Influence of sildenafil on esophageal motor function in humans: Studies using high‐resolution manometry

Liu

et al. 2020

Self Cite

Background and Aim Prucalopride, a high‐affinity 5‐hydroxytryptamine 4 receptor agonist, promotes esophageal peristalsis, while phosphodiesterase type 5 inhibitor sildenafil inhibits esophageal peristalsis. The present study was aimed to evaluate whether prucalopride would augment esophageal peristalsis subsequent to the application of sildenafil. Methods Seventeen healthy adults underwent high‐resolution manometry by a catheter with one injection port located in the mid‐esophagus. Secondary peristalsis was assessed by rapid air injections after water swallows. Two sessions were randomly performed including acute administration of sildenafil 50 mg after pretreatment with prucalopride or the placebo. Results The frequency of primary peristalsis subsequent to the administration of sildenafil was significantly increased by prucalopride (P = 0.02). Prucalopride also significantly increased distal contractile integral of primary peristalsis subsequent to the administration of sildenafil (P = 0.03). No difference in the frequency of secondary peristalsis subsequent to the administration of sildenafil for air injects of 10 mL (P = 0.14) or 20 mL (P = 0.21) was found between prucalopride and placebo. Prucalopride did not change distal contractile integral of secondary peristalsis subsequent to the administration of sildenafil for air injections of 10 mL (P = 0.09) or 20 mL (P = 0.12). Conclusions Prucalopride modulates sildenafil‐induced inhibition of primary peristalsis by increasing its effectiveness and peristaltic wave amplitude. Our findings suggest that activation of 5‐hydroxytryptamine 4 receptors plays a role in mediating sildenafil‐induced inhibition of esophageal primary peristalsis rather than secondary peristalsis.

Section: Discussionsupporting

confidence: 69%

“…It can be used for patients with spastic esophageal motor disorders 20,21 . By using high‐resolution manometry (HRM), sildenafil was shown to inhibit primary and secondary peristalsis in healthy adults 22,23 …”

Section: Introductionmentioning

confidence: 99%

Effect of prucalopride on sildenafil‐induced inhibition of esophageal peristalsis in healthy adults

Liu

et al. 2020

Self Cite

“…Previous study conducted involving conventional manometry has suggested that sildenafil reduces the amplitude of primary peristalsis 12 . Recent study utilizing HRM has demonstrated that sildenafil inhibits both esophageal body contractility and contraction reserve when compared with placebo 19 . Our study appears to be the first to address the impact of sildenafil on secondary peristalsis using HRM.…”

Section: Discussionmentioning

confidence: 76%

“…The catheter was positioned with the most distal sensor located in the LES high‐pressure zone. We chose a dose of 50 mg of sildenafil and performed HRM study 1 h after drug administration according to previous studies investigating effects of sildenafil on esophageal motility 12,19 …”

Section: Methodsmentioning

confidence: 99%

Effects of phosphodiesterase‐5 inhibitor sildenafil on esophageal secondary peristalsis: Studies with high‐resolution manometry

Liu

et al. 2020

Self Cite

Background and Aim Secondary peristalsis contributes to the clearance of retained refluxate from the esophagus. Sildenafil, a phosphodiesterase‐5 inhibitor, inhibits primary esophageal peristalsis, but its effects on secondary peristalsis remain unknown. This study sought to investigate whether sildenafil could influence physiological characteristics of secondary peristalsis by applying high‐resolution manometry (HRM). Methods Seventeen healthy volunteers (15 men and 2 women, aged 30.2 ± 6.4 years) underwent two HRM studies on separate days following the administration of either a placebo or 50 mg of sildenafil in a random order. Both studies were performed using a water‐perfused HRM catheter containing one air injection channel positioned in the mid‐esophagus. Secondary peristalsis was stimulated by a rapid mid‐esophageal injection of 10 or 20 mL of air 1 h after the administration of either the placebo or sildenafil. The frequency and distal contractile integral of secondary peristalsis were then compared. Results Complete secondary peristalsis triggered by the 20‐mL air injection was more frequent than observed with the 10‐mL air injection (P < 0.001). The vigor of secondary peristalsis triggered by the injection of either volume of air was lower than that of primary peristalsis (P < 0.001). Sildenafil significantly reduced the success rate (P ≤ 0.001) and vigor (P < 0.001) of secondary peristalsis relative to the effects of the placebo at both distension volumes. Conclusions Secondary peristalsis can be successfully triggered by rapid air injection during HRM. Sildenafil reduces both the success rate and the vigor of secondary peristalsis, similar to that seen with primary peristalsis.

“…Our earlier work has demonstrated that increasing the intensity of stimulation with higher volume promotes a higher success rate but not the vigor of secondary peristalsis in normal subjects. 32 Therefore, the discrepancy can be explained by the fact that the effect of 20 mL injection on the frequency of secondary peristalsis may potentially overcome modulatory impact from codeine, which thus causes no significance in the frequency of 20 mL air injections. This speculation needs to be clarified with different doses of codeine.…”

Section: Discussionmentioning

confidence: 99%

Effects of codeine on esophageal peristalsis in humans using high resolution manometry

Chen

Hung

et al. 2021

Self Cite

Background and Aim: Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their impact on distension-induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults. Methods: Eighteen healthy volunteers (13 men, mean age 27.5 years, aged 20-43 years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid-esophagus. Secondary peristalsis was performed with 10 and 20 mL rapid air injections. Two different sessions including acute administration of codeine (60 mg) or the placebo were randomly performed. Results: Codeine significantly increased 4-s integrated relaxation pressure (IRP-4s) (P = 0.003) and shortened distal latency (DL) (P = 0.003) of primary peristalsis. The IRP-4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10 mL (P = 0.048) and 20 mL (P = 0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10 mL than the placebo (P = 0.007), but not for air injection with 20 mL (P = 0.305). Conclusions: In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.* P-value < 0.05 was considered statistically significant.Data are shown as the mean ± standard errors of the mean. DCI, distal contractile integral; DL, distal latency; IRP-4s, 4-s integrated relaxation pressure; SE, standard error of mean.