Yasunobu Goto

Milrinone for the treatment of cerebral vasospasm after subarachnoid hemorrhage: report of seven cases.

OBJECTIVEThe intra-arterial infusion of papaverine has been used for dilation of spastic cerebral vessels after aneurysmal subarachnoid hemorrhage, although its efficacy is controversial. Milrinone is an inotropic drug that dilates vessels by phosphodiesterase inhibition in a mechanism similar to that of papaverine. We examined the effects of intra-arterial and subsequent intravenous administration of milrinone on patients with symptomatic cerebral vasospasm. METHODSSeven patients with cerebral vasospasm were enrolled in this study. Milrinone was delivered intra-arterially via catheter at a rate of 0.25 mg/min. The total delivered dose was between 2.5 and 15 mg. Radiological measurement of the middle cerebral artery diameter and cerebral blood flow was carried out before and after arterial infusion. Intravenous treatment followed at 0.50 or 0.75 &mgr;g/kg/min for up to 2 weeks from the onset of subarachnoid hemorrhage. RESULTSDilation of the vasospastic vessels occurred in all patients. The rate of cerebral blood flow was calculated in six patients and was increased in all. Subsequent intravenous infusion was effective in preventing a recurrence of symptomatic vasospasm in four of the seven patients. CONCLUSIONIt is suggested that milrinone was effective and safe for the treatment of cerebral vasospasm after subarachnoid hemorrhage in the patients in this series. Intra-arterial infusion with adjunctive intravenous infusion holds promise as a clinically advantageous treatment regimen.

Degradation of phospholipid molecular species during experimental cerebral ischemia in rats.

Previous investigators have shown that free fatty acids that accumulate during ischemia are an indicator of evolution in ischemic brain damage. Our study describes the temporal relations between free fatty acid accumulation and degradation of phospholipid molecular species after cerebral ischemia. Using the four-vessel occlusion model of adult Wistar rats, we analyzed quantitatively the cerebral phospholipid molecular species of diacyl phosphatidylcholine and diacyl phosphatidylethanolamine and released free fatty acids during ischemia. Total diacyl phosphatidylcholine molecular species decreased gradually but did not show any significant difference even at 60 minutes. By contrast, total diacyl phosphatidylethanolamine abruptly decreased after 5 minutes and continued to decrease significantly thereafter. Polyunsaturated molecular species showed a higher ratio of degradation than saturated and monounsaturated molecular species of either phosphatidylcholine or phosphatidylethanolamine. Total free fatty acid accumulated according to the time elapsed, and statistical significance was obtained after 10 minutes. Free arachidonic and docosahexaenoic acids were attributed to these significant accumulations at 10, 15, and 30 minutes. At 60 minutes, individual free fatty acids increased nonspecifically. Free fatty acids, which are hydrolyzed from phospholipid classes, are known to be further metabolized to bioactive substances such as prostaglandins and leukotrienes. Rapid degradation of phospholipid molecular species, especially of diacyl polyunsaturated molecular species, could be an important finding to membrane perturbation. Effective prevention of these changes might enhance tolerance to ischemic brain damage.

Degradation of Mitochondrial Phospholipids During Experimental Cerebral Ischemia in Rats

Changes in content of brain mitochondrial phospholipids were examined in rats after 30 and 60 min of decapitation ischemia compared with controls, to explore the degradation of the mitochondrial membrane and its relation to dysfunction of mitochondria. Activities of respiratory functions and respiratory enzymes (cytochrome c oxidase; F0F1‐ATPase) decreased significantly during ischemia. Considerable decreases in cardiolipin and phosphatidylinositol content were observed after 60 min, and other phospholipids showed similar but nonsignificant decreases in content. The amount of polyunsaturated fatty acid chains, such as arachidonic and docosahexaenoic acids, was reduced in each phospholipid, in some cases significantly, after 30 and 60 min of ischemia in time‐dependent manners. Degradation of mitochondrial phospholipids during ischemia associated with the deterioration of mitochondrial respiratory functions suggested the significance of such changes in phospholipid content in disintegration of cellular energy metabolism during cerebral ischemia.

Mechanism of intracranial rebleeding in Moyamoya disease

Intracranial hemorrhage is the major catastrophic event in the natural course of Moyamoya disease, and outcome of the patients with rebleeding is very poor. However, the mechanism underlying intracranial rebleeding is not well elucidated. We retrospectively analyzed 15 patients who bled two times or more among 46 bled patients with Moyamoya disease. The results indicated that there were two different types in the manner of rebleeding. One group consisted of seven cases, which bled two times or more at the same site than the original bleeding site. In four of these seven cases, a ruptured aneurysm was identified at the distal part of collateral vessel or on the major vessel. In the other three cases, no source of bleeding was identified. In all of these cases, rebleeding occurred within 2 months after the initial insult except for one case. Another group consisted of eight cases, which bled repeatedly but at different sites from the initial bleeding site. In any of these cases, neither aneurysms nor other vascular abnormalities were identified. In all of these cases, rebleeding occurred more than 2 months after the initial bleeding. The present result indicated that intracranial bleeding might occur as a result of rupture of a tiny aneurysm at the periphery of collateral vessels. These aneurysms may be blown out after initial bleeding. When they persist after the event, they may rupture again in a fairly short interval. In other cases, bleeding occur at different sites from the initial site. They are considered to be a result of ruptured weak Moyamoya vessels which are forced to act as collateral pathways and are under unusually increased hemodynamic stress.

Ruptured aneurysm of the posterior spinal artery of the upper cervical spinal cord: case report.

A case of aneurysm of the posterior spinal artery of the upper cervical spinal cord is presented. The patient had severe intracranial subarachnoid hemorrhage with disturbance of consciousness. Four-vessel angiograms showed neither anomalous arrangement of the arteries nor arteriovenous malformation intracranially or in the spinal subarachnoid space. Operation disclosed a thrombosed aneurysm of the posterior spinal artery, which was radically excised and histologically examined.