Prostacyclin increases gastric mucosal blood flow via cyclic AMP

Abstract

Although prostacyclin has been shown to inhibit stress-induced gastric mucosal ulceration, the mechanism for this cytoprotection is unknown. This experiment measures the effect of intravenous prostacyclin on gastric mucosal blood flow and any modification of this effect by pretreatment with the phosphodiesterase inhibitor, theophylline. Miniature swine were anesthetized, intubated, and ventilated. Three groups of six animals each were studied: (1) theophylline, (2) prostacyclin, and (3) prostacyclin plus theophylline. After stabilization, baseline gastric mucosal blood flow was measured with radioactive spheres. Theophylline (or vehicle) was then infused at 50 mg/kg/hr × 15 min followed by 2 mg/kg/hr thereafter. After 30 min prostacyclin (or vehicle) was infused at 0.005, 0.05, and 0.5 μg/kg/min for three consecutive 15-min periods, each followed by measurement of gastric mucosal blood flow. Results: At 0.5 μg/kg/min, prostacyclin increased gastric mucosal blood flow despite a drop in mean arterial pressure (50.1 ± 8.4 vs 17.4 ± 4.1 ml/100 g/min). Significant differences in cardiac index were not seen among the three groups. Pretreatment with theophylline potentiated prostacyclin's effect on gastric mucosal blood flow suggesting that prostacyclin increases gastric mucosal blood flow by a mechanism dependent on cyclic AMP (113.2 ± 23.3 vs 50.1 ± 8.4 ml/100 g/min). Since mucosal ischemia is an accepted prerequisite for stress-induced ulceration, prostacyclin's effect on blood flow may contribute to its protective effect on gastric mucosa.