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

Nimodipine shws promise in the prevention and treatment of brain ischemia. We examined the interaction of nimodipine pretreatment in a dose sufficient to prevent postischemic hypoperfusion and hyperventilation. We studied four groups of rats: normocarbia plus vehicle (Group 1, n = 5), hypocarbia plus vehicle (Group 2, n = 4), normocarbia plus nimodipine (Group 3, n = 7), and hypocarbia plus nimodipine (Group 4, n = 6). Groups 3 and 4 received 1 mg/kg i.p. nimodipine, and Groups 1 and 2 received an equivalent amount of vehicle. Ventilation was left unaltered in Groups 1 and 3 or increased to lower PaCO2 to 21-24 mm Hg in Groups 2 and 4. Determination of regional cerebral glucose utilization (rCGU) was carried out using the [3H]2-deoxyglucose method, and regional cerebral blood flow (rCBF) was determined by the indicator fractionation method using [14C]iodoantipyrine. The brain regions studied were the cerebral hemispheres, the diencephalon, the cerebellum, and the brainstem. Hyperventilation in Groups 2 and 4 from approximately 38 to 22 mm Hg reduced rCBF to 60% of normocarbic levels (p less than 0.05). The slope and intercept of this response were similar in vehicle- and nimodipine-pretreated rats. Nimodipine modestly decreased mean arterial blood pressure by 20% and increased plasma glucose concentration by 60% (p less than 0.05). Although nimodipine tended to increase rCBF and decrease regional cerebrovascular resistance (rCVR), this was significant only for hemispheric rCVR (p less than 0.05). There was a borderline effect for nimodipine to increase rCGU, especially during hypocarbia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nimodipine on cerebral blood flow and metabolism in rats during hyperventilation. 291 16

Ischemic deporalization of cell membranes is associated with a precipitous influx of calcium from the extracellular to the intracellular compartment, and it is suggested that increased intracellular calcium in ischemic brain leads to an activation of phospholipase and to increase of the concentration of free fatty acids, in particular arachidonic acid, with energy depletion. The objective of the present study is to test whether calcium entry blocker, nimodipine, prevent increase of free fatty acids and metabolic disturbances during ischemic period, and promote functional and metabolic recovery after recirculation. Severe forebrain ischemia in rats was induced by four-vessel occlusion with reducing the systolic arterial pressure to 100 mmHg. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps of bilateral common carotid arteries and by increasing systemic blood pressure to the preischemic level. The EEG was continuously recorded from gold-coated screws inserted bilaterally in the parietal bones with the tips in extradural position, against a reference inserted prefrontal bone. Analysis of power spectrum of EEG activity was done by Berg Fourier Analyser. The brain were frozen in situ with liquid nitrogen before, during and after ischemia and then chiselled out during irrigation with liquid nitrogen. Concentrations of ATP, ADP, AMP and free fatty acids in brain tissue were determined with high performance liquid chromatography. Nimodipine, 10 micrograms/kg, was given intravenously 2-3 minutes before induction of ischemia, and an infusion of 1 microgram/kg/min was continued during ischemic and postischemic periods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of calcium entry blocker, nimodipine, on the cerebral function and metabolic recovery following experimental cerebral ischemia]. 293 79

Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 micrograms kg-1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 microgram kg-1 min-1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min-1 100 g-1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min-1 100 g-1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min-1 100 g-1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome.
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PMID:Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog. 308 30

The major pharmacological findings with nimodipine reviewed in this chapter are summarized in TABLE 3. On the basis of these findings, the following conclusions appear to be justified: 1. Nimodipine is a 1,4-dihydropyridine with Ca2+ channel antagonist properties. It is more lipophilic than nifedipine and its distribution volume in the brain of rats is higher than that of nifedipine. 2. Nimodipine dilates cerebral vessels at considerably lower concentrations than required for dilatation of peripheral blood vessels. It can, therefore, improve cerebral blood flow at doses that do not reduce systemic arterial pressure. 3. Nimodipine inhibits 45Ca uptake into vascular smooth muscle and neuronal cells. 4. Nimodipine antagonized postischemic cerebral hypoperfusion in cats and prolonged life of stroke-prone spontaneously hypertensive (SH) rats at doses that have little if any effect on arterial blood pressure. 5. Nimodipine reduced neurological deficits in dogs and monkeys with global cerebral ischemia. In focal ischemia (MCA occlusion) nimodipine reduced infarct size and neurological deficits and normalized intracellular brain pH. 6. In addition to its cerebral vasodilator effect, nimodipine appears to have a direct neuronal action. The suggested evidence for the neuronal site of action of nimodipine includes: a. Presence of nimodipine binding sites in brain. b. Blockade by nimodipine of Ca2+ channels in single nerve cells and in endocrine cells under conditions of sustained depolarization. c. Interactions with centrally acting drugs. d. Effects on release of various neurotransmitters from neuronal tissue or endocrine cells. e. Demonstration of anticonvulsant action of nimodipine. f. Blockade of behavioral effects of Ca2+ channel agonists by calcium channel antagonists.
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PMID:Pharmacology of nimodipine. A review. 328 65

The author discusses the epidemiology, the diagnosis, the clinical and morphological aspects of cerebral vasospasm from his personal experience and a study of the literature. Prediction and diagnosis of vasospasm is possible by evaluation of the amount of blood on CT scan, measuring fibrin breakdown products in the CSF and the findings of early EEG and Transcranial Doppler Sonography. CBF measurement is helpful in following the process of ischemia and deciding the right moment for operation. Early surgery on cerebral aneurysms is advocated in order to prevent rebleeding and for early removal of blood clot from the basal cisterns. If vasospasm and ischemia do develop, energetic treatment with hypervolemia and induced hypertension can be started without fear of rebleeding. Prophylactic intravenous administration of Nimodipine is thought to be of real value. Since the introduction of early surgery by the author 80 patients have been operated within 3 days after S.A.H. The mortality was 11% and the morbidity 7.5%. Management mortality and morbidity for the total group of 209 patients with S.A.H. treated either medically or surgically were 23.5% and 6% respectively. If one excludes the 18 patients that died within 24 hours the mortality was 15.6%.
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PMID:[Vascular spasm and cerebral ischemia after meningeal hemorrhage caused by rupture of an aneurysm]. 351 64

Male Wistar rats were subjected to forebrain ischemia of 10 min duration by clamping both common carotid arteries and simultaneously lowering systemic blood pressure to 40 mm Hg by exsanguination. Recovery was achieved by removing the arterial clamps and reinfusing the blood. Cortical levels of high-energy phosphates and glycolytic substrates were determined enzymatically. Naftidrofuryl (10 or 20 mg/kg i.p.) or ketamine (5 mg/kg i.v.) were applied 30 min prior to the induction of ischemia. S(-)-Emopamil (4 mg/kg) or nimodipine (50 micrograms/kg) were administered by intravenous infusion over 30 min. Nimodipine and emopamil increased the blood glucose level and lowered preischemic blood pressure. Under control conditions, a tendency toward a higher cortical glucose level was observed in treated brains. Brain energy stores were exhausted after ischemia in control and treated animals to the same degree. Lactate levels, however, were higher in emopamil-treated animals. This effect was attributed to the elevated preischemic glucose levels. During the early recovery period, the restoration of high-energy phosphates was accelerated by both calcium entry blockers. Nimodipine and emopamil increased the levels of glucose and glucose-6-phosphate in the early postischemic period. Naftidrofuryl (10 mg/kg) increased the level of creatine-phosphate and ATP after 2 min of recovery. Naftidrofuryl (20 mg/kg) exerted no effect on cerebral energy metabolism, but considerably reduced postischemic blood pressure (possibly thereby masking its ameliorative action). Ketamine accelerated the postischemic restoration of high-energy phosphates. In the conscious rat, local cerebral blood flow (LCBF) was determined with the 14C-iodoantipyrine technique following emopamil (20 mg/kg s.c.) or naftidrofuryl (10 mg/kg i.v.) application.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of cerebroprotective agents on cerebral blood flow and on postischemic energy metabolism in the rat brain. 361 Dec 6

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs. 365 2

The gerbil model was used to assess the therapeutic effects of the calcium antagonist nimodipine on cerebral ischemia. Transient cerebral ischemia was produced in each gerbil by bilateral common carotid occlusion of 10-, 15- or 20-min duration. Nimodipine (0.01 or 0.1 mg/kg) was administered intraperitoneally just before the carotid occlusion or 10-30 min after the removal of the arterial clips. Morbidity of each animal was evaluated using the stroke index, and the sum of stroke indices was calculated for evaluating the overall morbidity during a particular period of reperfusion. Mortality was observed for 24 hours after clip removal. Although, depending on the timing of the drug administration, the low-dose (0.01 mg/kg) nimodipine worsened the morbidity in the gerbils with 10-min ischemia, the high-dose (0.1 mg/kg) of the drug had a clear beneficial effect on the mortality associated with cerebral ischemia. These results are considered worthwhile for further trials to assess the usefulness of nimodipine as a therapeutic agent in the management of the acute ischemic stroke.
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PMID:The effect of the calcium antagonist nimodipine on the gerbil model of experimental cerebral ischemia. 373 60

Nimodipine, a calcium entry blocker, was administered in increasing doses of 0.1-3.0 micrograms kg-1 min-1 to six dogs after they had recovered consciousness from a surgical preparation that was conducted under general anesthesia and while they were under the influence of total spinal anesthesia. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Nimodipine did not influence either CBF or CMRO2. There was a decrease in the cortical pyruvate level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with six control dogs. It has previously been reported that nimodipine increases the CBF in global ischemia with a potentially beneficial effect on the neurological outcome. With no effect on normal CBF or metabolism, this suggests that nimodipine may be useful in a variety of ischemic situations without fear of either a steal phenomenon or untoward effects on intracranial pressure.
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PMID:The effects of nimodipine on cerebral blood flow and metabolism. 379 8

The normal rat spinal cord blood flow (SCBF) has been shown to increase after administration of nimodipine, a calcium channel blocker. The present study investigates the capability of nimodipine to improve SCBF, as measured by the hydrogen clearance technique, after a 53.0-gm clip compression injury to the T-1 segment of the rat spinal cord. The profound drop in mean systemic arterial blood pressure (MSAP) after cervical cord injury precluded any improvement in posttraumatic SCBF by nimodipine alone. Hence, in a randomized controlled study with five rats per group, pressor agents (whole blood, angiotensin, or adrenaline) were infused to maintain MSAP between 100 and 120 mm Hg after injury. Control animals received only a saline infusion. Nimodipine at the optimal dose found in normal animals (1.5 microgram/kg/min) was added to the pressor agents. The MSAP and other physiological parameters were measured in rats receiving the pressor agents only and in those receiving pressor agents combined with nimodipine. In rats receiving whole blood, angiotensin, or adrenaline the posttraumatic MSAP improved to between 100 and 120 mm Hg, but there was no improvement in SCBF compared to the saline group. The addition of nimodipine decreased MSAP and SCBF in all groups except those animals also receiving adrenaline, where the MSAP was maintained at 109 +/- 5 mm Hg. In these animals a significant increase in posttraumatic SCBF from 16.5 +/- 2.1 to 20.2 +/- 2.3 ml/100 gm/min (mean +/- standard error of the mean) occurred at the site of injury with the addition of nimodipine. The maintenance of an adequate MSAP by a pressor agent was crucial for nimodipine to improve posttraumatic SCBF by its ability to dilate the spinal vascular bed. Adrenaline was the only pressor agent that could fulfill the above criteria, although other pressor agents need to be investigated. Experiments are underway with the combination of adrenaline and nimodipine to further verify these encouraging results demonstrating an improvement in posttraumatic ischemia of the spinal cord.
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PMID:Effect of a calcium channel blocker on posttraumatic spinal cord blood flow. 381 38


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