Protective effect of flunarizine against cerebral hypoxia-anoxia in mice and rats.

Karasawa, Akira; Kumada, Yoko; Yamada, Kôji; Shuto, Katsuichi; Nakamizo, Nobuhiro

doi:10.1248/bpb1978.5.295

Cited by 34 publications

(11 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 Another calcium entry blocker, flunarizine, has been reported to be a potent cerebral vasodilator," to dramatically improve CBF after complete cerebral ischemia in dogs maintained on cardiopulmonary bypass, 12 and to protect the brain of mice and rats against cerebral hypoxia-anoxia. 13 We therefore studied the effects of flunarizine on CBF, cerebral metabolism of oxygen (CMRO 2 ), and neurologic recovery in an established intact canine model of complete cerebral ischemia and compared the results to those obtained from untreated groups 4 -14 and from pre-treated…”

mentioning

confidence: 99%

Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia.

Newberg¹,

Steen²,

Milde³

et al. 1984

Stroke

View full text Add to dashboard Cite

Ten minutes of cerebral ischemia was produced in 12 dogs by temporary ligation of the venae cavae and aorta. After reperfusion the dogs received the calcium entry blocker, flunarizine, 6 micrograms/kg infused over a ten minute period. Cerebral blood flow (CBF) and metabolism (CMRO2) were measured pre-ischemia and for 2 h post-ischemia in 6 dogs. At the end of the study brain biopsies were analyzed for cerebral metabolites. Neurologic recovery was evaluated for up to 48 h post-ischemia in an additional 6 dogs. The results of each study were compared to those previously obtained in untreated animals. The cerebral blood flows (when expressed as a percent of the pre-ischemic control value) of the flunarizine-treated and untreated groups were similar throughout the post-ischemic period. Following an initial hyperemia, the CBF fell to significantly less than the pre-ischemic control values, and remained approximately 26% of control during the final 90 min in both groups. The CMRO2 was also the same for both groups. Cerebral metabolites were similar although abnormal in both groups. Flunarizine produced pulmonary edema in 5 of 6 dogs studied for neurologic recovery. Four of these dogs died within 12 h and another dog demonstrated severe neurologic damage. None of the untreated dogs developed pulmonary edema, but 6 of 7 dogs evidenced severe neurologic damage or were dead at 48 h. Thus, flunarizine failed to improve either cerebral blood flow or neurologic outcome when given after complete cerebral ischemia in the dog. A cardiodepressive effect of flunarizine might have contributed to the poor neurologic outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

mentioning

confidence: 99%

Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia.

Newberg¹,

Steen²,

Milde³

et al. 1984

Stroke

View full text Add to dashboard Cite

show abstract

“…These effective doses of KMK are not consi dered unusual because other drugs with a protective ac tion against ischemic disorders also need to be given in high doses (e.g., the effective dose of flunarizine for KCN induced death is 120 times higher than the normal clinical dose (16), and the dose of vinpocetine for ischemia is 80 times higher (13)). The protective effects of flunarizine, a Ca" antagonist, against cerebral hypoxia-anoxia in mice and rats (16) and against ischemic injury in gerbils (20) have been reported previously. In the present experiments, flunarizine also showed protective effects against cerebral ischemia, hypoxia and anoxia.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Kamikihi-To, a Traditional Chinese Medicine, against Cerebral Ischemia, Hypoxia and Anoxia in Mice and Gerbils

Nishizawa¹,

Ito²,

Saito³

et al. 1994

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-The protective effects of Kamikihi-To (KMK), a traditional Chinese medicine, against cerebral ischemia, hypoxia and anoxia were investigated with various experimental models in mice and ger bils. KMK (2.0 g/kg/day, p.o. for 5 days) significantly prolonged the survival time of mice subjected to bilateral common carotid artery occlusion. KMK (0.5 and 2.0 g/kg/day, p.o. for 5 days) also prolonged the survival time of mice injected with N-methyl-D-aspartic acid (NMDA: 80 mg/kg, i.v.). Furthermore, KMK (in a diet containing 8% KMK given orally for 34 days) showed protective effects against delayed neuronal death in CAI pyramidal cells in the gerbil hippocampus after transient forebrain ischemia. On the other hand, we failed to show any protective effects of KMK (0.5-2.0 g/kg/day, p.o. for 5 days) against nor mobaric hypoxia and KCN-induced cytotoxic anoxia in mice. These results suggest that KMK may have pro tective effects against cerebral ischemic disorders, but not against severe hypoxic and anoxic disorders.

show abstract

“…0 1 hypoxia-anoxia 22 and improve postischemic hypoperfusion. 23 Nimodipine prevented postischemic impaired cerebral reperfusion, and promoted functional recovery after cerebral ischemia.…”

Section: Controlmentioning

confidence: 99%

“…23 Nimodipine prevented postischemic impaired cerebral reperfusion, and promoted functional recovery after cerebral ischemia. 24 -M While the mechanism of the protective effect of calcium entry blocker against cerebral ischemia is attributed to a cerebral vasodilat-^ ^| ing action, 22 " 25 some authors suggest the involvement of some other unknown mechanism 22 or protection from mitochondrial calcium accumulation. 23 Hossmann et al M observed that postischemic accumulation of calcium in the brain tissue could not be prevented by the calcium antagonist flunarizine.…”

Section: Controlmentioning

confidence: 99%

Effect of nimodipine on cerebral functional and metabolic recovery following ischemia in the rat brain.

Mabe¹,

Nagai²,

Takagi³

et al. 1986

Stroke

View full text Add to dashboard Cite

SUMMARY Whether the calcium entry blocker, nimodipine, prevents the increase in the concentration of free fatty adds and metabolic disturbances during ischemia and promotes functional and metabolic recovery after reclrculation were examined.Severe forebrain ischemia in rats was induced by four-vessel occlusion with mild hypotension. After 30 minutes of ischemia, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemk level.Recovery of EEG activity following recirculation was better in the nimodipine-treated group than in the control group. During the ischemic period, there were no significant differences in accumulation of free fatty acids or in depletion of ATP between treated and control groups. At 120 minutes following recirculation, recovery of the ATP level was significantly better in the treated group than in the control group. Therefore, the promotion of functional and metabolic recovery by nimodipine-treatment is suggested to be not due to the prevention of an accumulation of free fatty acids nor to the depletion of ATP during the ischemic period, but to either Improvement of postischemic hypoperfusion or a direct action on metabolic processes during reperfusion period. Stroke Vol 17, No 3, 1986RECENTLY, considerable interest has been centered on the role of calcium in irreversible ischemic brain damage. 1 2 Ischemic depolarization of cell membrane is associated with a precipitous influx of calcium from the extracellular to the intracellular compartment, and, as a consequence, intracellular calcium increase. 3 The elevated cytosolic calcium induces impairment of the mitochondrial function that leads to failure of ATP production and induces activation of Ca 2+ -ATPase resulting in a further reduction of ATP.

show abstract

Protective effect of flunarizine against cerebral hypoxia-anoxia in mice and rats.

Cited by 34 publications

References 9 publications

Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia.

Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia.

Protective Effects of Kamikihi-To, a Traditional Chinese Medicine, against Cerebral Ischemia, Hypoxia and Anoxia in Mice and Gerbils

Effect of nimodipine on cerebral functional and metabolic recovery following ischemia in the rat brain.

Contact Info

Product

Resources

About