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

Since adenosine may play a role in the hyperdynamic circulation of cirrhosis, we examined the effects of theophylline (an adenosine receptor antagonist) on systemic and splanchnic hemodynamics, tissue oxygenation and sympathoadrenal activity in patients with cirrhosis and liver failure. Theophylline (aminophylline) was administered intravenously for 30 min. Six patients received a dose of 3 mg/kg and eight others a dose of 6 mg/kg. The low dose caused plasma theophylline concentrations of 7.4 +/- 1.8 mg/ml (mean +/- S.E.), and induced a significant increase in heart rate from 84 +/- 5 to 93 +/- 8 beats/min. This dosage did not significantly change other hemodynamic values, oxygen (O2) consumption, or sympathoadrenal activity. The high dose elicited plasma theophylline concentrations of 15.8 +/- 4.0 mg/ml. This dose significantly increased heart rate from 78 +/- 5 to 87 +/- 7 beats/min and significantly decreased right atrial pressure from 2.5 +/- 1.0 to 1.4 +/- 0.8 mmHg, stroke volume from 52 +/- 3 to 47 +/- 5 ml.beat-1.m-2 and systolic arterial pressure from 140 +/- 5 to 129 +/- 6 mmHg. In contrast, O2 consumption, sympathoadrenal activity, and all other hemodynamic values (including azygos blood flow) were not significantly modified. As a result, we conclude that, in patients with cirrhosis, theophylline may cause decreased stroke volume which lowers systolic arterial pressure. In our patients theophylline also had a positive chronotropic effect but no vasoconstrictor effect on systemic and splanchnic circulation. Finally, theophylline did not improve tissue oxygenation in patients with cirrhosis.
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PMID:Effects of theophylline on hemodynamics and tissue oxygenation in patients with cirrhosis. 144 98

Adenosine has been proposed as a metabolic factor involved in the regulation of cerebral blood flow. The evidence in support of this hypothesis, presented in this review, includes information on the adenosine receptors associated with cerebral blood vessels, the synthesis and metabolism of adenosine, and the release of adenosine from the brain. Adenosine dilates cerebral blood vessels, acting at an A2 receptor. The critical evidence implicating an involvement of adenosine in cerebrovascular regulation is derived from experiments with adenosine antagonists and potentiators. The antagonists include methylxanthine adenosine receptor antagonists and the enzyme adenosine deaminase. Potentiators include transport inhibitors, enzyme inhibitors, and adenosine precursors. Adenosine has been implicated in vascular regulation during hypoxia/ischemia, hypercapnia, seizures, severe hypotension, and hypoglycemia. Adenosine possesses a number of properties that can be used to minimize neuronal degeneration during cerebral insults, such as ischemia, including vasodilatation, reduction of excitatory transmitter release, reduction of membrane calcium permeability, inhibition of platelets, and neutrophil aggregation. Several recent studies have demonstrated that manipulation of central adenosine tone can alter the extent of cerebral ischemic damage, indicating a potential new therapeutic approach for the treatment of stroke.
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PMID:Adenosine in the control of the cerebral circulation. 270 69

We investigated the effect of adenosine on neurogenic contraction of the canine cavernous carotid artery, using an isometric tension recording device and transmural nerve stimulation. Adenosine, in concentrations under 10(-5)M, had no relaxing effect on the contractions produced by high [K]o solution or 10(-5)M norepinephrine. Transmural nerve stimulation (stimulus: 1 msec duration, 100V intensity) evoked a frequency-dependent contraction, which was abolished by 3 X 10(-7)M tetrodotoxin. Adenosine in concentrations of 10(-6)M and 10(-5)M, inhibited the neurogenic contraction at each frequency, more so in the low frequency range. This inhibitory effect of adenosine was significantly antagonized by 10(-5)M theophylline. Pretreatment with 2 X 10(-8)M dipyridamole had no effect on neurogenic contractions, but augmented the inhibitory effect of adenosine. 10(-5)M theophylline did not augment the neurogenic contractions. The findings that both dipyridamole and theophylline failed to affect the neurogenic contractions in the absence of adenosine suggests that the presynaptic autoinhibition mechanism of adenosine may not be involved in neuromuscular transmission in this tissue. These results suggest that there is a presynaptic adenosine receptor in the nerve terminal which inhibits the release of neurotransmitter in canine cavernous carotid artery. It is also probable that the vasodilating effect of adenosine in the cavernous carotid artery is mainly due to its inhibitory effect on neurotransmission rather than to a direct relaxing effect on smooth muscle.
Stroke
PMID:Presynaptic inhibitory action of adenosine on neuromuscular transmission in the canine cavernous carotid artery. 300 84

Sixty-five male gerbils were exposed to 30 minutes of cerebral ischemia induced by a bilateral carotid artery occlusion. One group of 15 gerbils received a single injection of 25 microliter of 5 microM cyclohexyladenosine into the cerebral ventricle 15 minutes after release of the occlusion. Another group of 45 gerbils received a similar injection of the vehicle. Five days after ischemia, the hippocampal histology was examined under light microscopy. In the gerbils treated with the adenosine receptor agonist N-6-cyclohexyladenosine, the CA1 region of the hippocampus showed significant quantitative pyramidal cell preservation (p less than 0.01, Mann-Whitney U test). Qualitatively, substantial destruction of CA1 neurons was present in all hippocampi of the vehicle-injected gerbils. The CA1 neurons in the cyclohexyladenosine-treated gerbils did not differ from those seen in the five nonischemic controls. The precise mechanism of the protective action of cyclohexyladenosine is unknown, although it has been demonstrated that adenosine agonists reduce presynaptic glutamate release in vitro. It is possible that postischemic administration of cyclohexyladenosine decreases the release of this neurotransmitter in the intact brain as well. The concomitant reduction of the neurotoxic effect of glutamate may, therefore, result in better histologic preservation of the pyramidal cells in the postischemic CA1.
Stroke 1988 Sep
PMID:Cyclohexyl adenosine protects against neuronal death following ischemia in the CA1 region of gerbil hippocampus. 341 11

Adenosine receptors have been identified on brain cortical membranes and microvascular preparations. However, they have not been demonstrated on specific microvascular elements in isolation. 2-3H-chloroadenosine was used as a ligand to investigate the presence of adenosine receptors on isolated mouse cerebral smooth muscle membranes. The binding studies reveal the presence of a high affinity binding site with a Kd value of 33.3 nM and a maximal binding capacity (Bmax) of 283 fmol/mg protein. These findings demonstrate that there is an adenosine receptor on cerebral smooth muscle membranes.
Stroke
PMID:Demonstration of adenosine receptors on mouse cerebral smooth muscle membranes. 608 2

1. The purpose of the present study was to develop an experimental strategy for the quantification of the cardiovascular effects of non-selective adenosine receptor ligands at the adenosine A1 and A2a receptor in vivo. 2-Chloroadenosine (CADO) was used as a model compound. 2. Three groups of normotensive conscious rats received an short intravenous infusion of 1.4 mg kg-1 CADO during constant infusions of the A1-selective antagonist, 8-cyclopentyltheophylline (CPT; 20 micrograms min-1 kg-1), the A2a-selective antagonist, 8-(3-chlorostyryl) caffeine (CSC; 32 micrograms min-1 kg-1) or the vehicle. The heart rate (HR) and mean arterial blood pressure (MAP) were recorded continuously during the experiment and serial arterial blood samples were taken for analysis of drug concentrations. The ratio MAP/HR was also calculated, which may reflect changes in total peripheral resistance on the assumption that no changes in stroke volume occur. 3. During the infusion of CPT, CADO produced a reduction in both blood pressure and MAP/HR by activation of the A2a receptor. The concentration-effect relationships were described according to the sigmoidal Emax model, yielding potencies based on free drug concentrations (EC50,u) of 61 and 68 ng ml-1 (202 and 225 nM) for the reduction of blood pressure and MAP/HR, respectively. During the infusion of CSC, an EC50,u value of 41 ng ml-1 (136 nM) was observed for the A1 receptor-mediated reduction in heart rate. The in vivo potencies correlated with reported receptor affinities (Ki(A1) = 300 nM and Ki(A2a) = 80 nM). The maximal reductions in MAP/HR and heart rate were comparable to those of full agonists, with the Emax values of -12 +/- 1 x 10(-2) mmHg b.p.m.-1 and -205 b.p.m. respectively. 4. It is concluded that this integrated pharmacokinetic-pharmacodynamic approach can be used to obtain quantitative information on the potency and intrinsic activity of new non-selective adenosine receptor agonists at different receptor subtypes in vivo.
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PMID:Pharmacokinetic-haemodynamic relationships of 2-chloroadenosine at adenosine A1 and A2a receptors in vivo. 873 40

The cardiovascular effects of the nonselective adenosine receptor agonist 8-butylaminoadenosine (BAA) were quantified in conscious normotensive rats. The potency and intrinsic activity for the A1 and A2a receptor were determined separately. The rats received a short intravenous infusion of 100 mg/kg BAA in combination with a continuous infusion of either the A1-selective antagonist 8-cyclopentyltheophylline (CPT) (8 micrograms/min/kg), the A2a-selective antagonist 8-(3-chlorostyryl)caffeine (CSC) (32 micrograms/min/kg) or the vehicle. Heart rate (HR) and mean arterial pressure (MAP) were recorded continuously as pharmacodynamic indices for adenosine receptor activation. The MAP/HR ratio was derived as an additional cardiovascular parameter. This ratio reflects changes in total peripheral resistance on the assumption that stroke volume remains constant. During the infusion of CSC, the potency and intrinsic activity for the A1 receptor were estimated by relating the negative chronotropic effect to BAA blood concentrations. The sigmoidal curve yielded a potency value based on unbound concentrations (EC50,u) of 1.9 +/- 0.4 micrograms/ml (mean +/- S.E.; n = 5). The maximal reduction (Emax) in HR (-85 +/- 9 beats/min) was significantly smaller than the values reported for full agonists. During A1 blockade, EC50,u values of 5.5 +/- 0.8 and 6.0 +/- 0.8 micrograms/ml were observed for the A2a receptor-mediated reductions in blood pressure and MAP/HR, respectively (mean +/- SE; n = 5). The Emax values for the hypotensive effect and the reduction in MAP/HR (-55 +/- 3 beats/min and -9.7 +/- 0.6 x 10(-2) mm Hg/ beats/min, respectively) were similar to those of a full A2a receptor agonist. This study shows that BAA is a partial agonist for the adenosine A1 receptor and a full agonist for the A2a receptor.
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PMID:Partial agonism of the nonselective adenosine receptor agonist 8-butylaminoadenosine at the A1 receptor in vivo. 896 69

Despite significant progress in understanding of the potential of adenosine A1 receptor-based therapies in treatment of cerebral ischemia and stroke, very little is known about the effect of selective stimulation of adenosine A2A receptors on the outcome of a cerebrovascular arrest. In view of a major role played by adenosine A2 receptors in the regulation of cerebral blood flow, we have investigated the effect of both acute and chronic administration of the selective adenosine receptor agonist 2-[(2-aminoethylamino)-carbonylethylphenylethylamino]-5'-N- ethylcarboxoamidoadenosine (APEC) and antagonist 8-(3-chlorostyryl)caffeine (CSC) on the outcome of 10 min ischemia in gerbils. Acute treatment with APEC improved recovery of postischemic blood flow and survival without affecting neuronal preservation in the hippocampus. Acute treatment with CSC had no effect on the cerebral blood flow but resulted in a very significant protection of hippocampal neurons. Significant improvement of survival was present during the initial 10 days postischemia. Due to subsequent deaths of animals treated acutely with CSC, the end-point mortality (14 days postischemia) in this group did not differ statistically from that seen in the controls. It is, however, possible that the late mortality in the acute CSC group was caused by the systemic effects of brain ischemia that are not subject to the treatment with this drug. Chronic treatment with APEC resulted in a statistically significant improvement in all studied measures. Although chronic treatment with CSC improved postischemic blood flow, its effect on neuronal preservation was minimal and statistically insignificant. Mortality remained unaffected. The results indicate that the acute treatment with adenosine A2A receptor antagonists may have a limited value in treatment of global ischemia. However, since administered CSC has no effect on the reestablishment of postischemic blood flow, treatment of stroke with adenosine A2A receptor antagonists may not be advisable. Additional studies are necessary to elucidate whether chronically administered drugs acting at adenosine A2 receptors may be useful in treatment of stroke and other neurodegenerative disorders.
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PMID:Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. 899 4

The inhibitory neuromodulator adenosine is neuroprotective against damage induced by cerebral ischemia. Its vasodilator effects add to its suitability as a possible anti-stroke agent, but also account for unwanted side effects following systemic administration of adenosine receptor agonists. ATP breakdown during ischemia produces adenosine which effluxes out of the neuron. This review will focus on endogenously produced adenosine and its subsequent protection against ischemia-induced neuronal damage in some stroke models, but will also highlight possible disadvantages to increasing adenosine concentrations. In the advantages column, therapeutic benefits have been obtained by enhancing synaptic concentrations of endogenous adenosine using the adenosine uptake inhibitor propentofylline, but not dipyridamole. There is an emerging role for endogenous adenosine in preventing delayed cell death, e.g. following hypoxic pre-conditioning. One of the cons associated with enhancing the synaptic concentration of adenosine is the appearance of adenosine receptor desensitization over time. Thus, there is a therapeutic window of opportunity during which activation of an adenosine A1 receptor is beneficial to an ischemic neuron.
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PMID:Neuroprotective effects of adenosine in cerebral ischemia: window of opportunity. 906 44

Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A(1) adenosine receptor. However, the role played by the A(2A) receptor has been obscured by intrinsic limitations of A(2A) adenosinergic agents. To overcome these pharmacological limitations, we explored the consequences of deleting the A(2A) adenosine receptor on brain damage after transient focal ischemia. Cerebral morphology, as well as vascular and physiological measures (before, during, and after ischemia) did not differ between A(2A) receptor knock-out and wild-type littermates. The volume of cerebral infarction, as well as the associated neurological deficit induced by transient filament occlusion of the middle cerebral artery, were significantly attenuated in A(2A) receptor knock-out mice. This neuroprotective phenotype of A(2A) receptor-deficient mice was observed in different genetic backgrounds, confirming A(2A) receptor disruption as its cause. Together with complimentary pharmacological studies, these data suggest that A(2A) receptors play a prominent role in the development of ischemic injury within brain and demonstrate the potential for anatomical and functional neuroprotection against stroke by A(2A) receptor antagonists.
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PMID:A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice. 1053 22


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