobin solutions and the prototype recombinant hemoglobin with high NO binding, on duodenal and biliary motility in the Australian brush-tailed possum.


METHODS
Blood pressure; duodenal, sphincter of Oddi and gallbladder motility; and trans-sphincteric flow were recorded. The effects of recombinant hemoglobin or human serum albumin (control) solutions on these parameters were investigated. Each solution was infused intravenously at 1 mL/kg/min to deliver 250 mg/kg or 500 mg/kg.


RESULTS
Duodenal contraction frequency was stimulated by the high dose of prototype recombinant hemoglobin, but not by a comparable dose of second-generation recombinant hemoglobin. The induced duodenal activity occurred in the later phase of the experimental period. In contrast, biliary motility and trans-sphincteric flow were not altered by any hemoglobin solution. The high dose of all the hemoglobin solutions elevated blood pressure, whereas the low dose solutions did not alter any parameter measured.


CONCLUSIONS
At the doses studied, the second-generation recombinant hemoglobin with reduced NO binding capacity did not significantly alter duodenal and biliary motility, supporting the need for further studies to evaluate their potential usefulness as blood substitutes.
Takahata
Shunichi
S
Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Science, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
Konomi
Hiroyuki
H
Schloithe
Ann C
AC
Toouli
James
J
Saccone
Gino T P
GT
D000818:Animals; D001794:Blood Pressure; D001802:Blood Substitutes; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006455:Hemoglobins, Abnormal / Q000494:pharmacology*; D008297:Male; D009893:Opossums; D011994:Recombinant Proteins / Q000494:pharmacology*; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000502:physiology
D001802:Blood Substitutes; D006455:Hemoglobins, Abnormal; D011994:Recombinant Proteins; C105876:hemoglobin rHb1.1