flunarizine and Subarachnoid-Hemorrhage

the aim of this study was to assess and to compare the ability of intrathecal flunarizine and nimodipine to prevent vasospasm in a rabbit model of subarachnoid hemorrhage (SAH).. forty male New Zealand white rabbits were allocated into 5 groups randomly. The treatment groups were as follows: (1) control (no SAH [n = 8]), (2) SAH only (n = 8), (3) SAH plus vehicle (n = 8), (4) SAH plus nimodipine (n = 8), and (5) SAH plus flunarizine (n = 8). Before sacrifice, all animals underwent femoral artery catheterization procedure by open surgery under anesthesia and angiography performed for each animal.. there was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). Basilar artery vessel diameter and luminal section areas in group 4 were significantly higher than in group 2 (p < 0.05). Basilar artery vessel diameter and basilar artery luminal section areas in group 5 were significantly higher than in group 2 (p < 0.05).Basilar artery vessel diameter and basilar artery luminal section areas in group 5 were significantly higher than in group 4 (p < 0.05).. these findings demonstrate that flunarizine has marked vasodilatatory effect in an experimental model of SAH in rabbits.

Topics: Angiography, Digital Subtraction; Animals; Basilar Artery; Calcium Channel Blockers; Disease Models, Animal; Flunarizine; Injections, Spinal; Male; Neurologic Examination; Nimodipine; Rabbits; Subarachnoid Hemorrhage; Time Factors; Vasospasm, Intracranial

Cerebral blood flow and oxygen metabolism were measured and a cerebral angiography was performed in dogs with experimental subarachnoid hemorrhage to assess the relation between arterial narrowing (vasospasm) and the fall of blood flow. Cerebral blood volume and the cerebrovascular CO2 reactivity were also measured to estimate the cerebrovascular reserve. Several groups of dogs were treated with flunarizine in different regimens to assess its possible therapeutic effect.. The experiments were performed in the three-hemorrhage canine model for subarachnoid hemorrhage. Cerebral blood flow and cerebral oxygen metabolism were measured in anesthetized (nitrous oxide) dogs using positron emission tomography in combination with the 15O steady-state method. Basilar artery diameter was evaluated by digital subtraction angiography.. In normal dogs, cerebral blood flow, oxygen consumption, and oxygen extraction ratio were 46.4 +/- 9.0 ml/100 ml per minute, 3.65 +/- 0.76 ml/100 ml per minute, and 39.9 +/- 3.4%, respectively; basilar artery diameter was 1.33 +/- 0.25 mm. Repeated subarachnoid blood injection (3 x 5 ml) reduced basilar artery diameter to < 20% of normal (p < 0.01). Cerebral blood flow was reduced by only 25% (p < 0.001); oxygen consumption was preserved at a low normal level by a 29% compensatory increase of the oxygen extraction (p < 0.001). Cerebral blood volume and cerebrovascular CO2 reactivity remained nearly normal. Early (after the first blood injection) peroral treatment with flunarizine (0.5 mg/kg daily) resulted in less severe basilar artery narrowing (56% of normal; p < 0.05 versus untreated). However, this treatment had no effect on cerebral blood flow, blood volume, oxygen consumption, and extraction.. The observed fall of cerebral blood flow in experimental subarachnoid hemorrhage is not related to arterial narrowing but to an increased cerebrovascular resistance at the level of the small parenchymal vessels, and the latter, in contrast to arterial narrowing, is unaffected by flunarizine.

Topics: Animals; Basilar Artery; Brain; Cerebral Arteries; Constriction, Pathologic; Disease Models, Animal; Dogs; Flunarizine; Oxygen Consumption; Regional Blood Flow; Subarachnoid Hemorrhage; Tomography, X-Ray Computed

A cerebral Ca2+ overload blocker--flunarizine hydrochloride--was used with excellent results for prophylaxis of delayed ischaemic neurological deficit (DIND) in severe subarachnoid haemorrhage. The drug was administered orally at a dose of 10 mg, four times daily for four days, followed by three times daily for three days and twice daily for 14 more days. Of 72 patients treated with flunarizine, only one developed permanent DIND. 37 consecutive patients who were in Fisher's group III and were treated with flunarizine from immediately after early surgery were compared retrospectively with the 37 consecutive Control Group patients, who also belong to Fisher's group III. Among the Control Group patients, eight died from DIND and ten developed infarction from DIND, while flunarizine strongly prevented (p less than 0.001) DIND. Furthermore, the only one DIND was attributable to failure of administration of flunarizine. There were no side-effects from flunarizine. The association of severe angiographic vasospasm was less frequent in the Flunarizine Group (18% vs 57%, p less than 0.02). From this evidence, it might be concluded that flunarizine significantly inhibits the occurrence of severe neurological deficit due to delayed vasospasm. This highly beneficial effect on severe delayed vasospasm might be attributable to its intense inhibitory action on intracellular Ca2+ overloads especially in severe pathological situations.

Topics: Adult; Aged; Aged, 80 and over; Calcium Channel Blockers; Female; Flunarizine; Humans; Ischemic Attack, Transient; Male; Middle Aged; Subarachnoid Hemorrhage

Acute ischemia of the brain induces a cascade of biochemical and physiological events. The final consequences depend on the fact whether ischemia is of transient or permanent, total or partial nature. Alteration of extracellular potassium concentration, intracellular calcium and potassium concentration, development of cytotoxic and vasogenic edema, postischemic hyperfusion and no-reflow phenomenon are important factors which decide about the final fate of functional capacity. CO2 reactivity, autoregulation and hemorheology must be considered when therapeutic approaches are used to influence basic flow during ischemic condition. At present there exists no therapy which has been fully accepted and is able to guarantee benefit to the hypoperfused tissue. Since the calcium metabolism is altered by ischemic processes, substances which act on this metabolism might be of value in the treatment of ischemia and its consequences. However, their beneficial effect on cerebral infarction has not been proven yet. In subarachnoid hemorrhage and migraine calcium antagonists are used to prevent and treat ischemia. In epilepsia calcium overload blockers have been tried by one group with promising results.

Topics: Acute Disease; Brain Edema; Brain Ischemia; Calcium Channel Blockers; Cerebrovascular Disorders; Epilepsy; Flunarizine; Humans; Migraine Disorders; Rheology; Subarachnoid Hemorrhage