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

Calcium channel blockers constitute a very important group of drugs that are commonly used in the treatment of cardiovascular and cerebrovascular disorders. Current indications for these medications include hypertension, angina, supraventricular arrhythmias, and prevention of coronary and cerebral vasospasm. Although calcium channel blockers originally held great promise in the treatment of myocardial and cerebral ischemia, clinical results have been discouraging. An understanding of the basic physiological mechanisms of actions for these drugs is important for the practising clinician and may explain the disappointing results for the treatment of ischemia to date. This paper is a narrative review, from a clinician's viewpoint, of the structure and role of calcium channels in cardiac and cerebrovascular tissues, as well as a review of the in vitro and clinical results of calcium channel blockade in myocardial and cerebral ischemia.
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PMID:Calcium channel blockers in myocardial and cerebral ischemia: a clinician's review from bench to bedside. 1020 97

Delayed cerebral vasospasm after aneurysm rupture is one of the major complications of subarachnoid hemorrhage. The purpose of this review was to determine the true incidence of vasospasm. All literature on cerebral aneurysms from 1960 onwards was reviewed, and the figures extracted from publications that mentioned vasospasm. Angiographic vasospasm, where patients were studied at the time of peak incidence, was reported in about two thirds of cases. Symptomatic vasospasm or delayed ischemia affects about one third. Untreated, nearly a third of those with ischemic deficits die and a similar proportion are left permanently disabled. Variations of Triple-H (hypervolemia, hypertension, hemodilution) therapy, used early after hemorrhage for prophylaxis of vasospasm, are associated with a decrease of nearly half in the incidence of delayed ischemia. When used as therapy outcome also appears better, with a reduction particularly in the death rate. Calcium antagonists have been widely used, especially nimodipine. In several controlled trials the incidence of delayed ischemia was significantly reduced. More importantly, the overall outcome of all subarachnoid hemorrhage patients was better with nimodipine prophylaxis. The 21-aminosteroid tirilazad mesylate has been the subject of several trials. In one the overall outcome of all patients was improved, but the effect was essentially in males only. Further studies with larger doses in females are being analyzed.
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PMID:The effect and management of delayed vasospasm after aneurysmal subarachnoid hemorrhage. 1023 99

Although the major focus of recent cerebral protection research has been aimed at developing receptor-specific drugs, this effort has currently resulted in few improvements in patient outcome. Until advances in pharmacology translate to improvements in humans, the clinician and his patients will be well served by using more traditional techniques to prevent and treat cerebral ischemic events. This approach will involve interventions to a) identify patients who are experiencing or are at risk for developing cerebral ischemia, and b) alter systemic physiology in an attempt to lessen the duration and severity of any ischemic insults. Initial therapy should include interventions to improve cerebral perfusion and the oxygen carrying capacity of the blood. Once this is accomplished, measures should be taken to control blood glucose concentrations and treat fever. In otherwise stable surgical patients, mild reductions in patient temperature also may be of benefit, provided the temperature reductions do not introduce problems in systemic physiology and the patient is rewarmed prior to awakening from general anesthesia. General anesthetic choice may be of importance in controlling intracranial pressure and seizure activity; however, if direct cerebral protection is desired, the anesthetic of choice should be a barbiturate. Finally, in the patient at risk for cerebral vasospasm, nimodipine treatment should be considered. Collectively, these interventions should increase the patient's chance for optimal neurologic recovery following ischemia.
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PMID:The prevention and treatment of cerebral ischemia. 1037 Aug 30

The pathogenesis of cortical blindness as a rare complication in severe preeclampsia is still unclear. The case of a women with postpartum blindness is reported in which CT and MRI initially showed cortical and subcortical edema in the parieto-occipital lobes. At this time cerebral angiography and transcranial color-coded sonography (TCCS) revealed widespread cerebral vasospasm. Mean blood flow velocities in the middle and posterior cerebral artery and carotid syphon initially reached 380 cm/s and normalized within 2 weeks. While the patient's vision improved rapidly, follow-up MRI disclosed ischemic lesions and petechial hemorrhage in the occipital cortex. This case provides rare documentation that transient blindness in patients with preeclampsia may result from parieto-occipital ischemia due to cerebral vasospasm. In such patients TCCS may be useful to detect vasospasm associated with preeclampsia/eclampsia.
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PMID:[Transient cortical blindness in EPH gestosis caused by cerebral vasospasm]. 1055 88

Some of the neurological deficits that emerge after aneurysmal subarachnoid hemorrhage (SAH) in humans are presumably caused by ischemic brain damage consequential to SAH-induced delayed cerebral vasospasm. This vasospasm probably results from an imbalance among vasoactive factors released from both the clot formed by extravasated blood and adjacent tissues, and in particular from a decrease in the endothelium-derived relaxing factor nitric oxide (NO). Brain ischemia is also known to elevate brain production and deposition of beta-amyloid, and to induce a delayed increase in total NO synthase (NOS) activity due to induction of expression of so-called induced NOS isoform, phenomena that may secondarily contribute to SAH-related brain damage. The aim of this study was to investigate the effects of treatment with the intracellular NO donor hydroxylamine on: (i) basilar arterial wall that remained in a direct contact with the clot, (ii) formation of the beta-amyloid precursor protein (beta-APP), (iii) total brain NOS activity, and (iv) neurological outcome in a 'two-hemorrhage' rat SAH model. Intraperitoneal (i.p.) administration of 0.18 mmol/kg hydroxylamine hydrochloride (12.5 mg/kg) twice daily for 7 days beginning immediately after the first 'hemorrhage' (intracisternal blood injection) reduced basilar arterial wall damage and attenuated post-SAH neurological deficit. It also reduced the SAH-related increases in hippocampal and cortical beta-APP immunoreactivities and hippocampal NOS activity measured 24 h after commencement of the treatment. These results indicate that intracellular NO donors that yield NO through the action of widely distributed enzymes in brain cells (cytochromes, catalase) can attenuate detrimental effects of SAH.
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PMID:Hydroxylamine attenuates the effects of simulated subarachnoid hemorrhage in the rat brain and improves neurological outcome. 1062 68

Syndromes of intracranial hemorrhage, and particularly subarachnoidal, i.e., intracerebral hemorrhage (SAH and IH) present clinical entities that are the most severe conditions in neurology. Timely recognition, diagnosis and adequate therapy are imperative. The most important factor that aggravates an already difficult prognosis of those entities is cerebral vasospasm. Upon the presented facts, the aim of this investigation was to establish the value and role of administration of selective calcium channel blocker--nimodipine in patients with SAH and IH compared to the degree of neurological and functional impairment, as well as the recovery of the function of consciousness compared to the patients with those syndromes from an earlier period, who were not treated with this medicament. Investigation comprised 30 patients who received nimodipine and 20 patients without this agent in therapeutic program. Results of the investigation confirmed significant difference concerning the neurological recovery, improvement of functional capability and recovery or consciousness disturbances, respectively, in patients who received nimodipine compared to the group without this agent. It can be concluded that nimodipine as calcium channel blocker with multitopic pharmacological effects on mechanism of SAH or IH development, respectively, as well as on the development of complications of those syndromes, particularly to the development of vasospasm and reactive ischemia, with the improvement of hemorrheologic disorders deserves to be included as the unavoidable segment of therapeutic program of SAH and IH syndrome immediately after clinical phenomenology is revealed.
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PMID:[Role of nimodipine in the therapy of subarachnoid and intracerebral hemorrhage]. 1070 8

Retrospectively, subarachnoidal hemorrhage can be misdiagnosed when the acute event did not bring the patient to medical attention, when clinical history is unclear and the CT scan is normal. Moreover, days after subarachnoid hemorrhage, cerebral vasospasm can result in neurological deficits that are indistinguishable from that produced by other causes of stroke. We report our experience with two patients who presented with symptoms of ischemia due to an arterial vasospasm that followed unrecognized rupture of an intracranial aneurysm. In both cases, CT scan failed to detect subarachnoid hemorrhage while MR detected the presence of signal changes in the subarachnoidal spaces associated with an ischemic stroke in one case. Neurological symptoms resolved completely after aneurysm treatment. MR can be a critical for the diagnosis of stroke secondary to vasospasm in order to prescribe an adapted treatment, avoid anticoagulant or thrombolytic therapy, and rapidly exclude the recently ruptured aneurysm to protect the patient from the risk of rebleeding.
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PMID:[The value of MRI for the diagnosis of meningeal hemorrhage during vasospasm]. 1078 53

Diazeniumdiolates are compounds containing the X-[N(O)NO](-) structural unit that as a class offer many advantages as tools for probing the roles of nitric oxide (NO) in biological redox processes. Available examples in which X is a secondary amine group spontaneously generate up to two molecules of NO per [N(O)NO](-) unit when dissolved in aqueous media; their half-lives range from 2 s (for X = L-prolyl) to 20 h [for X = (H(2)NCH(2)CH(2))(2)N] at pH 7. 4 and 37 degrees C, and are in general relatively little influenced by medium effects or metabolism. When X = O(-) (Angeli's salt), first-order dissociation produces NO(-) rather than NO, but the ion becomes an NO source on 1-electron oxidation; diazeniumdiolate-derived NO can also be used to generate reactive nitrogen/oxygen species with higher nitrogen oxidation states (+3 and +4) in the presence of selected oxidizing agents. The advantages of diazeniumdiolates in biomedical research are briefly illustrated with examples from the recent literature probing NO's role in inhibiting oxidative drug metabolism, radical-induced lipid oxidation, the cytotoxicity of reactive oxygen species, and ischemia-induced vascular reoxygenation injury. Future work with this compound class should provide further insight into the mechanisms of NO's involvement in pro- and antioxidant processes, and may well lead to important medicinal advances, including reversal of cerebral vasospasm and radiosensitization of hypoxic tumors.
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PMID:Diazeniumdiolates: pro- and antioxidant applications of the "NONOates". 1092 70

Over-activation of calpain, a ubiquitous calcium-sensitive protease, has been linked to a variety of degenerative conditions in the brain and several other tissues. Dozens of substrates for calpain have been identified and several of these have been used to measure activation of the protease in the context of experimentally induced and naturally occurring pathologies. Calpain-mediated cleavage of the cytoskeletal protein spectrin, in particular, results in a set of large breakdown products (BDPs) that are unique in that they are unusually stable. Over the last 15 years, measurements of BDPs in experimental models of stroke-type excitotoxicity, hypoxia/ischemia, vasospasm, epilepsy, toxin exposure, brain injury, kidney malfunction, and genetic defects, have established that calpain activation is an early and causal event in the degeneration that ensues from acute, definable insults. The BDPs also have been found to increase with normal ageing and in patients with Alzheimer's disease, and the calpain activity may be involved in related apoptotic processes in conjunction with the caspase family of proteases. Thus, it has become increasingly clear that regardless of the mode of disturbance in calcium homeostasis or the cell type involved, calpain is critical to the development of pathology and therefore a distinct and powerful therapeutic target. The recent development of antibodies that recognize the site at which spectrin is cleaved has greatly facilitated the temporal and spatial resolution of calpain activation in situ. Accordingly, sensitive spectrin breakdown assays now are utilized to identify potential toxic side-effects of compounds and to develop calpain inhibitors for a wide range of indications including stroke, cerebral vasospasm, and kidney failure.
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PMID:The pathogenic activation of calpain: a marker and mediator of cellular toxicity and disease states. 1116 79

Mild hypothermia (32-34 degrees C of brain temperature) was used for brain protection in patients with progressive ischemic neurological deficits associated with severe cerebral vasospasm and who did not respond to medical treatment or intravascular angioplasty. Results showed that 2 of 3 patients in Hunt & Kosnik grade I to III and 2 patients who underwent delayed operation on day 5 and 9 each and had ischemic neurological deficits made good recovery with this treatment. Favourable outcome was obtained in 4 of 9 patients in grade IV and V. Mild hypothermia is thought to provide brain protection in critical ischemia due to severe cerebral vasospasm and can lengthen therapeutic time to employ angioplasty and intraarterial Papaverin infusion.
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PMID:Protective effect of mild hypothermia on symptomatic vasospasm: a preliminary report. 1145 87


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