Therapeutical efficacy of a novel chloride transport blocker and an IP3-analogue in vasogenic brain edema.
The efficacy of torasemide, a novel chloride-channel blocker, and of PP56, an IP3 analogue, was currently examined in experimental brain edema. Following trephination in anesthesia rats were subjected to a focal cold injury of the left cerebral hemisphere. Animals of 4 experimental groups receiving either torasemide (i.v. at 30 min before and 6 h after lesion) or PP56 (continuous infusion beginning at 30 min before until 24 h after lesion) at two dose levels were compared with controls administered with i.v. saline. 24 h after trauma the brain was removed from the skull, and the hemispheres were separated in the median plane for gravimetric assessment of hemispheric swelling. Hct, blood gases and body temperature remained constant in all groups. Blood pressure was found to increase in a dose-dependent manner in animals with torasemide. No significant reduction of brain swelling was found in animals with low-dose torasemide (8.51 +/- 0.63%) or low- (7.91 +/- 0.60) and high-dose PP56 (6.85 +/- 1.05%) as compared to the untreated controls. Brain swelling, however, was significantly attenuated by high-dose torasemide to 7.04 +/- 0.36%, as compared to 8.89 +/- 0.29% of the untreated group (p < 0.005). It is currently studied whether torasemide reduces brain swelling when given after the insult.
Berger
S
S
Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University, München, Federal Republic of Germany.
Staub
F
F
Stoffel
M
M
Eriskat
J
J
Schürer
L
L
Baethmann
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005615:Freezing; D007262:Infusions, Intravenous; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D013702:Temporal Lobe / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D000077786:Torsemide
D018118:Chloride Channels; D004232:Diuretics; D007295:Inositol Phosphates; D013449:Sulfonamides; C059368:atrinositol; D000077786:Torsemide