Role of calcium antagonists in cerebral arterial spasm.
Spasm of the large cerebral arteries at the base of the brain causes delayed ischemic neurologic deficits in approximately 30% of patients after a subarachnoid hemorrhage from an intracranial aneurysm. In vitro chamber studies have shown that both dog and human large cerebral artery segments contract to a variety of vasoactive agents, and the dog and human segments are remarkedly similar in their responses. The source of calcium necessary to initiate contraction was found to be extracellular for large cerebral arteries. In contrast, systemic arteries such as the femoral artery use a bound intracellular pool of calcium for contraction. The calcium antagonists nifedipine and nimodipine were found to selectively inhibit the contractions of large cerebral arteries but not the femoral artery. In vivo experiments demonstrated that both nifedipine and nimodipine, given sublingually, would prevent and reverse cerebral arterial spasm in the dog after a subarachnoid hemorrhage. Nimodipine was found to be more potent, both in the chamber and in the live dog experiments. Nimodipine significantly decreased the occurrence of severe neurologic deficits from spasm alone in a multi-institutional, prospective, double-blind, randomized, placebo-controlled trial.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004285:Dogs; D004311:Double-Blind Method; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects; D009539:Nicotinic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D009553:Nimodipine; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D009553:Nimodipine; D009543:Nifedipine