Indomethacin-induced changes in canine gastric mucosal haemodynamics and haemoglobin oxygenation, and the effects of topical anti-ulcer agents

Abstract Changes in gastric mucosal haemoglobin concentration (mucosal blood volume), mucosal haemoglobin oxygenation, mucosal blood flow and gastric arterial blood flow caused by indomethacin, an ulcerogenic agent, and anti-ulcer agents were investigated in the stomach flap of anesthetized dogs. Indices of mucosal haemoglobin concentration and haemoglobin oxygenation, mucosal blood flow and arterial blood flow to the stomach flap were measured simultaneously. The intravenous injection of indomethacin (10 mg/kg) caused an immediate decrease in mucosal haemoglobin concentration with a gradual decrease in mucosal and arterial blood flow, and a slight decrease in mucosal haemoglobin oxygenation. The topical application of prostaglandin E₂ (10 μg/ml) and spizofurone (a new anti-ulcer agent, 1 mg/ml) to the mucosa significantly increased these parameters, and remedied the decreases of these parameters caused by indomethacin. Cimetidine (20 mg/ml), pirenzepine (10 mg/ml) and proglumide (40 mg/ml) given topically did not significantly increase these parameters in the resting state or the indomethacin-induced ischaemic state. This study indicates that: indomethacin decreases gastric haemodynamics, and that improvement occurred with application of mucosal protective agents (i.e. prostaglandin E₂ and spizofurone) and changes in mucosal blood concentration were closely correlated with those in mucosal blood flow and arterial blood flow, but correlated less well with those in the case of haemoglobin oxygenation.