Читать книгу The Esophagus - Группа авторов - Страница 58

Distal esophageal spasm occurs due to impaired inhibitory innervation resulting in premature contractions that may cause symptoms of dysphagia and retrosternal pain [124]. The underlying pathophysiology of DES remains poorly understood. One proposed theory is that patients with DES suffer from malfunctioning endogenous nitric oxide synthesis and/or its degradation [124]. Nitric oxide (NO) and cholinergic neurons mediate smooth muscle contraction. A pilot study by Konteurek et al. treated five patients with esophageal spasm using glyceryl trinitrate (prodrug of nitrous oxide) in increasing doses of L‐arginine (amino acid necessary for nitrous oxide synthesis) on two separate occasions with repeated manometric measurements [144]. Patients treated with glyceryl trinitrate had a notable reduction in the duration of contraction (from 11.2 +/‐ 4.8 sec to 4.4 +/‐ 0.8 sec), while the administration of L‐arginine did not cause any significant alterations in manometric findings. Further supporting this hypothesis, Murray et al. evaluated the role of nitric oxide in asymptomatic, fasting male volunteers randomly assigned to receive intravenous human serum albumin or recombinant human hemoglobin (which inactivates nitrous oxide) [145]. A majority of those who received recombinant human hemoglobin demonstrated increased velocities of peristaltic contractions (p < 0.01), increased amplitude and duration of contractile waves (p < 0.05), and impaired LES relaxations, suggesting that NO mediates the timing of smooth muscle esophageal peristalsis and LES relaxations [145]. Additionally, retrosternal chest pain during swallowing was also seen in four of nine subjects, further supporting a role for DES and NO production in the etiology of ECP. Some experts believe DES to be a precursor to achalasia and thus may share mechanisms by which noncardiac chest pain develops [146, 147]