geranylgeranylacetone and Gastrointestinal-Hemorrhage

Upper gastrointestinal bleeding is a lethal complication after open heart surgery. We designed a prospective randomized trial to test the efficacy of different antisecretory agents to prevent upper gastrointestinal disease after operation.. A total of 210 patients were divided into 3 groups: group I had 70 patients who had mucosal protection (teprenone 150 mg/day), group II had 70 patients who had histamine2-receptor antagonist (ranitidine 300 mg/day), and group III included 70 patients who had a proton pump inhibitor (rabeprazole 10 mg/day). Gastric fiberscopy was used in all patients postoperatively during days 5 to 7. We compared the 3 groups in terms of endoscopic findings. Four patients (5.7%) had gastric bleeding complications in each of groups I and II; 2 died of coagulopathy. In group III no patients had gastric bleeding. The incidence of hemorrhagic gastritis was significantly higher in groups I (22.9%) and II (15.7%) than in III (2.9%) (p=0.0003). The incidence of active ulcers was also significantly higher in groups I (28.6%) and II (21.4%) than in III (4.3%) (p=0.0001).. Early medication postoperative by a proton pump inhibitor was shown to be the most effective treatment and indeed might be described as mandatory to prevent upper gastrointestinal diseases after open heart surgery.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Cardiac Surgical Procedures; Diterpenes; Endoscopy, Gastrointestinal; Gastritis; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Incidence; Omeprazole; Postoperative Complications; Premedication; Proton-Translocating ATPases; Rabeprazole; Ranitidine; Ulcer; Upper Gastrointestinal Tract

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, CAS 11911-87-6) in preventing acute gastritis was examined in rats by stomach perfusion. Teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and omeprazole (CAS 73590-58-6) were used as control drugs. Severe gastric hemorrhage was observed in conscious restrained rats, 1 h after treatment with indometacin (20 mg/kg i.p.). Pretreatment with rebamipide (3, 10 or 30 mg/kg s.c.) suppressed the hemorrhage induced by indometacin plus restraint stress, being more effective than teprenone or cimetidine. Pretreatment with omeprazole (30 mg/kg s.c.) did not suppress the gastric hemorrhage. Superoxide dismutase (30,000 U/kg s.c.) significantly decreased the hemorrhage. Anti-rat PMN (polymorphonuclear leukocytes), 1 ml/kg i.v., which caused depletion of circulating neutrophils, also suppressed the hemorrhage induced by indometacin plus restraint stress. Thus reactive oxygen species derived from neutrophils may play a role in the occurrence of the hemorrhage during acute gastritis induced by indometacin with restraint stress.

Topics: Acute Disease; Alanine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Catalase; Cimetidine; Diterpenes; Gastritis; Gastrointestinal Hemorrhage; Indomethacin; Leukocyte Count; Male; Neutrophils; Omeprazole; Perfusion; Quinolones; Rats; Rats, Wistar; Restraint, Physical; Stress, Psychological; Superoxide Dismutase

The effects of teprenone (6,10,14,18-tetramethyl-5,9,13, 17-nonadecatetraen-2-one) on changes in gastric mucosal blood flow, adenosine triphosphate (ATP) content, and incidence of histologic lesions were evaluated in rat gastric mucosa after hemorrhage and retransfusion.. Teprenone (100 mg/kg) was administered orally once a day for 3 consecutive days. On the 3rd day hemorrhage was induced, withdrawn blood (retransfusion) was returned, and the above variables were determined.. Teprenone significantly inhibited the decreases in blood flow and index of mucosal oxygen saturation (ISO2) during hemorrhage in the corpus and antral mucosa. However, no effect of teprenone was observed on systemic blood pressure and ATP levels after hemorrhage and retransfusion. Teprenone significantly (p < 0.05) decreased both the incidence of ischemic lesions and the increase in the severity of lesions after retransfusion in both mucosal regions.. From these results, it is concluded that the protective effect of teprenone on blood flow was partly responsible for its inhibitory effect on the incidence of lesions in the rat stomach in this hypovolemic shock model, although the former effect might be not a direct effect on systemic vascular tone.

Topics: Adenosine Triphosphate; Animals; Anti-Ulcer Agents; Blood Transfusion, Autologous; Disease Models, Animal; Diterpenes; Energy Metabolism; Gastric Mucosa; Gastrointestinal Hemorrhage; Hemodynamics; Male; Rats; Rats, Wistar; Shock