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Metoclopramide inhibits development of esophageal varices in rat model
M Ohta1, M Hashizume, K Tanoue
1Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
We examined the preventive effect of metoclopramide on the development of esophageal varices in a rat model. Thirty rats were divided into three groups: metoclopramide (7.5 mg/kg twice a day, intraperitoneally), control group I (saline 2 ml/kg twice a day, intraperitoneally), and control group II (incised lower esophageal sphincter and metoclopramide 7.5 mg/kg twice a day, intraperitoneally). On the 14th postoperative day, lower esophageal sphincter pressure in the metoclopramide group (8.6 +/- 1.4 cm H2O) increased more than in the control groups (5.4 +/- 0.5, 5.0 +/- 0.5 cm H2O, P < 0.01). Development of small collateral vessels from the spleen to the retroperitoneum was evident only in the metoclopramide group, as seen on the portography (P < 0.01). Histologically, the variceal area of the horizontal cross section of the esophagus in the metoclopramide group (0.62 +/- 0.26 mm2) was significantly smaller than in the controls (2.67 +/- 0.95, 2.78 +/- 0.82 mm2), determined using an image processor-analyzer for photographing histological specimens (P < 0.01). We also investigated the effect of metoclopramide on smooth muscle cells in the rat portal vein, using isometric-tension recording. Metoclopramide relaxed the smooth muscle precontracted with norepinephrine, in a concentration-dependent manner. Thus, metoclopramide inhibits the development of esophageal varices in this rat model due to both an increase in resistance of the lower esophagus and to development of small collaterals.
Insights
Metoclopramide effectively prevented esophageal varices in a rat model by increasing lower esophageal sphincter pressure and promoting collateral vessel development. This drug demonstrated a significant reduction in variceal area, suggesting a novel therapeutic potential.
Area of Science:
- Gastroenterology
- Pharmacology
- Surgical Research
Background:
- Esophageal varices are a serious complication of portal hypertension.
- Preventive strategies for esophageal varices are crucial for patient management.
- Metoclopramide's effects on esophageal pressure and vascularity warrant investigation.
Purpose of the Study:
- To evaluate the preventive efficacy of metoclopramide against esophageal variceal development in a rat model.
- To elucidate the mechanisms underlying metoclopramide's potential protective effects.
Main Methods:
- A rat model was used, with groups receiving metoclopramide, saline control, or saline with a lower esophageal sphincter incision.
- Lower esophageal sphincter pressure was measured, and portography was performed to assess collateral vessel formation.
- Histological analysis quantified the variceal area, and isometric-tension recordings assessed metoclopramide's effect on portal vein smooth muscle.
Main Results:
- Metoclopramide significantly increased lower esophageal sphincter pressure compared to controls (P < 0.01).
- Development of small collateral vessels was observed exclusively in the metoclopramide group (P < 0.01).
- Histological analysis revealed a significantly smaller variceal area in the metoclopramide group (P < 0.01), and metoclopramide demonstrated a concentration-dependent relaxation of portal vein smooth muscle.
Conclusions:
- Metoclopramide inhibits the development of esophageal varices in this rat model.
- The preventive effect is attributed to increased lower esophageal resistance and the promotion of small collateral circulations.
- Metoclopramide's direct effect on vascular smooth muscle may also contribute to its therapeutic potential.