[Relief of experimental cerebral vasospasm by the intrathecal administration of a calcium antagonist (diltiazem)--in comparison with intra-arterial administration].
The effect of an intra-arterial administration of diltiazem on experimental cerebral vasospasm was previously reported by us. In the present study, the effect of diltiazem on cerebral vasospasm, intracranial pressure and systemic blood pressure were investigated using dogs. Cerebral vasospasm was induced by an injection of 5 ml of autologous blood into the cisterna magna. Diltiazem (10(-6) M) was administrated into the cisterna magna and the dilating effect of the drug on the basilar artery was monitored angiographically. The intrathecal administration of diltiazem relieved the vasospasm for more than 30 minutes, same as that of the intra-arterial administration. However, the intracranial and blood pressures remained unchanged. The changes of concentration of the drug in CSF and plasma following the intracisternal administration of 14C-diltiazem were measured using rabbits. The concentration of an administered diltiazem in CSF and plasma was quickly decreased and reduced to 2% of its initial value after one hour (t1/2 = 8 min). Our results show that even the concentration of diltiazem is very low in CSF, the vasodilating effect continues for more than 30 min. This suggests that the intrathecal administration of diltiazem may be useful for the prevention and treatment of the cerebral vasospasm following subarachnoid hemorrhage.
D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004110:Diltiazem / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000494:pharmacology; D004285:Dogs; D007269:Injections, Intra-Arterial; D007278:Injections, Spinal; D007427:Intracranial Pressure / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000503:physiopathology; D011817:Rabbits; D051381:Rats
D001552:Benzazepines; D004110:Diltiazem