Treatment of tyramine-induced brain edema with anion transport inhibitor L-644, 711

Ba, Faraj; Ej, Cragoe; Sarper, R.; Camp, Mel; Malveaux, Eugene

doi:10.1016/0024-3205(88)90341-4

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…This assumption is supported by findings on blocking of anion carriers in red blood cells by such diuretics as furosemide, a structural analog of torasemide (see earlier) (Brazy and Gunn, 1976). Other inhibitors of anion carriers, for example alcanoic acids and their analogs, with limited saluretic properties, were also effective in attenuating brain edema (Cragoe et al, 1986;Kimelberg et al, 1988;Faraj et al, 1988;Staub et al, 1993).…”

Section: Discussionmentioning

confidence: 79%

Treatment of Vasogenic Brain Edema with the Novel Cl⁻ Transport Inhibitor Torasemide

Staub

Stoffel²,

Berger³

et al. 1994

Journal of Neurotrauma

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The efficacy of the diuretic agent torasemide, which antagonizes the Na+/K+/Cl- cotransport and Cl- channels, was investigated to determine its inhibition of brain edema from a focal cerebral lesion. For this purpose, cold injury of the brain was induced in 50 Sprague-Dawley rats while monitoring arterial blood pressure. The brain was removed for gravimetric assessment of swelling of the traumatized hemisphere 24 h after trauma. The water content was also determined after drying the cerebral hemispheres for 24 h. Animals were divided into five groups. A control group with trauma received vehicle only; two other groups received 1.0 or 10.0 mg torasemide/kg body weight 30 minutes before and 6 h after trauma (n = 10-12). Administration of the drug after the insult was also investigated in animals with application of vehicle or 10.0 mg/kg of torasemide at 30 minutes and 6 h following the brain lesion (n = 8). Torasemide did not affect important physiologic variables, such as the arterial pO2, pCO2, pH, hemoglobin, hematocrit, or plasma osmolality, while increasing blood pressure (p < 0.01). The blood pressure response notwithstanding, treatment significantly attenuated hemispheric brain swelling from trauma. In control animals without treatment, cold injury led to hemispheric swelling of 8.89%. In animals with 1 mg torasemide/kg BW, brain swelling amounted to 8.51% and to 7.04% in animals receiving 10 mg/kg before and after the insult (p < 0.005). Treatment was also found to attenuate the increase in tissue water content from trauma, but without reaching statistical significance. Postinsult treatment with torasemide (10 mg/kg BW) at 30 minutes and 6 h after trauma was again associated with a significant reduction in hemispheric brain swelling, which in this group amounted to 7.46% compared with 9.76% in the untreated controls (p < 0.005). The increase in the cerebral water content from trauma was also significantly blunted in the latter experiments (p < 0.01). The present data indicate a remarkable therapeutic potential of the novel diuretic agent torasemide to reduce vasogenic brain edema from an acute cerebral lesion. It is surmised that the compound specifically interferes with Cl- transport mechanisms, which apparently are activated in edematous brain involving neuronal and glial cells, for example. This conclusion is supported by in vitro observations that torasemide inhibits the swelling of glial cells from acidosis. On the other hand, it is unlikely that gross dehydration of the brain secondary to the induction of diuresis by the agent played a role, because hematocrit and plasma osmolality were not found to be affected.

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Section: Discussionmentioning

confidence: 79%

Treatment of Vasogenic Brain Edema with the Novel Cl⁻ Transport Inhibitor Torasemide

Staub

Stoffel²,

Berger³

et al. 1994

Journal of Neurotrauma

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“…In spite of such uncertainties, treatment of excitotoxin-mediated CNS injury with agents such as L644,7 11 might provide a potentially useful additional or alternative therapy to the proposed use of NMDA receptor blockers (Simon et al, 1984;Wieloch, 1985;Choi, 1988). Indeed, we have shown that L644,7 11 and related compounds lead to improved mortality and morbidity in an experimental closed head injury model (Nelson et al, 1982;Cragoe et al, 1986;Kimelberg et al, 1987) and in a tyramine-induced brain edema model in dogs (Faraj et al, 1988). The parent compound ethacrynic acid was also found to be effective in a preliminary clinical trial (Yen et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures

et al. 1990

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“…Evidence indicates that prevention of astrocytic injury is a function of the effectiveness of these compounds as specific Cl -/HCO3 exchange inhibitors (Cragoe et al, 1982(Cragoe et al, , 1986. One anion transport inhibitor, L-644,711, looks particularly promising in the prevention of brain edema and hypoxic-ischemic damage to astrocytes (Kimelberg et al, 1987;Barron et al, 1988;Faraj et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Loop diuretic derivative L-644, 711 inhibits K+-stimulated cellular injury in neonatal guinea pig cortical astrocytes

Thakran

Nelson

Leuschen

1994

Molecular and Chemical Neuropathology

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An early pathological rise in extracellular K+ following acute hypoxia results in Cl- uptake into astrocytes through the Cl/HCO3- exchanger with an osmotic equivalent of water. This study addressed effects of the anion transport inhibitor, L-644,711, (5,6,-dichloro-2,3, 9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluroen-7-yl)oxyacetic acid. Confluent primary cultures from neonatal guinea pigs, characterized as > 95% astrocytes with antiserum to glial fibrillary acidic protein, were manipulated by incubation in either basal buffer (BB) with the ionic composition of Dulbecco's minimum essential media (DMEM) or one with high extracellular K+ (HiK). Incubation in 27 or 60 mM Hik significantly reduced cell viability and precipitated a time-dose dependent increase in lactate dehydrogenase (LDH) efflux (30 min to 4 h). L-644,711 was not cytotoxic, and significantly inhibited HiK-stimulated LDH efflux. The optimal effective dose of L-644,711 for preventing injury in guinea pig astrocytes was 10(-11)M when administered simultaneously with the HiK paradigm or in reversing injury when administered 30 min after exposing cells to HiK. These findings indicate the potential usefulness of agents which modify ion transport processes in hypoxic-ischemic cerebral injury.

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Treatment of tyramine-induced brain edema with anion transport inhibitor L-644, 711

Cited by 5 publications

References 16 publications

Treatment of Vasogenic Brain Edema with the Novel Cl⁻ Transport Inhibitor Torasemide

Treatment of Vasogenic Brain Edema with the Novel Cl⁻ Transport Inhibitor Torasemide

Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures

Loop diuretic derivative L-644, 711 inhibits K+-stimulated cellular injury in neonatal guinea pig cortical astrocytes

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Treatment of tyramine-induced brain edema with anion transport inhibitor L-644, 711

Cited by 5 publications

References 16 publications

Treatment of Vasogenic Brain Edema with the Novel Cl− Transport Inhibitor Torasemide

Treatment of Vasogenic Brain Edema with the Novel Cl− Transport Inhibitor Torasemide

Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures

Loop diuretic derivative L-644, 711 inhibits K+-stimulated cellular injury in neonatal guinea pig cortical astrocytes

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Treatment of Vasogenic Brain Edema with the Novel Cl⁻ Transport Inhibitor Torasemide

Treatment of Vasogenic Brain Edema with the Novel Cl⁻ Transport Inhibitor Torasemide