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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

According to classic theory, a migraine attack is initiated by cerebrovascular spasm followed by extracranial vasodilatation. Results of recent studies support this theory and suggest that cerebral blood flow during the initial phase of migraine symptoms is, in fact, decreased and this decrease probably leads to ischemia and hypoxia. Cellular hypoxia, in turn, can cause an increase in the flow of calcium from the extracellular fluid to the intracellular space, resulting in calcium overload and cellular dysfunction. Because calcium-channel blockers selectively inhibit the intracellular influx of calcium ions, investigators have begun evaluating the efficacy of these agents for migraine prophylaxis. Nimodipine, a calcium-channel blocker that exhibits selective effects on cerebral vessels, seems to offer protection against the cerebral ischemia and hypoxia presumed to be operative during migraine attacks. In a double-blind, placebo-controlled study, nimodipine decreased the frequency and duration of migraine attacks by at least half in 69% of patients treated with this agent. Comparable reductions in migraine frequency and duration were attained in 58, 51, 41 and 52% of patients treated with methysergide maleate, pizotifen, clonidine hydrochloride and propranolol, respectively. The piperazine derivative flunarizine also has calcium-channel blocking properties. This agent prevents vasospasm in cerebral arteries and protects against cerebral hypoxia. Results of double-blind studies of migraine prophylaxis with flunarizine demonstrate the beneficial effects of this agent, particularly in younger patients. Flunarizine proved to be superior to pizotifen in decreasing the severity of migraine attacks and comparable to pizotifen in decreasing their frequency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium-channel blockers in the treatment of migraine. 388 6

Nimodipine, a calcium channel blocker, is known to increase cerebral blood flow. In the present study, the authors investigated the effect of nimodipine on spinal cord blood flow in normal rats. Cardiovascular parameters, including mean systemic arterial blood pressure, cardiac output, and heart rate, were recorded during infusion of nimodipine in a dose-response fashion. The experiment was a randomized blind study in which four groups of five rats received different doses of nimodipine (0.001, 0.01, 0.05, and 0.10 mg/kg) intravenously over 30 minutes, and a control group of five rats received only the diluent. The hydrogen clearance and thermodilution techniques were used to measure spinal cord blood flow and cardiac output, respectively. The 0.05-mg/kg dose of nimodipine caused the largest increase in spinal cord blood flow, with a 40% increase over the preinfusion level, although there was a 25% reduction in mean arterial pressure. The 0.10-mg/kg dose did not increase spinal cord blood flow more than the 0.05-mg/kg dose, most likely due to the concomitant 37% reduction in mean arterial pressure. Cardiac output was significantly increased by the 0.05- and 0.10-mg/kg doses secondary to the drop in total peripheral resistance. The increase in spinal cord blood flow produced by nimodipine lasted approximately 20 minutes after the termination of the infusion. Thus, nimodipine at a dose of 0.05 mg/kg markedly increased blood flow in the normal spinal cord even though there were major changes in mean systemic arterial pressure and cardiac output. Further research is required to determine whether this drug might be beneficial in treating ischemic states of the spinal cord, such as posttraumatic ischemia.
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PMID:Increase in rat spinal cord blood flow with the calcium channel blocker, nimodipine. 392 62

The potent, centrally active, calcium channel antagonist, nimodipine, was utilized in a highly predictive "spinal stroke" model in order to investigate the potential pathophysiological effects of calcium flux in spinal injury, as well as to evaluate the potential therapeutic role of the newly developed dihydropyridine derivatives in ischemic central nervous system injury. Nimodipine, administered before or after ischemia, at doses shown to be effective in improving cerebral blood flow and in dilating central blood vessels, failed to improve either the histopathological changes or the functional deficit caused by temporary aortic occlusion in the unanesthetized rabbit.
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PMID:Evaluation of the calcium channel antagonist nimodipine in experimental spinal cord ischemia. 670 49

Ten minutes of complete ischemia was produced in 11 dogs by temporary ligation of the aorta. Immediately before the ischemic episode, the dogs received nimodipine, a new calcium entry blocker, 10 micrograms kg-1, i.v., followed by an infusion of 1 microgram kg-1 min-1 for 2 h. Post-ischemic cerebral blood flow and metabolism were measured for 120 min in six dogs. Neurologic recovery was evaluated 48 h post-ischemia in five dogs. The results were compared to previously determined controls. Nimodipine nearly doubled cerebral blood flow in the delayed post-ischemic hypoperfusion period, compared to untreated dogs (approximately 45% versus 25% of pre-ischemic control values), but had no significant effect on metabolism. Nimodipine also improved neurologic recovery. Four of five treated dogs were normal and one was moderately damaged, whereas six of seven controls were either severely damaged or dead. This suggests that the delayed hypoperfusion state occurring after complete cerebral ischemia probably does contribute to the ultimate neurologic damage, and that nimodipine offers a potential protective effect.
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PMID:Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. 682 16

Post traumatic ischemia appears to be largely involved for the extension of lesions in acute injury of the spinal cord. The present study evaluate the putative improvement of spinal cord blood flow (S.C.B.F.) by calcium channel blocker after acute spinal cord injury in baboons. S.C.B.F. measured by a scannographic technique with 133Xe were realised each thirty min for 4 hours and seven days later; somatosensory evoked potentials (S.E.P.) magnetic resonance imaging (M.R.I.) and histological study of the spine were realised at different time of the experimentation. Ten monkey were used. Acute trauma was achieved by compression of the cord at T1 by applying a 2.10(2) kPa (2 bar) pressure for 5 s with a balloon catheter inflated with Ringer's solution. Then, five monkeys received saline infusion for seven days and the other five received a nimodipine infusion (0.04 mg.kg-1.h-1) during the same time. Nimodipine improved significantly S.C.B.F. Two monkeys in the treated group showed improvement of axonal function as judged by S.E.P. Conversely no significant difference was noted by R.M.I. although the histological study showed smaller lesions in the treated group. Nimodipine could represent in the next years a new medical treatment in acute spinal cord injury in man.
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PMID:[Medical treatment of spinal cord injury during the acute phase. Effect of a calcium inhibitor]. 780 54

In this prospective study we report the outcome for all patients with a verified aneurysmal SAH managed at the Department of Neurosurgery at the University Hospital in Lund, Sweden during the four-year span from June 1, 1989 to May 31, 1993. A total of 275 patients were admitted during the study period. The vast majority of patients (196 individuals, i.e. 71%) was admitted within 24 h after the bleed. Mean age was 54.3 years and the female/male ratio 1.8/1. Nimodipine was administered in 231 (84%) of the 275 patients. We clipped the ruptured aneurysm in 199 patients. At follow-up 3 months after the bleed 161 patients were classified as having made a good neurological recovery (59%). The morbidity was 20% and 59 patients (21%) had died. The overwhelming cause for morbidity and mortality was damage from the initial bleed (62 patients, 23%). Notably, considering morbidity and mortality, delayed ischemia was less frequent than both surgical complications and rebleeding, respectively. Of the 275 patients, 13 (5%) patients made an unfavorable outcome due to delayed ischemic deterioration. There was a strict correlation between the initial clinical condition and final outcome. Of 51 grade V patients, only 2 made a good recovery. There was also a strict correlation between the amount of extravasated blood and outcome. There was no difference in clinical outcome between patients with arterial hypertension versus normotensive individuals. The mortality rate was worse for posterior circulation aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Which are the major determinants for outcome in aneurysmal subarachnoid hemorrhage? A prospective total management study from a strictly unselected series. 783 9

Adenosine is now widely accepted as the major inhibitory neuromodulator in the central nervous system besides GABA. It has been suggested to be an endogenous neuroprotective metabolite. In situations of metabolic stress, e.g. ischemia adenosine decreases energy demand and increases energy supply. Of particular relevance in this context is its modulation of glutamate release. A shift of this adenosine-glutamate balance in favor of adenosine helps to restore function at the cellular, organ and organism level. Adenosine A1 receptor agonists and metabolic inhibitors, e.g. of transport, deaminase and xanthine oxidase have been demonstrated to be effective in different animal models of ischemia. Nimodipine, a L-type channel calcium antagonist currently in clinical trials for stroke and dementia syndromes, has now been shown to be a potent adenosine transport inhibitor in clinically relevant concentrations. Increase of adenosinergic neuromodulation may well be one of several future therapeutic strategies in neuroprotection.
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PMID:Adenosine--an endogenous neuroprotective metabolite and neuromodulator. 788 4

Toxic oxidants (oxygen free radicals) have been implicated in the formation of brain edema from ischemia-reperfusion injury or tumor growth. We investigated the ability of an iron chelator, a calcium channel blocker, and a xanthine oxidase inhibitor to reduce formation of brain edema following a cold lesion in cats. The agents were given independently of each other in an attempt to inhibit the Haber-Weiss reaction, prevent Ca++ modulated uncoupling of oxidative phosphorylation, and inhibit the generation of toxic oxidants via xanthine oxidase, respectively. Pentastarch-deferoxamine conjugate at a dose of 50 mg/kg was given 15 minutes before and 60 minutes after the cold lesion. Nimodipine was given at a dose of 1 mg/kg 1 hour before and 2 hours after the cold lesion. Allopurinol was given at a dose of 50 mg/kg 24 hours before, at the time of the lesion and, 24 and 48 hours after the lesion. Gravimetric measurements of multiple brain areas were performed at 24 hours post-lesion in the pentastarch-deferoxamine and nimodipine groups and at 72 hours post-lesion in the allopurinol group. None of these agents led to significant reduction in brain edema formation as measured with a gravimetric column of kerosene and bromobenzene. Pentastarch-deferoxamine conjugate was utilized to avoid the confounding effects of arterial hypotension which is seen with intravenous deferoxamine. There was even a suggestion of increased edema in the periventricular white matter in animals treated with nimodipine. Taken together, independent inhibition of the Haber-Weiss reaction, of calcium channels, or of xanthine oxidase does not reduce formation of brain edema in the cold lesion model.
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PMID:Proposed toxic oxidant inhibitors fail to reduce brain edema. 797 65

To examine the role of calcium influx in the early phase after brief forebrain ischemia and subsequent delayed neuronal cell death in the hippocampus, 45Ca autoradiography and electron microscopic cytochemistry, by a combined oxalate-pyroantimonate method, were carried out in gerbil brains after 5 min bilateral common carotid arterial occlusion. Further, neuronal damage during the ischemic and postischemic periods was determined by conventional or immunohistochemical staining for microtubule-associated protein 2 (MAP2) with and without calcium-entry blockers. 45Ca autoradiography showed a high peak of calcium in the hippocampus at 5 min of recirculation. Electron cytochemical microscopy also demonstrated accumulation of intracellular calcium pyroantimonate deposits in the neuronal cells in all regions. At 30 min of reperfusion, amounts of calcium in the hippocampus returned to the control levels, and intracellular dense calcium pyroantimonate deposits were reduced in these areas. Loss of the reaction for MAP2 was noted in the medial CA1 of the hippocampus immediately after 5 min ischemia and at 5 and 30 min after reperfusion. MK-801 (10 mg kg-1), an N-methyl-D-aspartate (NMDA) receptor antagonist, injected intraperitoneally 1 h before ischemia, suppressed the early increase of calcium in the forebrain and neuronal cell necrosis in the CA1. However, neither injection of MK-801 30 min after reperfusion nor preischemic treatment with 0.5 mg kg-1 Nimodipine or 1 mg kg-1 Nicardipine, voltage-sensitive calcium channel antagonists, prevented neuronal death. In immunohistochemical staining for MAP2, the ischemic lesion in the medial CA1 maintained after 5 min ischemia and the subsequent early reperfusion period in the untreated brains was protected by the preischemic injection of 10 mg kg-1 MK-801, but was not restored by the injection of 0.5 mg kg-1 Nimodipine or 1 mg kg-1 Nicardipine. In conclusion, it is suggested that an early excess of calcium influx could be caused mainly by excitatory amino acid overload through NMDA receptor-mediated calcium channels during the ischemic and early postischemic periods.
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PMID:The role of early Ca2+ influx in the pathogenesis of delayed neuronal death after brief forebrain ischemia in gerbils. 818 66

Over a seven-year period, 130 patients with delayed ischaemia after cerebral aneurysm haemorrhage were treated with intravenous nimodipine. The delay from the last haemorrhage to the appearance of ischaemic symptoms was one to 18 days, and vasospasm was confirmed in most cases. Nimodipine treatment was started within three days of delayed ischaemic deficit (DID) onset, at a low dose increased quickly to 30-45 ug/kg/hr, and reduced gradually over the last day or two of the course. The duration of treatment was one to 27 days. Side effects were minor, and serious complications few. Hypotension occurred in 35 cases. During treatment, there were highly significant improvements in both clinical grade and Glasgow Coma Score. The final outcome was 98 good (Glasgow Outcome Score 1), 18 permanent deficits (eight GOS 2, ten GOS 3), and 14 dead. Ischaemia was directly involved in only half the deaths. These results are much better than the natural history (about 1/3 dead and 1/3 disabled), and a considerable improvement over fluid and hypertensive treatment (17% dead, 29% deficits), calculated from a literature review. Nimodipine is also safer than induced hypertension, especially pre-operatively.
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PMID:Treatment of symptomatic vasospasm with nimodipine. 821 89


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