Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The double subarachnoid hemorrhage canine model was used to test the prophylactic value of immunosuppression in the prevention of cerebral vasospasm after subarachnoid hemorrhage. Dogs treated with cyclosporine A following the regimen prescribed for organ transplant procedures in patients showed a significant reduction in the severity of angiographic constriction of cerebral arteries. While basilar artery diameter after double experimental subarachnoid hemorrhage in a series of untreated dogs (n = 34) averaged 65% of baseline diameter, arterial diameter in dogs treated prophylactically (n = 18) with 6 mg/kg/day cyclosporine A and adjunct low-dose steroid averaged 80% of baseline diameter, for a mean reduction in the severity of chronic arterial constriction of 42%. More important than the average effect, however, is the statistical observation that this mean improvement was obtained primarily by a dramatic reduction in the incidence of severe cerebral vasospasm, the situation most likely to account for morbidity and mortality after aneurysmal rupture.
Stroke 1990 Jan
PMID:Cyclosporine A reduces cerebral vasospasm after subarachnoid hemorrhage in dogs. 202 83

We used laser-Doppler flowmetry to study the effects of endothelin-1 on local cortical microvascular perfusion and resistance in 29 pentobarbital-anesthetized rats. Intravenous administration of 10-300 pmol endothelin-1 reduced arterial blood pressure and microvascular resistance and increased microvascular perfusion. However, intracarotid administration of low doses of endothelin-1 increased microvascular perfusion and reduced microvascular resistance and arterial blood pressure, whereas high doses (greater than or equal to 300 pmol) reduced microvascular perfusion and increased microvascular resistance and arterial blood pressure. Only the high dose/low flow response was associated with attenuation of the electrocorticogram. The low dose/high flow and high dose/low flow responses to endothelin-1 were not altered by blockade of muscarinic and adrenergic receptors. In addition, systemic metabolic changes (arterial pH, PaCO2, PaO2, and plasma glucose concentration) did not account for the cerebrovascular effects of endothelin-1. Platelet hyperaggregability also did not appear to be a causative factor in the high dose/low flow response to endothelin-1. In fact, ex vivo rat platelet aggregation was inhibited by intracarotid administration of 300 pmol endothelin-1. In conclusion, the cerebral vasculature exhibits extreme sensitivity to the vasodilator properties of endothelin-1 at low doses. The ischemic vasoconstrictor effects observed at high doses implicate endothelin-1 as an important mediator of cerebral vasospasm and/or postischemic hypoperfusion.
Stroke 1990 Mar
PMID:Effect of endothelin on cortical microvascular perfusion in rats. 240 98

Intravascular volume expansion has been employed successfully for treatment of ischemic stroke from cerebral vasospasm and from cerebrovascular occlusive disease. The physiologic mechanism responsible for this success has not previously been delineated in controlled experimentation. The objective of this investigation was to delineate the effects of cardiac output and of hemodilution in a primate model of focal cerebral ischemia. Two groups of anesthetized rhesus monkeys received extensive cardiovascular monitoring, and local cerebral blood flow (lCBF) was determined in both ischemic and nonischemic brain regions by the hydrogen clearance method. Both groups were subjected to unilateral middle cerebral artery occlusion. One group then underwent blood volume expansion with Dextran 40 (cardiac output augmentation), and one group underwent isovolemic hemodilution with Dextran 40, cardiac output being maintained constant. Significant increases in lCBF occurred in ischemic regions only and occurred only in response to augmentation of cardiac output. Isovolemic hemodilution failed to produce any changes in lCBF. This investigation indicates that ischemic brain regions are selectively vulnerable to alterations in cardiac output, these effects being independent of alterations in blood pressure. Blood viscosity changes may play only a minor role. This study strongly suggests an important role of intravascular volume expansion and cardiac output augmentation in treatment of acute ischemic stroke.
 ...
PMID:Modification of focal cerebral ischemia by cardiac output augmentation. 241 67

Blood proteins could play a critical role in the pathogenesis of cerebral vasospasm in subarachnoid hemorrhage (SAH) as agonists and as antagonists of vasoconstriction. The present study was designed primarily to quantify the inhibition produced by antithrombin III of the phasic responses elicited by cumulative doses of KCl, serotonin (5-HT), uridine triphosphate (UTP), and thrombin in isolated canine basilar arteries, and to ascertain whether other proteins might act similarly. Antithrombin III (1 unit/ml and 3 units/ml) given 2 min beforehand inhibited all agonists. The inhibition was not dependent on a functional endothelium nor due to stimulation of the electrogenic sodium pump. Alpha2-macroglobulin (0.1 mg/ml and 0.4 mg/ml) inhibited the contractile responses to high K+, 5-HT and thrombin. Kallikrein (1 and 4 units/ml) did not inhibit UTP but inhibited high K+ and 5-HT through an effect on the endothelium. Kallikrein (1 unit/ml) irreversibly blocked the responses to thrombin. Globulins (3 mg/ml) and fibrinogen (0.3 mg/ml) were not inhibitory. The results demonstrate that anticoagulant proteins are very effective nonspecific inhibitors of the vasoconstriction, whereas the serine protease kallikrein selectively blocks thrombin. The remarkable potency of antithrombin III suggests that it may protect cerebral arteries from exhibiting vasospasm in SAH.
Stroke
PMID:Vasodilator proteins: role in delayed cerebral vasospasm. 242 60

We compared responses to calcium ionophore A23187, vasopressin, and substance P in helical strips of dog middle cerebral, basilar, and posterior communicating arteries to obtain a better understanding of humoral control of cerebrovascular tone in different brain regions and its potential impact on mechanisms of cerebral vasospasm. A23187 relaxed these different arterial strips partially precontracted with prostaglandin F2 alpha to a similar extent. Vasopressin produced concentration-dependent relaxation in basilar and posterior communicating arterial strips, whereas middle cerebral arterial strips either contracted or relaxed slightly. Relaxations induced by A23187 and vasopressin were either abolished or converted to contractions by removal of the endothelium. In contrast, the relaxation of cerebral arterial strips to substance P was markedly attenuated but not abolished by endothelium denudation; the remaining relaxation was suppressed by indomethacin. In some cerebral arterial strips with intact endothelium, substance P caused a transient contraction that was reversed to a relaxation by indomethacin or ONO-3708, a prostaglandin antagonist. In arterial strips denuded of endothelium from the same dogs, substance P always produced relaxations. Relaxations of cerebral arterial strips to A23187 and vasopressin appear to be mediated by endothelium-derived relaxing factor. The function of vasopressin receptors in endothelial cells differs markedly in basilar and posterior communicating arteries versus middle cerebral arteries. Substance P-induced relaxations appear to be primarily associated with endothelium-derived relaxing factor and with prostaglandin I2, whereas contractions appear to be mediated by endothelium-derived prostaglandins.
Stroke 1988 Nov
PMID:Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries. 246 Sep 77

We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KCl (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. Endothelium-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endothelium and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I2, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KCl, serotonin, and prostaglandin F2 alpha were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.
Stroke 1989 May
PMID:Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances. 247 Jan 67

We investigated the possible relation between neuropeptides and cerebral vasoconstriction in samples of ventricular or cisternal cerebrospinal fluid from 14 patients with subarachnoid hemorrhage. Neuropeptide Y, calcitonin gene-related peptide, atrial natriuretic peptide, and pituitary polypeptide 7B2 were present in the cerebrospinal fluid of these patients. Concentrations of calcitonin gene-related peptide and 7B2 were not significantly different from those in control subjects, but that of atrial natriuretic peptide was significantly lower. Although the mean concentration of neuropeptide Y was not significantly higher than control, consecutive determinations showed an increase 6-11 days after the onset of subarachnoid hemorrhage. An initially high 7B2 concentration decreased gradually, although half the patients showed a second increase greater than 10 days after the onset. Considering the well-recognized vasoconstrictive effect of neuropeptide Y, it is possible that this increase in its concentration in the cerebrospinal fluid plays a role in the pathogenesis of the cerebral vasospasm that is often seen after subarachnoid hemorrhage.
Stroke 1989 Dec
PMID:Increased neuropeptide Y concentrations in cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage. 253 45

Nimodipine is a dihydropyridine calcium antagonist which has been shown to dilate cerebral arterioles and increase cerebral blood flow in animals and humans. It has potential in the treatment of a range of cerebrovascular disorders. Major interest to date, however, has focused on its use in the prevention and treatment of the delayed ischaemic neurological deficits that frequently occur in patients with subarachnoid haemorrhages as a result of sustained cerebral vasospasm. Initial studies in which patients were treated with an intravenous infusion of nimodipine for up to 2 weeks, followed by oral treatment for 7 days, indicated that a higher proportion of patients than would normally be expected recovered with little or no permanent neurological damage. In a number of controlled studies oral nimodipine treatment for 3 weeks significantly decreased mortality rates and increased the number of patients who had a 'good' neurological outcome as compared with placebo treatment. In some of these trials fewer of the nimodipine-treated patients developed neurological deficits during the treatment period, but in none was there a significant effect on the incidence of angiographic vasospasm. It would seem that other pharmacological actions, such as increasing collateral blood flow to underperfused regions or a direct anti-ischaemic effect at the cellular level, may contribute to the clinical benefits obtained with nimodipine treatment. Preliminary results suggest that nimodipine is potentially useful in other cerebrovascular disorders, particularly ischaemic stroke. To date, nimodipine has been well-tolerated, the only adverse effects of any significance being reductions in the blood pressure of some patients and reversible increases in liver enzymes during intravenous therapy. Thus, nimodipine has significant potential in the treatment of patients with subarachnoid haemorrhage. Wider clinical use should confirm its value as a significant addition to the very limited range of therapeutic choices currently available for patients with this disorder.
 ...
PMID:Nimodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cerebrovascular disease. 266 15

Recent evidence supports the concept that cerebral vasospasm is involved in the pathogenesis of eclampsia. Magnesium, which has a beneficial effect in eclampsia, may act by opposing calcium-dependent arterial constriction, thereby relieving vasospasm. Magnesium may also antagonize the increase in intracellular calcium concentration caused by ischemia and thus prevent cell damage and death. Magnesium might have a role in the treatment of cerebral vasospasm and ischemia, such as occurs in subarachnoid hemorrhage, ischemic stroke, and brain trauma.
Stroke 1989 Sep
PMID:Action of magnesium sulfate in the treatment of preeclampsia-eclampsia. 267 28

We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73 +/- 4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. Our observations suggest that endothelin acts in cerebral vessels from the adventitial side, not from the luminal side, possibly due to the presence of the blood-arterial wall barrier. The long-lasting nature of endothelin-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.
Stroke 1989 Nov
PMID:Endothelin acts in feline and canine cerebral arteries from the adventitial side. 268 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>