Oral Mosapride Attenuates Gastrointestinal Dysmotility During Experimental Endotoxemia in Horses: A Randomized, Blinded Crossover Study.

Overview

• This study examined whether oral mosapride, a medication known to stimulate gut movement, can improve gastrointestinal motility in horses experiencing endotoxemia-induced gut paralysis.
• The research found that mosapride helped restore some gut motility and reduced inflammation effects during experimentally induced endotoxemia in healthy horses.

Introduction to the Study

• Endotoxemia is a condition caused by toxins from bacteria entering the bloodstream, leading to systemic inflammation.
• In horses, endotoxemia often results in gastrointestinal (GI) hypomotility, which means reduced movement of the GI tract, leading to serious complications like postoperative ileus (intestinal paralysis after surgery).
• Mosapride is a prokinetic drug that enhances GI motility by acting on serotonin receptors in the gut.
• The study aimed to determine if oral mosapride remains effective at promoting gut motility during acute endotoxemia caused by lipopolysaccharide (LPS) administration in horses.

Study Design and Methods

• The study was a randomized, blinded, three-period crossover trial involving seven healthy adult horses.
• Each horse experienced three treatments with 14-day washout intervals between:
  • LPS alone (to induce endotoxemia),
  • Mosapride alone, and
  • LPS plus mosapride.
• Mosapride was administered orally at a dose of 2 mg/kg.
• Endotoxemia was induced via intravenous infusion of O55:B5 LPS at 0.03 µg/kg over 30 minutes.
• Researchers measured clinical parameters (heart rate, temperature), hematological variables (white blood cells, inflammatory markers), auscultation of the abdomen, and ultrasonographic evaluation of the stomach and intestines from baseline to 6 hours post-treatment.

Key Findings

• LPS alone caused:
  • Increased heart rate (tachycardia),
  • Elevated body temperature (hyperthermia),
  • Changes in white blood cell counts (leukocyte alterations),
  • Severe gastrointestinal hypomotility (reduced gut movement),
  • Gastric distension (enlarged stomach), and
  • Increased intestinal wall thickness (sign of inflammation).
• Mosapride alone:
  • Increased gastrointestinal motility effectively,
  • Did not cause adverse clinical effects in healthy horses.
• When mosapride was administered with LPS:
  • It partially restored gastrointestinal motility compared to LPS alone, indicating prokinetic effects even during endotoxemia,
  • Reduced gastric distension and thickening of the intestinal wall, suggesting less severe gut inflammation or damage,
  • Was associated with a milder inflammatory response based on hematologic data, compared with LPS treatment alone.

Implications and Conclusions

• Oral mosapride maintains significant prokinetic activity even in the setting of acute endotoxemia, a condition that severely disrupts normal gut motility in horses.
• This suggests that mosapride could be a valuable adjunctive therapy to improve gut motility and reduce inflammation-related gut dysfunction in clinical cases involving endotoxemia or postoperative ileus.
• Further investigations and clinical trials are warranted to evaluate the practical therapeutic benefits and safety of mosapride as a treatment for inflammation-associated gastrointestinal hypomotility in horses.