title: Hyponatremia-induced brain edema in guinea pigs is reduced by treatment with the novel anion transport inhibitor L-644,711.
abstract: Cerebral edema in various disease states may result from astroglial swelling due to increased NaCl uptake mediated by enhanced Cl-HC03 exchange. We evaluated this mechanism in the pathogenesis of cerebral edema in acute hyponatremia by administering L-644,711, a fluorenyloxyacetate derivative that functions as an anion exchange inhibitor, to guinea pigs with severe reductions in serum Na+ concentration. Acute hyponatremia was induced for 54 hr by daily injections of arginine vasopressin (10 U/day) and 5% dextrose in water (7.5% body wt/day). Experimental animals received L-644,711, 20 mg/kg/day, while controls were given an equal volume of the diluent. This regimen lowered the serum Na from normal levels to 108 +/- 3 and 109 +/- 4 mM in experimental and control animals, respectively. Drug treatment resulted in less cerebral edema characterized by a reduction in brain total tissue water 432 +/- 4 vs 466 +/- 8 ml/100 g dry wt experimental vs control, P less than 0.005. This difference was composed mainly of less expansion of the intracellular water space, 287 +/- 11 vs 323 +/- 9 ml/100 g dry wt experimental vs control, p less than 0.005. The cerebral cortical Na+ +Cl content was reduced from 55.5 +/- 1.3 (control) to 39.5 +/- 1.1 mEq/100 g dry wt (experimental), p less than 0.01. These results indicate that treatment of guinea pigs with L-644,711 decreases brain NaCl content and attenuates cerebral edema during severe acute hyponatremia without normalizing the serum Na+ concentration.
authors.affiliation: Department of Pediatrics, Schneider Children's Hospital of Long Island Jewish Medical Center, New Hyde Park, NY.
authors.forename: H
authors.initials: H
authors.lastname: Trachtman
authors.forename: E J
authors.initials: EJ
authors.lastname: Cragoe
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use*; D005449:Fluorenes / Q000494:pharmacology / Q000627:therapeutic use*; D006168:Guinea Pigs; D007010:Hyponatremia / Q000150:complications*; D008297:Male
chemical_list: D004232:Diuretics; D005449:Fluorenes; C053396:L 644711