Adrenergic agents modify cerebral edema and microvessel ultrastructure in porcine sepsis

To investigate the effects of adrenergic agents on the cerebral response to sepsis.

Prospective, randomized, controlled, experimental animal study.

Medical school research laboratories.

Twenty-eight middle white pigs (25-30 kg).

Pigs were anesthetized, mechanically ventilated, and randomly assigned to one of the following groups: cecal peritonitis (n = 5), cecal peritonitis with dopexamine (n = 5), cecal peritonitis with dopexamine and the beta2-adrenergic receptor antagonist ICI 118,551 (n = 4), cecal peritonitis with methoxamine (n = 5), cecal peritonitis with dopexamine and methoxamine (n = 4), and sham-operated (n = 5). Sham-operated pigs were killed after laparotomy, and pigs with cecal peritonitis were killed 8 hrs after its induction. Samples of frontal cerebral cortex were taken immediately after death, processed for light and electron microscopy, and then subjected to morphometric analysis.

There was significantly more (p <.0005) cerebral perimicrovessel edema in pigs with cecal peritonitis (80.2 microm2 +/- 5.3 sem) than in sham-operated pigs (26.2 microm2 +/- 2.7 sem) and significantly less (p <.0005) perimicrovessel edema in dopexamine-treated pigs with cecal peritonitis (39.8 microm2 +/- 5.5 sem) than in pigs with cecal peritonitis alone (80.2 microm2 +/- 5.3 sem). There was no significant difference between the amount of perimicrovessel edema in pigs with cecal peritonitis treated with dopexamine plus ICI118,551 and pigs with cecal peritonitis alone. The mean cerebral microvessel endothelial cell cross-sectional area in methoxamine-treated pigs with cecal peritonitis (26.3 microm2 +/- 2.6 sem) was significantly greater than that in pigs with cecal peritonitis alone (16.3 microm2 +/- 2.1 sem, p =.008) or in sham-operated pigs (12.3 microm2 +/- 1.3 sem, p =.0005).

Dopexamine protects against cerebral edema formation in sepsis by stimulation of beta2-adrenergic receptors, whereas the alpha1 adrenoceptor agonist methoxamine induces cerebral microvessel endothelial cell swelling.