Prostacyclin-mediated gastric cytoprotection is dependent on mucosal blood flow

Although prostacyclin (PGI₂) causes an increase in resting gastric mucosal blood flow, this effect is not thought to be correlated with its cytoprotective action. This study questions that hypothesis by assessing whether PGI₂ cytoprotection occurs in the presence of decreased gastric mucosal blood flow. Twenty-four miniature swine were anesthetized with chloralose, ventilated, and catheterized to measure cardiac output and arterial pressure and to inject microspheres. An orogastric tube was placed for infusion of 2.5% autogenous bile in isotonic HCl (2 ml/kg/hr). Four experimental groups were used: I, control (no drugs); II, vasopressin (0.25 U/min intravenously); III, PGI₂ (0.1 μg/kg/min intravenously); and IV, vasopressin and PGI₂ combined. Gastric mucosal blood flow was documented at baseline and at 1, 2, and 3 hours of drug infusion by radiolabeled-microsphere technique. Stomachs were harvested and photographed, and lesions were scored (0 to 3) by blinded observers. Gastric mucosal blood flow was decreased (50%) in both groups that received vasopressin, increased (300%) in animals that received PGI₂ alone, and unchanged in controls. All animals that received vasopressin, whether alone or with PGI₂, developed mucosal injury (mean score 2.5 versus 2.2). Group I and group III animals did not develop lesions. The results of this study demonstrate that PGI₂ failed to elevate gastric mucosal blood flow, which was already depressed by vasopressin, and that PGI₂ failed to protect the gastric mucosa from injury in the presence of reduced blood flow. This suggests that PGI₂ cytoprotection is linked to its effect on gastric mucosal blood flow.