lacidipine and Ischemic-Attack--Transient

We investigated the effects of lacidipine on focal cerebral ischemia in rats, and these effects were compared with those of nicardipine. Drugs were administered orally 5 min after middle cerebral artery occlusion (MCAO). Neurological scores as described by Bederson et al. (Stroke 17, 472-476, 1986) and cerebral infarct size (CIS) determined by the 2,3,5-triphenyltetrazolium chloride staining method were measured 24 hr after MCAO. Cerebral blood flow (CBF) and energy metabolites were determined by the hydrogen clearance method and an enzymatic method, respectively. In the drug-untreated group, we observed low-CBF of approximate 13 ml/100 g/min during 0.5-6 hr of occlusion and extensive cerebral infarction associated with severe neurologic deficits (ND). Lacidipine at 1 and 3 mg/kg, although it lowered blood pressure, improved low-CBF to approximate 20 ml/100 g/min during 1.5-6 hr of occlusion and increased tissue levels of ATP 6 hr after MCAO in a dose-dependent manner. Nicardipine at 30 mg/kg also improved low-CBF and increased tissue levels of ATP significantly. However, the improvement of low-CBF by nicardipine was transient. Lacidipine at 3 mg/kg reduced CIS and ameliorated ND significantly. In contrast, nicardipine at 30 mg/kg could not ameliorate ND in spite of a significant reduction of CIS similar to that of lacidipine (3 mg/kg). These results suggest that the improvement of focal cerebral ischemia by lacidipine may be partly due to long-lasting improvement of collateral blood supply to the ischemic area.

Topics: Adenosine Triphosphate; Animals; Brain; Calcium Channel Blockers; Cerebral Arterial Diseases; Cerebral Infarction; Cerebrovascular Circulation; Dihydropyridines; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Metabolism; Ischemic Attack, Transient; Male; Neurologic Examination; Nicardipine; Rats; Rats, Sprague-Dawley

We examined the cerebral protective effects of lacidipine (L) using three different types of cerebral ischemia models, and the effects were compared with those of nicardipine (N). (1) In the transient forebrain ischemia model of the rat, oral administration of L (0.3 and 1 mg/kg) before ischemia significantly decreased the number of acidophilic neurons in CA1 regions of the hippocampus 7 days after ischemia. N (3 mg/kg, p.o.) before ischemia also produced a significant reduction in the number of acidophilic neurons, and it's effectiveness was almost the same as that of L (1 mg/kg). (2) In the focal cerebral ischemia model of the rat, oral administration of L (1 and 3 mg/kg) before of after left middle cerebral artery occlusion (MCAO) significantly reduced infarct size at 24 hr after MCAO. Such an ameliorative effect was also observed when N was administered orally. However, the effect of N at 30 mg/kg was less than that of L at 1 mg/kg. (3) In the delayed cerebral vasospasm model of the dog after subarachnoid hemorrhage (SAH), intravertebral artery injection of L (10 micrograms/kg) or N (10 micrograms/kg) dilated the contracted basilar artery 3 days after SAH to the level before SAH. Finally, while both L and N increased cerebral blood flow (CBF) in a dose-dependent manner in conscious normal rat, the increment of CBF induced by L at a given level of reduced-blood pressure was greater than that induced by N. These results indicate that lacidipine may be a potential therapeutic agent that exerts a protective effect against brain damage after cerebral ischemia.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Cerebrovascular Circulation; Dihydropyridines; Disease Models, Animal; Dogs; Ischemic Attack, Transient; Male; Nicardipine; Rats; Rats, Sprague-Dawley