Abstract:
Background: Nitric oxide (NO) has been showed to modulate esophageal peristalsis contractions in healthy humans. Objective: To study if isosorbide dinitrate (ISDN) which is exogenous NO donor can restore esophageal peristalsis contractions in symptomatic patients with distal esophageal spasm. Methods: Ten patients were randomized to undergo high resolution manometry (HRM) with ISDN spray (1.25 mg/puff) or normal saline (NSS) spray, in 2 times at least 48 hours apart, in crossover randomized controlled trial (assessor blind). For each HRM study, esophageal contractions in response to 12 wet swallows were studied at baseline, after the first 1-puff and the second 1-puff of test agents. Results: Prevalence of esophageal peristalsis contractions was similar at baseline (p>0.05) and increased by ISDN significantly only after the first dose (65% vs. 50%, p =0.045) but not the second dose compared to NSS (p >0.05). ISDN decreased DCI after the first dose (1421±839 vs. 2363±1581 mmHg s⁻¹cm⁻¹, p =0.050) and significantly decreased after the second dose (1399±739 vs. 2409±1289 mmHg s⁻¹cm⁻¹, p =0.006) compared to NSS. ISDN significantly increased residual UES relaxation pressure after the first dose (0.5±3.7 vs. -4.0±6.2 mmHg, p =0.026) and the second dose (1.2±4.5 vs.-3.9±6.5 mmHg, p =0.027) compared to NSS. However, there was no significant difference of PFV, 4-second IRP and UES resting pressure comparing between ISDN and NSS at baseline, after the first dose and the second dose of the test agents (p >0.05). Conclusion: In patients with distal esophageal spasm, proportion of esophageal peristalsis contraction was increased overtime after HRM catheter insertion. ISDN significantly improved peristalsis contractions earlier than NSS, decreased DCI or force of contractions, and increased residual UES relaxation pressure. This study suggests the role of central nervous system or esophageal adaptation to local stimulus and exogenous NO on the restoration of esophageal peristalsis contractions.