THE EFFECTS OF RECOMBINANT HUMAN HEMOGLOBIN ON ESOPHAGEAL MOTOR FUNCTION IN HUMANS

Background & Aims: Nitric oxide controls lower esophageal sphincter (L ES) relaxation and esophageal peristalsis in opossums, but its role in the control of esophageal motility in humans is not defined. Hemoglob in inactivates NO by binding it. Recombinant human hemoglobin (rHb1.1) was used to test the hypothesis that NO mediates esophageal motor fun ctions in humans. Methods: rHb1.1 or human serum albumin was administe red intravenously to fasting male volunteers. Esophageal manometric st udies were performed before, during, and up to 6 hours after the infus ion. Results: rHb1.1 increased the velocities of peristaltic contracti ons to produce simultaneous contractions in 6 of 9 subjects. It increa sed 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 con tractions occurred in 8 of 9 subjects. Lower retrosternal chest pain d uring swallowing was observed in 4 subjects. Conclusions: rHb1.1 inter fered with esophageal peristalsis and LES relaxation. It precipitated esophageal spasm in some subjects. These data support the hypothesis t hat the timing of smooth muscle esophageal peristalsis and LES relaxat ion are mediated by NO. They suggest that some disorders of esophageal motor function may result from defects in NO neuromuscular communicat ion.