The effects of recombinant human hemoglobin on esophageal motor functions in humans.
OBJECTIVE
Nitric oxide controls lower esophageal sphincter (LES) relaxation and esophageal peristalsis in opossums, but its role in the control of esophageal motility in humans is not defined. Hemoglobin inactivates NO by binding it. Recombinant human hemoglobin (rHb1.1) was used to test the hypothesis that NO mediates esophageal motor functions in humans.


METHODS
rHb1.1 or human serum albumin was administered intravenously to fasting male volunteers. Esophageal manometric studies were performed before, during, and up to 6 hours after the infusion.


RESULTS
rHb1.1 increased the velocities of peristaltic contractions to produce simultaneous contractions in 6 of 9 subjects. It increased the amplitude and duration of contractile waves in the esophagus. There was no consistent effect on the resting tone of the LES, but LES relaxation was inhibited. Spontaneous, simultaneous high-pressure contractions occurred in 8 of 9 subjects. Lower retrosternal chest pain during swallowing was observed in 4 subjects.


CONCLUSIONS
rHb1.1 interfered with esophageal peristalsis and LES relaxation. It precipitated esophageal spasm in some subjects. These data support the hypothesis that the timing of smooth muscle esophageal peristalsis and LES relaxation are mediated by NO. They suggest that some disorders of esophageal motor function may result from defects in NO neuromuscular communication.
Murray
J A
JA
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City VA Medical Center, USA.
Ledlow
A
A
Launspach
J
J
Evans
D
D
Loveday
M
M
Conklin
J L
JL
D000328:Adult; D004943:Esophagogastric Junction / Q000187:drug effects; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology*; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008365:Manometry; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D010528:Peristalsis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
D006454:Hemoglobins; D011994:Recombinant Proteins; D009569:Nitric Oxide