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

The effects of nimodipine, a 1,4-dihydropyridine calcium channel blocker, on multiunit activity (MUA) of several brain structures were investigated in cats during 6 h immediately following acute global cerebral ischemia-anoxia induced by a 10 min cardiorespiratory arrest (CRA), as well as in cats exposed to sham procedures corresponding to CRA. Four groups of cats were studied: 1) CRA and continuous administration of nimodipine, 1 microgram/kg/min iv during 6 h; 2) CRA and continuous administration of vehicle; 3) sham and continuous administration of nimodipine as in group 1; 4) sham and vehicle as in group 2. MUA and electroencephalogram disappeared during ischemia-anoxia; their progressive recovery occurred throughout the hours following CRA, although 6 h after CRA MUA was still lower than its control prearrest values in all the recorded subcortical structures. Delta-like waves, isolated spikes, and bursts of fast EEG waves occurred during the recovery of EEG activity. Nimodipine inhibited the otherwise increasing MUA in mesencephalic reticular formation, hippocampus and putamen, but not in ventromedial hypothalamus, during the hours following acute global cerebral ischemia-anoxia. Absence of isolated spikes and bursts of fast EEG activity was noted in the EEG of CRA-, nimodipine-treated cats. Nimodipine significantly reduced MUA in hippocampus but not in other cerebral structures in cats of the sham treated group. The results suggest the involvement of 1,4 dihydropyridine sensitive calcium channels in the cellular mechanisms related to neuronal activity after cerebral ischemia-anoxia, and the possible relationship between the effects of nimodipine on MUA and better functional conditions of the central nervous system after acute global cerebral ischemia-anoxia.
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PMID:Effects of nimodipine on multiunit activity of several brain structures following acute global cerebral ischemia-anoxia in cats. 129 69

Using autoradiography, we have measured the in vivo binding of [3H]nimodipine to brain in a rat model of reversible cerebral ischemia. Ischemia was induced by simultaneous occlusion of the middle cerebral artery (MCA) and ipsilateral common carotid artery by microaneurysm clips. Rats were studied after 15 min of ischemia (ischemic group) or after 45 min of reperfusion following 15 min of ischemia (reperfused group). Regional cerebral blood flow (CBF) was determined autoradiographically using [14C]iodoantipyrine in both ischemic (n = 6) and reperfused (n = 6) groups. During ischemia blood flow in the territory of the MCA was depressed and recovered to normal only in the distal territory of the MCA following reperfusion. [3H]Nimodipine binding in the ischemic group (n = 12) was elevated in ischemic brain regions and declined significantly (p < 0.01) in these regions in the reperfused group (n = 11). The ratio of the volume of cortex showing increased binding to the total volume of the forebrain was 0.113 +/- 0.025 (mean +/- SD) in the ischemic group and declined to 0.080 +/- 0.027 following reperfusion (p < 0.005). In general, infarct was only observed in regions showing persistent elevation of nimodipine binding following reperfusion as determined by histology performed in a separate group of rats (n = 8) after 24 h of reperfusion. We conclude that increased nimodipine binding to ischemic tissue is initially reversible with prompt reestablishment of CBF and is a sensitive indicator of early and reversible ischemia-induced cerebral dysfunction.
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PMID:Reversibility of nimodipine binding to brain in transient cerebral ischemia. 140 19

In a controlled double blind experiment the influence of a continuous i.v. infusion of Nimodipine (1 microgram kg-1 min-1) upon infarct size, histopathology and neurological outcome in rats with permanent middle cerebral artery (MCA) occlusion was examined. The infusion was started 20 min. before the induction of ischemia and continued 4 hours thereafter. The nimodipine treated animals were subdivided into hypotensive (MABP lower than 85 mmHG for more than 5 minutes after arterial occlusion) and normotensive groups. Infarction size, documented by TTC, H&E and Nissl staining was significantly smaller (p less than 0.001) in nimodipine normtonic rats than the lesions in placebo and saline treated rats, as well as compared with hypotonic nimodipine animals (largest infarction). These differences were found to be entirely at the expense of the cortical (frontoparietal) component of the lesion, suggesting "penumbra" action of the drug. Moreover, nimodipine normotonic rats displayed lower cortical neuronal injury in the periinfarct zone. These findings were corroborated by corresponding better neurological scores. Our results indicate that nimodipine is effective in reducing focal cerebral ischemia, provided the MABP is maintained higher than 85 mmHg.
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PMID:[Effects of nimodipine in experimental permanent focal cerebral ischemia]. 141 81

Cerebral ischemia was induced in rabbits by selective injection of 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) into the left carotid artery. PMA provoked intravascular platelet and neutrophil aggregation. After PMA injection, a significant decrease in platelet and neutrophil counts was observed. Platelet and neutrophil emboli caused ischemia of the brain and brain barrier damage with accumulation of sodium fluorescein in the cerebrospinal fluid. Regional tissue analysis showed an ipsilateral alteration of the cerebral energy state and increased lactate levels. Pretreatment with the prostacyclin infusion completely blocked the alterations in both platelet and leukocytes counts and decreased the cerebral energy failure. Nimodipine administration decreased the changes in platelet and neutrophil counts and prevented the development of both brain barrier and cerebral energy failure. Nicergoline had no statistically significant beneficial effect on PMA-induced cerebrovascular injury.
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PMID:Effects of nimodipine and nicergoline on cerebrovascular injuries induced by activation of platelets and leukocytes in vivo. 146 72

We examined the effect of the calcium channel blocker nimodipine on postischemic hypoperfusion in the newborn piglet brain. A severe pneumothorax (SP) was induced by injecting air into the right thorax until the mean arterial blood pressure fell to 25% of baseline and was maintained for 4 min. Blood flow was immediately reduced 70-90% from baseline in each brain region during SP. In untreated animals postischemic hypoperfusion existed at 60 min, following recovery from SP with regional brain blood flow reduced 20-30% from baseline. Nimodipine infusion after SP prevented postischemic hypoperfusion in all brain regions and increased blood flows by as much as 40% above baseline in midbrain and brainstem structures. Nimodipine infusion began after severe brain ischemia prevented postischemic hypoperfusion and enhanced brain blood flow in this model.
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PMID:Effects of nimodipine on brain blood flow following acute brain ischemia in the newborn piglet. 148 64

The present prospective study, with participation of five of the six neurosurgical centers in Sweden, was conducted to evaluate the overall management results in patients with aneurysmal subarachnoid hemorrhage (SAH). The participating centers covered 6.93 million (81%) of Sweden's 8.59 million inhabitants. All patients with verified aneurysmal SAH admitted between June 1, 1989, and May 31, 1990, were included in this prospective study. A uniform management protocol was adopted involving ultra-early referral, earliest possible surgery, and aggressive anti-ischemic treatment. A total of 325 patients were admitted during the study period, 69% within 24 hours after hemorrhage. On admission, the patients were graded according to the scale of Hunt and Hess: 43 patients (13%) were classified in Grade I, 119 (37%) in Grade II, 53 (16%) in Grade III, 76 (23%) in Grade IV, and 34 (11%) in Grade V. Nimodipine was administered to 269 of the 325 patients: intravenously in 218, orally in 15, and intravenously followed by orally in 36. At follow-up examination 3 to 6 months after SAH, 183 patients (56%) were classified as having made a good neurological recovery, 73 patients (23%) suffered some morbidity, and 69 (21%) were dead. Surgery was performed in 276 (85%) of the patients; emergency surgery with evacuation of an associated intracerebral hematoma was carried out in 30 patients. Early surgery (within 72 hours after SAH) was performed in 170 individuals, intermediate surgery (between Days 4 and 6 post-SAH) in 29 patients, and late surgery (Day 7 or later after SAH) in 47 individuals. Of 145 patients with supratentorial aneurysms who were preoperatively in Hunt and Hess Grades I to III and who were treated within 72 hours, 81% made a good recovery; in 5.5% of patients, the unfavorable outcome was ascribed to delayed ischemia. It is concluded that, among patients with all clinical grades and aneurysmal locations, almost six of 10 SAH victims referred to a neurosurgical unit can be saved and can recover to a normal life.
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PMID:Overall outcome in aneurysmal subarachnoid hemorrhage. A prospective study from neurosurgical units in Sweden during a 1-year period. 156 33

The effects of the calcium channel blocker nimodipine and the non-competitive NMDA-antagonists MK-801 and phencyclidine (PCP) on infarct size 48 h after occlusion of the middle cerebral artery (MCA-O) were evaluated in the rat. Nimodipine was given at a dose of 0.3 mg/kg s.c. 30 min prior and 8, 16, and 24 h after MCA-O. MK-801 (1 mg/kg i.p. or 10 mg/kg i.p.) or PCP (0.3, 1.0, 3.0, 10, or 30 mg/kg i.p.) were administered 30 min prior to ischemia. In additional experiments 30 mg/kg PCP was given 1, 3, or 5 h post ischemia. Nimodipine and 1 mg/kg MK-801 reduced cortical infarct volumes significantly by 50% and 55%, respectively, while cortical infarct size fell by 32% and total infarct volume was not altered significantly after administration of 10 mg/kg MK-801. Pretreatment with 10 or 30 mg/kg PCP reduced cortical infarction by 47-53% and total infarct volumes by 39-42%. Posttreatment with PCP was effective if started at 1 or 3 h post ischemia.
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PMID:The effects of dizocilpine (MK-801), phencyclidine, and nimodipine on infarct size 48 h after middle cerebral artery occlusion in the rat. 191 95

The purpose of this study was to verify the possible involvement of nimodipine-sensitive calcium channels in ischemic Ca2+ influx to hippocampal neurons to assess their role in nimodipine neuroprotection. We induced 15-minute global cerebral ischemia in pentobarbital-anesthetized and relaxed rabbits, which had been implanted with a transhippocampal dialysis probe, by intrathoracic artery occlusion combined with hypotension. A part from electroencephalographic and morphologic observations, changes in the extracellular concentrations of calcium, amino acids, and blood-brain barrier permeability to fluorescein were detected by microdialysis of the hippocampus. Nimodipine was applied either intravenously or locally to the hippocampus before, during, and after ischemia. Application of nimodipine locally or systemically, which had no effect on extracellular amino acids, enhanced recovery and normalization of the electroencephalographic activity and protected hippocampal neurons from early morphologic changes. Intravenous nimodipine reduced the ischemia-evoked drop of extracellular Ca2+ and completely prevented postischemic leakage of the blood-brain barrier, whereas local nimodipine infusion did not modify these ischemic disturbances. Our results suggest that nimodipine-sensitive Ca2+ channels play a minor role in the ischemic calcium influx to hippocampal neurons. Nimodipine, apart from a potent vasotropic action, may also directly protect brain neurons by intracellular calcium antagonism rather than by inhibition of calcium influx.
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PMID:Diverse mechanisms of neuronal protection by nimodipine in experimental rabbit brain ischemia. 197 99

Many patients survive aneurysmal SAH with minimal neurological deficits, but are at risk for developing further neurological insult from ischemia resulting from cerebral vasospasm. Nimodipine has proven to be effective in preventing this complication in a majority of patients studied, with hypotension the most severe adverse effect. Nimodipine alone, or in combination with other methods of therapy, may significantly improve the neurological outcome in this select patient population.
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PMID:Nimodipine: the use of calcium antagonists to prevent vasospasm following subarachnoid hemorrhage. 214 68

We used laser-Doppler flowmetry to study the effect of nimodipine administered after the onset of focal cortical ischemia on regional cerebral blood flow in 16 halothane-anesthetized, mechanically ventilated Wistar rats. We selected the Wistar rats strain since it would provide a wide range of ischemia severities to test the vascular response to nimodipine. Laser-Doppler probes continuously recorded regional cerebral blood flow at two or three sites over the parietal cortex (dura intact) while brain temperature was regulated at 37 degrees C. Occlusion of the right middle cerebral and common carotid arteries reduced cerebral blood flow to a mean of 38% (range 13-77%) of baseline. Thirty minutes later, either 2 micrograms/kg/min nimodipine (n = 8) or its vehicle, polyethylene glycol 400 (n = 8), was administered by a continuous intravenous infusion. Over 60 minutes of treatment, both the nimodipine-treated and vehicle-treated groups showed a trivial (3%) mean increase in cerebral blood flow. Nimodipine failed to augment cerebral blood flow regardless of whether the cortex was severely, moderately, or mildly ischemic.
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PMID:Nimodipine posttreatment does not increase blood flow in rats with focal cortical ischemia. 220 48


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