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 micrograms/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 to 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.
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D006851:Hydrochloric Acid / Q000009:adverse effects; D011453:Prostaglandins / Q000494:pharmacology* / Q000627:therapeutic use; D013272:Stomach Diseases / Q000188:drug therapy / Q000209:etiology; D013312:Stress, Physiological / Q000150:complications; D013552:Swine
D011453:Prostaglandins; D011464:Epoprostenol; D006851:Hydrochloric Acid