PGF2 alpha mediated cytoprotection: a reassessment.
The demonstration of gastrointestinal ctyoprotection by PGF2 alpha (a supposed vasoconstrictor) has been cited as evidence against alteration of mucosal blood flow as a mechanism for the cytoprotection phenomenon. However, cytoprotection by PGF2 alpha has never been demonstrated in a model having concomitant documentation of gastrointestinal blood flow. This experiment was designed to accomplish two objectives. First, the effect of intravenous PGF2 alpha (0.1, 1.0, 10.0 mcg/kg/minute) on blood flow throughout the gastrointestinal tract was documented in a chloralose anesthetized miniature swine model (n = 7). Second, the effect of intravenous PGF2 alpha (1.0 mcg/kg/minute) on both gastric mucosal blood flow and stress ulceration was assessed during a 3-hour period of hemorrhagic shock in the same model (six controls, six PGF2 alpha). The radiolabeled microsphere technique of blood flow determination was employed.


RESULTS
Intravenous PGF2 alpha significantly decreased myocardial blood flow at all doses employed. Although blood flow in the gastrointestinal tract tended to decrease with the largest dose of PGF2 alpha, this did not reach statistical significance. During shock PGF2 alpha had no effect on gastrointestinal blood flow. Furthermore, there was no evidence of gastric mucosal cytoprotection compared to controls. These results suggest that PGF2 alpha is neither vasoconstrictive nor cytoprotective when sub maximal doses are used. Dismissal of mucosal blood flow as a possible mechanism of prostaglandin-mediated cytoprotection is premature.
D000818:Animals; D015237:Dinoprost; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects; D011460:Prostaglandins F / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000517:prevention & control; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D011460:Prostaglandins F; D015237:Dinoprost