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

The effect exerted on the partially ischaemic heart when administering 0.9 mg/kg L-3-(beta-hydroxy-alpha-methylphenethylamino)-3'-methoxypropiophenone (oxyfedrine, ildamen) approx. 10 min after i.v. application of 0.05 mg/kg digoxin was tested on 20 dogs previously anaesthetized with propiomazine-pentobarbital. The following parameters were studied and subsequently compound with the results of former trials of ours' without digoxin premedication: aortic pressure (ASP, ADP), left-ventricular pressure (LVSP, LVEDP), heart rate (HR), cardiac output (HMV), stroke volume (SV), dp/dtmax, dp/dtmax/IP, t-dp/dtmax, blood flow in the normal and partially ischaemic myocardium, the latter being measured with heat conductance probes and labelled microspheres. ASP and ADP show the same reduction--as compared with the control value--both after the administration of oxyfedrine with and without digoxin premedication. After digoxin premedication oxyfedrine led to a somewhat less marked reduction of LVSP; on premedication with digoxin LVEDP was slightly increased whereas it was reduced after additional administration of oxyfedrine as was also the case without digoxin pretreatment. The increase in HR after oxyfedrine is almost the same as without digoxin pretreatment. Also the increase in HMV and the SV lowering are not influenced by digoxin. By administration of oxyfedrine dp/dtmax is always increased by the same amount, starting from the already increased value after digoxin premedication, which is probably an additive effect. The same applies to the quotient dp/dtmax/IP. After oxyfedrine the time t-dp/dtmax is lowered by the same amount, irrespective of a digoxin premedication. Oxyfedrine does not produce a further increase in the heat conductance values after previous application of digoxin; when measuring the blood flow with labelled microspheres the same result was found, which means that by previous administration of digoxin the circulatory effect of oxyfedrine is obviously inhibited. Summing up one can say that by combining the active principles digoxin and oxyfedrine the function parameters of the heart can be influenced only positively.
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PMID:[The action of oxyfedrine on haemodynamics, inotropism and blood perfusion of the partially ischaemic myocardium after digoxin premedication. Studies on anaesthetized dogs (author's transl)]. 719 64

Cerebral hypoxia-oligemia was produced by lowering of the arterial PO2 to 30 mm Hg and by right common carotid artery occlusion in rats who were pretreated with intravenous Krebs' solution, gamma-hydroxybutyrate (GHB) (500 mg/kg) or gamma-butyrolactone (GBL) (300 mg/kg). At 0.5 h exposure the right cerebral hemisphere of animals receiving Krebs', GHB or GBL showed equivalent decreases of ATP and phosphocreatine and increase of ADP, AMP and lactate which indicated that these depressant drugs had no beneficial effect on the energy metabolism of the acutely hypoxic-oligemic brain. In a second series of rats in which Krebs' solution, GHB or GBL were administered to animals during the early recovery period from 0.5 h hypoxic-oligemic exposure, the brain metabolic patterns of the right hemisphere indicated that GHB retarded the restitution of energy phosphates and the oxidation of the accumulated lactate; whereas, GBL led to a delayed metabolic deterioration. It is concluded that GHB and GBL do not beneficially alter cerebral energy metabolism during acute hypoxia-oligemia and that their administration during restitution may result in metabolic alterations which suggest an unfavorable effect.
Stroke
PMID:Effects of gamma-hydroxybutrate and gamma-butyrolactone on cerebral energy metabolism during exposure and recovery from hypoxemia-oligemia. 739 64

In anesthetized open chest dogs, the effects of therapeutic doses of lidocaine on myocardial cell respiration, creatine kinase depletion, left ventricular stroke work and cardiac necrosis were assessed. The dogs were subjected to 40 minutes of occlusion of the left anterior descending coronary artery, followed by 5 hours of reperfusion. Group I (12 dogs) had infusion of saline solution; group II (8 dogs) had infusion of 0.2 mg/kg per min of lidocaine (serum level 16.8 +/- 1.4 microgram/ml); group III (5 dogs) had infusion of 0.04 mg/kg per min or lidocaine (serum level 3.6 micrograms/ml). Ischemic regional myocardial blood flow (measured by 9 micrometer spheres of strontium-85) was 6.34 +/- 1.62 ml/100 mg per min in group I, 1.48 +/- 0.59 in group II (p < 0.05) and 1.32 +/- 0.50 in group III (p < 0.05). Oxygen consumed during conversion of adenosine diphosphate to adenosine triphosphate in mitochondria from control and lidocaine-treated ischemic tissue was depressed (p < 0.05) and correlated (r = 0.63) with creatine kinase depletion. Left ventricular stroke work was not significantly different among the three groups. Infarct size (in percent of left ventricular weight) was 12.6 +/- 2.0 for group I, 4.8 +/- 1.2 for group II (p < 0.01) and 4.8 +/- 2.5 for group III (p < 0.05). The data suggest that the reduction of myocardial infarct size by lidocaine was not dependent on enhanced myocardial blood flow and was independent of left ventricular stroke work.
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PMID:Lidocaine-induced reduction in size of experimental myocardial infarction. 744 28

The hemodynamic changes which occur when clamping and unclamping the aorta during reconstructive surgery might be a threat to the elderly patient with concomitant cardiac disease. In addition, the cross-clamping induces a temporary ischemia of the legs, with severe metabolic derangement after the release of the aortic clamp. We have studied the effect of a intraoperative adrenergic block (phenoxybenzamine plus metoprolol) on the central circulation and the skeletal metabolism in 14 patients undergoing aortic reconstruction to treat occlusive arteriosclerotic disease. Cardiac output, heart rate, arterial and pulmonary artery pressures, and cardiac filling pressures, as well as femoral venous blood flow were studied. Biopsy specimens of the lateral vastus muscle and blood samples from the radial artery and iliac vein were taken before aortic clamping, and before, 30 minutes, four and 16 hours after the aorta was unclamped, as well as five days postoperatively. In addition, intramuscular temperature and pH were measured. Glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and lactate and pyruvate concentrations in iliac venous and radial arterial blood were determined using enzymatic fluorometric techniques. Mean arterial blood pressure (MAP) averaged 80 mmHg before clamping, chiefly because of the low systemic vascular resistance (SVR), and left ventricular stroke work (LVSW) was normal. At clamping MAP, SVR, LVSW, remained unchanged. MAP and LVSW were unaffected even though SVR decreased slightly after the aorta was unclamped and resulted in an increased cardiac output, mainly due to a higher stroke volume. No major change in the pulmonary circulation was observed. During clamping the muscle lactate/pyruvate ratio increased, intramuscular pH and femoral venous blood flow decreased indicating insufficient tissue perfusion. Energy charge (EC), the adenylate (ATP + ADP + AMP) and creatine (PCr + Cr) pools were, however, unchanged. In spite of a restored blood flow to the legs, a severe metabolic derangement of the muscle was observed after declamping, with lowered EC, ATP + ADP + AMP and PCr + Cr indicating cellular damage. No improvement in the condition of the cells was observed 16 hours after operation. In conclusion, we found that by using neurolept anesthesia and an intraoperative adrenergic block in combination with a differentiated fluid therapy the central circulation stabilized and was largely unaffected by the clamping and unclamping procedures. In spite of the improved central hemodynamics no favorable effect on the skeletal muscle metabolism was observed.
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PMID:Temporary incomplete ischemia of the legs induced by aortic clamping in man: effects on central hemodynamics and skeletal muscle metabolism by adrenergic block. 745 55

Platelet activation plays an important role in the pathomechanisms of arterial vascular disorders including stroke, peripheral arterial disease (PAD), and myocardial infarction. Circulating activated platelets may be useful markers of local thrombotic events occurring in these diseases. Using flow cytometry circulating activated platelets can be detected by determining: 1. the platelets' shape change on the basis of the different light scatter properties of discocytes and spherocytes, 2. the expression of platelet bound fibrinogen or conformation specific neoantigens on fibrinogen and on its platelet receptor, and 3. the exposure of granule membrane proteins such as P-selectin as a result of platelet secretion. The concentration-effect relationships were determined for the ADP and U46619 induced shape change, fibrinogen binding, and expression of P-selectin. The EC50 for the shape change was 4 times lower than the EC50 for the fibrinogen binding and 29 times lower than the EC50 for the expression of P-selectin. These data clearly demonstrate that the shape change is a more sensitive indicator of platelet activation in vitro than fibrinogen binding or P-selectin expression. Both the shape change and fibrinogen binding were reversible, whereas the expression of P-selectin was irreversible upon stimulation. Reversibility of the shape change may be responsible for the fact that in patients with stroke or PAD the fraction of discocytes did not differ from controls, whereas more than 80% of them revealed a significantly higher fraction of P-selectin positive platelets. Thus the determination of the P-selectin expression reveals a higher diagnostic sensitivity for detecting a platelet activation in vivo than the determination of the shape change.
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PMID:Flow cytometric detection of activated platelets: comparison of determining shape change, fibrinogen binding, and P-selectin expression. 754 16

After 7 and 90 days of treatment, we studied the effect of picotamide, a thromboxane synthase inhibitor (450 and 900 mg/day), aspirin (150 mg/day), and aspirin plus picotamide (150 and 450 mg/day respectively) on platelet aggregation, evaluated in platelet rich plasma of 48 patients affected by ischemic stroke. Platelet aggregation, induced by collagen (1.0 and 2.0 micrograms/ml) and adenosine diphosphate (1.0 and 10 micrograms/L), was significantly increased in patients in comparison with healthy controls. Aspirin (150 mg/day) reduced collagen-induced platelet aggregation (1.0 microgram/ml) after 7 days of treatment. Picotamide (450 mg/day) reduced platelet aggregation induced by both concentrations of collagen, while the higher dose (900 mg/day) had no significant effect. Aspirin plus picotamide reduced the aggregation induced by 1.0 microgram/ml collagen and by 10 mumol/L adenosine diphosphate after 90 days of therapy. This study has shown that patients during the acute phase of stroke are characterized by an increased in vitro platelet aggregation. Aspirin may be beneficial in the acute phase of the cerebral ischemic event. Picotamide and picotamide plus aspirin could be useful for reducing platelet aggregation in long term treatment.
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PMID:Effect of picotamide and aspirin, combined or alone, on platelet aggregation in patients with cerebral infarction. 755 57

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder of unknown pathogenesis characterized by migraine and transitory hemiplegic attacks. We describe a kindred fulfilling the diagnostic criteria for FHM in which: (1) brain phosphorus magnetic resonance spectroscopy (31P-MRS) showed a reduced phosphocreatine content accompanied by high [ADP], high percentage of V/Vmax of ATP biosynthesis and decreased phosphorylation potential; (2) muscle 31P-MRS showed a reduced rate of phosphocreatine recovery after exercise; (3) blood lactate was increased after effort; (4) muscle biopsy showed, in one patient, rare ragged red fibers succinate-dehydrogenase positive and cytochrome c oxidase negative; (5) genetic analysis of muscle mitochondrial DNA did not show any of the two point mutations in the tRNA(Leu(UUR)) associated with the MELAS syndrome (Mitochondrial myopathy, Encephalopathy with Lactic Acidosis and Stroke-like episodes). The defective energy metabolism of brain and muscle found in this pedigree suggests a multisystemic disorder of mitochondrial function in this FHM pedigree.
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PMID:Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine. 760 38

The actin-myosin lattice spacing of rabbit psoas fibers was osmotically compressed with a dextran T-500, and its effect on the elementary steps of the cross-bridge cycle was investigated. Experiments were performed at the saturating Ca (pCa 4.5-4.9), 200 mM ionic strength, pH 7.0, and at 20 degrees C, and the results were analyzed by the following cross-bridge scheme: [formula: see text] where A = actin, M = myosin head, S = MgATP, D = MgADP, and P = Pi = phosphate. From MgATP and MgADP studies on exponential process (C) and (D), the association constants of cross-bridges to MgADP (K0), MgATP (K1a), the rate constants of the isomerization of the AM S state (k1b and k-1b), and the rate constants of the cross-bridge detachment step (k2 and k-2) were deduced. From Pi study on process (B), the rate constants of the cross-bridge attachment (power stroke) step (k4- and k-4) and the association constant of Pi ions to cross-bridges (K5) were deduced. From ATP hydrolysis measurement, the rate constant of ADP-isomerization (rate-limiting) step (k6) was deduced. These kinetic constants were studied as functions of dextran concentrations. Our results show that nucleotide binding, the ATP-isomerization, and the cross-bridge detachment steps are minimally affected by the compression. The rate constant of the reverse power stroke step (k-4) decreases with mild compression (0-6.3% dextran), presumably because of the stabilization of the attached cross-bridges in the AM*DP state. The rate constant of the power stroke step (k4) does not change with mild compression, but it decreases with higher compression (> 6.3% dextran), presumably because of an increased difficulty in performing the power stroke. These results are consistent with the observation that isometric tension increases with a low level of compression and decreases with a high level of compression. Our results also show that the association constant K5 of Pi with cross-bridge state AM*D is not changed with compression. Our result further show that the ATP hydrolysis rate decreased with compression, and that the rate constants of the ADP-isomerization step (k6) becomes progressively less with compression. The effect of compression on the power stroke step and rate-limiting step implies that a large-scale molecular rearrangement in the myosin head takes place in these two slow reaction steps.
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PMID:The effect of the lattice spacing change on cross-bridge kinetics in chemically skinned rabbit psoas muscle fibers. II. Elementary steps affected by the spacing change. 767 97

The ATP-sensitive potassium channels (KATP) are activated either by a decrease in intracellular ATP content or by a lowering of the ATP-ADP ratio such as during stroke. We studied the role of cerebral KATP on arterial pressure during acute reduction of cerebral blood flow in 12-week-old male Wistar rats anesthetized with urethane by recording arterial pressure and heart rate continuously. After bilateral ligation of the common carotid arteries, glibenclamide, a specific blocker of KATP, was injected intracerebroventricularly into the cerebral lateral ventricle. Glibenclamide elicited a sustained vasopressor response in a dose-dependent manner in rats with bilateral carotid artery ligation (10 nmol, +15 +/- 2 mm Hg; 1 nmol, +5 +/- 1 mm Hg, P < .01 versus vehicle), but hemodynamic alterations were barely recorded with glibenclamide in sham-operated control rats. The abdominal sympathetic discharge was not increased significantly enough to explain the pressor mechanism. Similarly, pretreatments with intravenous injections of bunazosin, an alpha 1-adrenoceptor antagonist, did not affect the pressor response of intracerebroventricular glibenclamide. To investigate the vasopressor mechanism further, we measured plasma and pituitary concentrations of arginine vasopressin and determined the effects of vasopressin receptor antagonists. The intracerebroventricular injections of glibenclamide significantly increased the plasma concentration of vasopressin (P < .05) and significantly decreased the pituitary concentration of vasopressin (P < .05) in rats with bilateral carotid artery ligation. Intravenous pretreatment with the vasopressin V1 receptor antagonist OPC-21268 abolished the vasopressor response to intracerebroventricular glibenclamide (+16 +/- 2 versus +1 +/- 1 mm Hg, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral ATP-sensitive potassium channels during acute reduction of carotid blood flow. 773 18

Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PBN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PBN was given 1 hr after recirculation. Neocortical focal and perifocal ("penumbra") areas were sampled for analyses of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion of glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PBN on mitochondria cannot be excluded, the results suggest that PBN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.
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PMID:N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia. 776 48


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