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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery disease pathophysiology and platelet physiology are summarized, and the use of antiplatelet drugs in coronary artery disease is reviewed. Aspirin, sulfinpyrazone, and most other nonsteroidal anti-inflammatory agents alter platelet function by inhibiting the activity of cyclooxygenase, an enzyme necessary for the production of prostaglandins. Drugs that inhibit thromboxane synthetase or antagonize thromboxane A2 at the receptor level are under investigation. Prostacyclin and dipyridamole inhibit platelet function by elevating the concentration of cyclic AMP in platelets, but proof of their efficacy is limited. Most clinical trials of antiplatelet drugs in coronary artery disease have been small and of short duration; many have demonstrated short-term benefits, but long-term benefits are less obvious. Retrospective studies of patients before initial myocardial infarction suggest that regular aspirin ingestion may reduce the occurrence of cardiovascular complications. In prospective trials, the benefit of aspirin therapy for primary prevention of coronary artery disease was balanced by an increased likelihood of stroke. For secondary--after initial infarction--prevention of cardiovascular complications, the administration of aspirin and other antiplatelet agents has consistently decreased the rate of nonfatal myocardial infarction, overall mortality, or both. In the Second International Study of Infarct Survival, patients treated with streptokinase plus aspirin showed the greatest reduction in mortality, while each drug alone was associated with significantly lower mortality than placebo. Aspirin may improve clinical outcome in patients with or without previous myocardial infarction or with unstable angina pectoris. The daily dose should not exceed 325 mg. Antiplatelet therapy should not be used in patients at high risk for bleeding.
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PMID:Antiplatelet agents in coronary artery disease. 240 21

The laterofrontal (LF) cirri on isolated gill filaments of Mytilus edulis, prepared in natural seawater, are active and initially beat with an average frequency of about 8 Hz (with a range of 6-14 Hz). However, the lateral (L) cilia on these filaments are arrested in a position at the end of their recovery stroke. Perfusion of the filament with artificial seawater (ASW), with or without 1% ethanol, has little or no biological effect on the activity of the LF cirri, although a transitory decrease in frequency often accompanies the perfusion process. The L cilia remain arrested during perfusion with ASW. The exposure of the gill to low levels of 5-hydroxytryptamine (5HT) (10(-8) less than 5HT less than 10(-7) M) has no effect on the activity of the LF cirri but stimulates the L cilia to beat. Exposure to higher concentrations of 5HT (greater than 10(-7) M) elevates the beat frequency of the L cilia and simultaneously inhibits the activity of the LF cirri, leading to their arrest in a position at the end of the effective stroke. This arrest of the LF cirri occurs as the L cilia attain a 5HT-induced beat frequency between 12 to 14 Hz. The influence of 5HT on the L cilia and the LF cirri can be reversibly mimicked or enhanced by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). A concentration of 0.5 mM IBMX mimics low 5HT concentrations (about 10(-7) M) by stimulating the L cilia to beat without affecting the beat frequency of the LF cirri. A combination of 10(-7) M 5HT and 0.5 mM IBMX in ASW mimics high (greater than 10(-6) M) 5HT concentrations by arresting the LF cirri and increasing the beat frequency of the L cilia. Under these conditions, the threshold of the LF cirri arrest response is again found to occur as the L cilia attain a beat frequency of 12-14 Hz. These results suggest that the mechanisms of LF cirri arrest and L cilia activation are mediated by 5HT-induced changes in intracellular cyclic AMP levels.
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PMID:The antagonistic effects of 5-hydroxytryptamine and methylxanthine on the gill cilia of Mytilus edulis. 241 3

The localization and distribution of catecholamines, selected neuropeptides, and the cyclic nucleotide second messengers has been determined in the superior cervical ganglion of the stroke-prone variant of the spontaneously hypertensive rat (SHR) and its normotensive Wistar-kyoto (WKY) control. Significant alteration in the frequency of occurrence of dopaminergic small intensely fluorescent cell clusters was seen in the stroke-prone variant of the SHR. The immunofluorescent localization of cyclic AMP (cAMP) and cyclic GMP (cGMP) were also changed in the stroke-prone variant, as was the immunofluorescent staining quantity of the neuropeptides somatostatin and substance P. The morphological pattern of staining for the various compounds in the normotensive control (WKY) was equivalent to the Sprague-Dawley rat strain. The implications of the altered neurochemistry in the superior cervical ganglion on the high blood pressure, and the predisposition for stroke in this strain are discussed.
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PMID:Neurochemical differences in the superior cervical ganglion of the spontaneously hypertensive rat stroke-prone variant. 244 7

Disturbances in lipid metabolism may play an important role in the onset of irreversible myocardial damage. To investigate the effect of ischemia and reperfusion on lipid homeostasis and to delineate its possible consequences for myocardial damage, Krebs-Henseleit-perfused, working rat hearts were subjected to various periods of no-flow ischemia (10 to 90 minutes) with or without 30 minutes of reperfusion. During ischemia, the rise in nonesterified fatty acids (NEFAs) was preceded by the accumulation of substantial amounts of glycerol, indicating the presence of an active triacylglycerol-NEFA cycle. The subsequent rise in NEFAs (from 0.25 to 1.64 mumol/g dry residue wt after 90 minutes [means]) coincided with the reduction of ATP to values lower than 10 mumol/g dry wt and the rise of AMP, a potent inhibitor of acyl-coenzyme A synthetase, to values exceeding 2 mumol/g dry wt, making the latter compound a good candidate to hamper the turnover of endogenous lipids during prolonged ischemia. Reperfusion resulted in an additional rise in NEFAs (up to 4.1 mumol/g dry residue wt after 60 minutes of ischemia). Neither ischemia nor reperfusion resulted in significant decreases in the tissue content of triacylglycerols and the various phospholipids. During reperfusion recovery of stroke volume was still adequate at tissue NEFA levels thought to be incompatible with normal mitochondrial function. A positive correlation (r = 0.81) was found between NEFA content of reperfused hearts and cumulative release of lactate dehydrogenase during reperfusion. Accordingly it is concluded that 1) reperfusion results in additional changes in myocardial lipid homeostasis, 2) the accumulating NEFAs are compartmentalized, possibly at the cellular level, and 3) the accumulation of NEFAs is a sensitive marker for myocardial cell damage.
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PMID:Lipid alterations in isolated, working rat hearts during ischemia and reperfusion: its relation to myocardial damage. 278 64

Evidence has steadily accumulated to indicate that the rapid fluctuations in cyclic nucleotides during primary and secondary stroke are more than epiphenomena of the disease. During acute phases of ischemia, anoxia or hypoxia cyclic AMP rapidly accumulates in cerebral tissue, cerebrospinal fluid (CSF) and venous plasma, while cyclic GMP either remains unchanged or declines. The massive release of transmitters (catecholamines and adenosine) or ionic fluxes (Na+ and K+) may account for these observations. If reflow is established through a previously occluded vessel cyclic AMP content rises even higher in conjunction with a sharp rise in cyclic GMP. It is during this reflow period subsequent to longer term stroke (30-60 min) that the synaptic membrane enzyme, adenylate cyclase, is especially vulnerable. Presumably the cause of injury to cell membrane systems results from excess lactic acid accumulation and/or Ca++ entry through the damaged blood-brain barrier. The latter initiates breakdown of membrane phospholipids with resultant synthesis of vasoactive prostaglandins and formation of free radicals causing further insult to membrane phospholipids. Thus drugs acting to inhibit formation of prostaglandins, scavenge free radicals, reduce lactate formation, inhibit Ca++ entry or stabilize cell membranes have been shown to possess varying degrees of protective action toward adenylate cyclase. Moreover, cyclic AMP has been found to reverse stroke-induced vasospasm in central vessels. Reduced cyclic AMP content in CSF has been used to monitor the severity of coma, whereas clinical improvement was associated with predictable increases in the cyclic nucleotide. Therefore, cyclic nucleotides and related membrane enzyme systems might be used as target molecules in which to develop future therapeutic strategies for prevention or treatment of stroke.
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PMID:Cyclic nucleotides in stroke and related cerebrovascular disorders. 286 May 49

The discovery that monoamine nerves end on the central microvessels of the choroid plexus, pia-arachnoid and parenchyma has prompted an intense investigation as to their physiological and neuropathological roles. The source of the monoamine fibers to the pial vessels and choroid plexus was shown to be the superior cervical ganglion. Ganglionic stimulation causes vasoconstriction or vasodilation of pial vessels, an event depending upon the functional ratio of alpha to beta adrenergic receptors. Moreover, stimulation of the superior cervical ganglion evokes an inhibition of cerebrospinal fluid formation in choroid plexus. The locus coeruleus is the site of adrenergic nerve supply to the parenchymal capillaries and stimulation of this nucleus increases capillary permeability to small molecules and water. Neurotransmitter receptors (adrenergic, histamine, adenosine, dopamine, prostacyclin, prostaglandins and specific amino acids or neuropeptides) have been identified on microvessels and in many instances these transmitter actions are coupled to cyclic AMP synthesis. Moreover, cyclic AMP has been shown to increase the rate of capillary endothelial pinocytosis and produce brain edema. In small vessels containing smooth muscle cells cyclic AMP production improves cerebral blood flow via an initiation of vasodilatory processes. The presence of receptors for serotonin and acetylcholine have likewise been demonstrated to occur on cerebral microvessels. Limited information is available as to the receptor coupled actions of these two transmitters, but cholinergic mechanisms may act to restrict catecholamine-induced formation of cyclic AMP. Altered sensitivity of microvessels to neurotransmitters has been demonstrated following conditions of stroke, hypertension, aging, diabetes and X-irradiation.
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PMID:Neurochemical coupled actions of transmitters in the microvasculature of the brain. 287 36

Effects of S-adenosyl-L-methionine (SAMe) on experimental cerebral ischemia were investigated using two different ischemic models. Cerebral energy metabolites (ATP, lactate, c-AMP) and brain water content were measured. It is reported that SAMe accelerates synthesis of phosphatidyl choline and increases erythrocyte membrane fluidity. Complete ischemia was produced by heart excision using wistar kyoto rats. SAMe (100 mg/kg, I.P.) was administered twice at one hour and immediately before inducing ischemia. The brain of rats were irradiated by microwave to stop the enzyme activity exactly 60 seconds after inducing ischemia and brain energy metabolites were measured. Recirculation model was produced by one hour recirculation following two hours ischemia induced by clipping of bilateral common carotid arteries using stroke-prone spontaneously hypertensive rats. SAMe (100 mg/kg, I.V.) was administered twice one hour after clipping and ten minutes after recirculation. The brain metabolites and water content were measured one hour after recirculation. In the complete ischemia, ATP and c-AMP levels were statistically high in the SAMe treated group compared to the untreated group (vehicle). But there was no statistical difference in lactate between the treated group and the untreated group. In the recirculation model, lactate elevation was suppressed in the SAMe treated group compared to the vehicle group with statistical difference, but there was no difference in ATP and c-AMP. Also, there was no difference in water content between the treated and the untreated group. SAMe protected energy failure in ischemia and accelerated recovery from ischemia. It is indicated that this agent is beneficial for treatment of cerebral ischemia in the acute stage.
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PMID:[Effects of S-adenosyl-L-methionine on experimental cerebral ischemia]. 299 May 9

Glucagon has been shown to increase further the enhanced tolerance for hypoxia of mice with elevated blood ketones and to stimulate ketone utilization by rat brain slices, suggesting that glucagon may affect brain metabolism. In addition to stimulating gluconeogenesis, glucagon alters the metabolism of mitochondria isolated from liver and heart. This study was designed to test whether glucagon can act directly and selectively on brain mitochondrial substrate oxidation. Mitochondria were isolated from normal murine brains using differential centrifugation through Ficoll gradients. Glucagon (3.6 microM) stimulated respiration in the presence of glutamate, and glutamate plus beta-hydroxybutyrate, but not in the presence of glutamate plus malate, succinate or beta-hydroxybutyrate alone. With glutamate as the substrate the hormone significantly increased State 3 oxygen consumption rates from control values of 91 mol O2/mol of cytochrome aa3/min to 117 mols O2/mol/aa2/min (p less than 0.0001), and also increased State 4 rates slightly but significantly. Glucagon did not change mitochondrial respiratory control ratios, but increased estimated rates of ATP synthesis from 434 (control) to 597 mols ADP consumed/mol aa3/min (p less than 0.0001). The data indicate that in vitro glucagon has a direct and substrate-specific stimulatory effect on isolated brain mitochondria. These substrate-specific effects were not altered when respiration was studied in the presence of postmitochondrial supernatant or exogenous 3',5'-cyclic AMP, indicating that glucagon, in addition to an in vivo action via activation of membrane-bound adenylate cyclase, can act, at least in vitro, directly and selectively on brain mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke
PMID:Substrate-specific stimulation by glucagon of isolated murine brain mitochondrial oxidative phosphorylation. 300 83

The susceptibility to cerebral ischemia was studied in stroke-resistant spontaneously hypertensive rats (SHRSR) treated by a long-term antihypertensive treatment, and compared with untreated SHRSR and Wistar rats (WR). Male SHRSR, aged 8 weeks, were divided into two groups and a long-term antihypertensive treatment for 4-6 weeks was started on one group (treated SHRSR: T-SHR) while the other group was left untreated as control (untreated SHRSR: U-SHR). The changes of blood pressure were checked on these rats. The prior treatment of hypertension was achieved by administration of hydroflumethiazide (120 mg/kg/day) and captopril (15-30 mg/kg/day) orally for 4-6 weeks by mixing in drinking water. All the experiments were performed at the age of 12-16 weeks and WR of similar age served as normotensive untreated control. Cerebral ischemia was induced by bilateral common carotid artery ligation (BLCL) and blood pressure was always checked before BLCL. The survival ratio was observed from 1 hour to 24 hours after BLCL. The regional cerebral blood flow (rCBF) were measured before and 4 hours after BLCL periodically. The brain energy metabolites were measured 4 hours after BLCL. rCBF were measured at the thalamus by the hydrogen clearance method. ATP concentrations were determined by luciferine-luciferase method, c-AMP was measured by RIA and lactate by enzymatic method. The brain water content was measured by freeze-dry method.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of long-term prior antihypertensive treatment on cerebral ischemia induced by bilateral common carotid artery ligation in SHRSR]. 300 93

The Wistar rat, with a blood pressure range of 120-160 mmHg, and two strains of spontaneously hypertensive rats (SHR), stroke-prone (SHRSP, range 210-270 mmHg) and stroke-resistant (SHRSR, range 160-240 mmHg), were used to determine the degree of damage after ischemic insult induced by bilateral carotid artery ligation (BLCL). The survival rate and McGraw Stroke Index correlated well with the degree of hypertension. After BLCL, impairment of cerebral blood flow is abrupt and residual flow is near zero in rats with initial blood pressures greater than 200 mmHg. A markedly deteriorated aerobic metabolism, as measured by the concentrations of ATP, c-AMP and lactate, is seen to precipitate in rats with initial blood pressures greater than 180 mmHg and severe edema occurs if the pressure is more than 160 mmHg. The degree of hypertension that produces high vulnerability to stroke and severe damage to the brain after ischemic insult is indicated as beginning at about 180 mmHg.
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PMID:Susceptibility to ischemic insult in hypertensive rats: correlation between degree of ischemia and hypertension. 301 58


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