16-16-dimethylprostaglandin-e2 and Hemorrhage

We used in vivo microscopy and laser-Doppler velocimetry to examine the effects on the gastric mucosal microcirculation and in gastric mucosal blood flow of agents that induce acute gastric mucosal damage. In vivo microscopic observation of superficial mucosal capillaries revealed vascular stasis within a mean of 54, 81, or 61 s after 100% ethanol, 0.6 N HCl, or 0.2 N NaOH, with the subsequent development of hemorrhagic mucosal lesions. Mucosal blood flow estimated by laser-Doppler velocimetry decreased by 30% at 5 min after luminal application of 100% ethanol, and decreased further to about 40% of basal levels by 15 min. The decreased mucosal blood flow 15 min after application of 50% ethanol correlated with the extent of hemorrhagic mucosal lesions. Examination of the submucosal vessels that supply and drain the mucosa showed moderate dilation of small arterioles 1, 3, and 6 min after exposure to 100% ethanol but there were no consistent changes in venules. Mild vasoconstriction of small- and medium-sized venules could be detected 6, 10, and 15 min after NaOH but not after exposure to HCl. Pretreatment with 16,16-dimethyl prostaglandin E2 or sodium thiosulfate before exposure of the mucosa to ethanol prevented capillary stasis, maintained mucosal blood flow, and prevented the development of hemorrhagic gastric mucosal lesions. Topical mucosal application of 16,16-dimethyl prostaglandin E2 decreased, whereas topical exposure to sodium thiosulfate increased gastric mucosal blood flow, indicating that change in blood flow per se is an unlikely mediator of protection.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Capillaries; Ethanol; Female; Gastric Mucosa; Hemorrhage; Hydrochloric Acid; Microcirculation; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Regional Blood Flow; Rheology; Sodium Hydroxide; Stomach Diseases; Thiosulfates

Acute edematous pancreatitis was induced in cats by perfusing activated pancreatic enzymes through their pancreatic ducts. The ducts had been made permeable to large molecules by one of two techniques. The cats either received ethanol (2 ml/kg every 8 h) and aspirin (25 mg/kg every 8 h) orally for 48 h or had their pancreatic ducts perfused for 1 h with 7.5 mM glycodeoxycholate. When the same procedure was followed, but using 16,16-dimethyl prostaglandin E2 (dmPGE2) (2 micrograms/kg X h infused intravenously for 1 h before and during ductal perfusion with activated enzymes), hemorrhagic pancreatitis developed instead. To investigate whether an increase in pancreatic blood flow or microvascular permeability (both caused by dmPGE2) was important in this phenomenon, we tested the effects of isoproterenol (which increased blood flow) and histamine (which increased microvascular permeability) in the model. Thus in similar experiments, either isoproterenol (0.3 micrograms/kg . min) or histamine phosphate (2 micrograms/kg . min) was infused instead of dmPGE2. The animals that received histamine also developed hemorrhagic pancreatitis. Those that received isoproterenol did not. These observations suggested that an increase in microvascular permeability in the pancreas converted edematous pancreatitis to hemorrhagic pancreatitis. These findings suggest also that clinical studies using prostaglandins to treat patients with pancreatitis should be approached with caution.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Aspirin; Capillary Permeability; Cats; Ethanol; Glycodeoxycholic Acid; Hemorrhage; Histamine; Isoproterenol; Pancreas; Pancreatic Juice; Pancreatitis; Prostaglandins E, Synthetic; Regional Blood Flow

The effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) on histologic and microcirculatory changes in alcohol-induced gastric mucosal injury was studied. A histologic study confirmed that dmPGE2 does not protect the surface mucous cells against ethanol injury but does protect against the deeper necrotic lesion. Both the gross injury and the necrotic lesion were as severe after 1 min of ethanol exposure as after 60 min. A study of benzidine-stained sections and hematoxylin and eosin-stained sections revealed marked engorgement of microvessels and hemorrhage in the superficial mucosa after ethanol injury. Pretreatment with dmPGE2 prevented these. An in vivo fluorescent microscopy study revealed that there was total stasis of blood flow in the injured area. After the intravascular injection of a fluorescein-albumin conjugate, the conjugate filled microvessels in grossly normal areas of mucosa but not in grossly injured areas. Pretreatment with dmPGE2 prevented this microcirculatory change. This alcohol-induced stasis of flow in injured areas may be of pathogenetic significance and prostaglandin protection might involve prevention of this microcirculatory change.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Eosine Yellowish-(YS); Ethanol; Gastric Mucosa; Hematoxylin; Hemoglobins; Hemorrhage; Male; Microcirculation; Microscopy, Fluorescence; Necrosis; Prostaglandins; Rats; Rats, Inbred Strains; Staining and Labeling