sulprostone and Ischemia

16,16-Dimethyl-PGE2 (PGE2) may interact with one of four prostaglandin type E (EP) receptors, which signal via cAMP (via EP2 or EP4 receptors) or intracellular Ca(2+) (via EP1 receptors). Furthermore, EP3 receptors have several splice variants, which may signal via cAMP or intracellular Ca(2+). We sought to determine the PGE2 receptor interactions that mediate recovery of transmucosal resistance (R) in ischemia-injured porcine ileum. Porcine ileum was subjected to 45 min of ischemia, after which the mucosa was mounted in Ussing chambers. Tissues were pretreated with indomethacin (5 microM). Treatment with the EP1, EP2, EP3, and EP4 agonist PGE2 (1 microM) elevated R twofold and significantly increased tissue cAMP content, whereas the EP2 and EP4 agonist deoxy-PGE1 (1 microM) or the EP1 and EP3 agonist sulprostone (1 microM) had no effect. However, a combination of deoxy-PGE1 and sulprostone stimulated synergistic elevations in R and tissue cAMP content. Furthermore, treatment of tissues with deoxy-PGE1 and the Ca(2+) ionophore A-23187 stimulated synergistic increases in R and cAMP, indicating that PGE2 triggers recovery of R via EP receptor cross talk mechanisms involving cAMP and intracellular Ca(2+).

Topics: Animals; Calcimycin; Calcium Signaling; Culture Techniques; Cyclic AMP; Dinoprostone; Drug Synergism; Electric Impedance; Female; Ileal Diseases; Indomethacin; Intestinal Mucosa; Ionophores; Ischemia; Male; Receptor Cross-Talk; Receptors, Prostaglandin E; Swine

A 34-year-old patient was treated with constant intravenous infusion of sulprostone because of postpartum hemorrhage from a hypotonic uterus. The arm in which sulprostone had been infused was painful 23 h after infusion. A day later, the arm was found to be blueish, edematous and extremely painful as a result of arterial spasm. The vasospasm was probably caused by accidental subcutaneous infusion of sulprostone as a result of a displaced intravenous catheter. A diagnosis of critical limb ischemia was made. Treatment with the prostacyclin-analogue iloprost resulted in full recovery. Critical limb ischemia as a serious complication of sulprostone has not been previously reported.

Topics: Adult; Arm; Diabetes, Gestational; Dinoprostone; Female; Fetal Membranes, Premature Rupture; Humans; Iloprost; Ischemia; Obstetric Labor, Premature; Postpartum Hemorrhage; Pregnancy; Vasodilator Agents