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

The pathophysiology of xenograft hyperacute rejection is still poorly understood although it is believed to involve complement fixation to vascular endothelium, probably as a result of the presence of naturally occurring anti-species antibodies. Hyperacute rejection of pig hearts by human blood was studied in an ex-vivo working heart model. Cardiac performance and immunological reactions occurring in the perfusing blood were studied. Stroke work performed by pig hearts perfused with human blood and their survival (median 47 min: n = 10) was significantly reduced compared to survival (median 158 min: n = 10) and stroke work performed by pig hearts perfused with pig blood. Decomplementation of human blood resulted in improved performance and duration of the action (median survival > 240 min: n = 10) of hearts. Quantitative differences were seen in complement fixation between the groups. Our data demonstrate the central role of complement in the destruction of pig-to-man xenografts.
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PMID:A comparison of the performance of pig hearts perfused with pig or human blood using an ex-vivo working heart model. 803 64

Despite important new diagnostic laboratory and imaging technologies, the cause of brain infarction remains unexplained in 20% to 40% of subjects. Most stroke patients do not require extensive evaluations of coagulation, but hypercoagulability may account for a significant proportion of unexplained strokes. Hemostatic abnormalities associated with stroke may be broadly classified as familial or acquired. Principal among the familial thrombotic coagulopathies are deficiencies in concentration or function in protein-C, protein-S, and antithrombin III, but other hereditary abnormalities include sickle cell disease, homocystinuria, and dysfibrinogenemia. The acquired disorders of hemostasis associated with stroke probably constitute a larger proportion of the important stroke-related coagulopathies. In particular, the aPL antibody syndrome is now strongly associated with thrombotic events including stroke, although neither the mechanism of thrombosis nor effective therapies for this syndrome have been clearly elucidated. Many of the acquired hemostatic abnormalities exist within a special clinical setting such as with malignancy or with myeloproliferative diseases, nephrotic syndrome, and liver disease. Presumably many of these share common pathways of coagulation activation or dysfunction with the inherited disorders. Most of the hemostatic disorders in stroke are associated with dysfunction of vascular endothelium and abnormalities of or interference with the natural anticoagulant proteins: protein-C, protein-S, and antithrombin III. Improved understanding of these relationships should lead to better diagnosis and treatment for people at risk of stroke.
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PMID:Abnormalities of hemostasis in ischemic stroke. 841 25

The prevalence of hypertension in diabetes is significantly higher than in non-diabetics, perhaps twice as common. The excess is related to diabetic nephropathy, mainly in type 1 diabetes, to obesity, mainly in type 2 diabetes, but also to increased sympathetic activity. Furthermore, the increased prevalence of hypertension may relate to insulin resistance and its sequelae. Insulin resistance leads to hyperinsulinemia, relates to increased LDL and reduced HDL levels, causes the development of impaired glucose tolerance and type 2 diabetes and might also be causally related to the onset of hypertension. Syndrome X has relevant therapeutic implications in the management of hypertension. Hypertension is a major risk factor for large vessel disease in diabetics and also a risk factor for microangiopathy, particularly nephropathy. The incidence of atherosclerotic disease is dramatically increased in both type 1 and type 2 diabetics and is the major cause of morbidity and premature death mainly in patients with raised urinary albumin excretion. Thus, diabetics show a two-fold increased risk of coronary heart disease, 2-6 fold increased risk of stroke and a several-fold increased risk of peripheral vessel disease. Some evidence suggests that hypertension may be a risk factor for retinopathy, particularly its progression, but surely hypertension is a significant risk factor for nephropathy, accelerating its progression and perhaps even causing the onset of the glomerulopathy. The mechanisms by which hypertension might contribute to the evolution of both large vessel as well as small vessel disease is still unknown, although increased capillary leakage and vascular endothelium alterations might be important factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hypertension and diabetes]. 856 58

In situ hybridization to mitochondrial ribosomal RNA (rRNA) has been used to study the distribution of mitochondria in paraffin-embedded autopsy brain tissue from two patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and other organs from one of the patients. Comparison of in situ hybridization and electron microscopic findings in an antemortem biopsy specimen of pylorus from the latter patient showed a close correspondence between the distribution of hybridization signal on light microscopy and of mitochondria in ultrathin sections. Strong hybridization signal was present over smooth muscle fibres of the muscularis externa, which contained abnormal accumulations of mitochondria on electron microscopy. Hybridization to sections of skeletal muscle confirmed previous reports of 'ragged-red' fibres in this disorder and of mitochondrial accumulations in the walls of intramuscular blood vessels. To try to elucidate the role of vessel wall accumulation of mitochondria in the genesis of the stroke-like lesions, the distribution of mitochondrial rRNA was assessed in sections of brain from both of the cases of MFLAS and several cases of atherothrombotic cerebrovascular disease. Blood vessels in and adjacent to the cerebral lesions of MELAS showed strong hybridization signal with the mitochondrial probes, as was also seen in infarcts of various ages in the control brains. Only weak signal was present in the walls of blood vessels distant from the lesions, in both MELAS and control brains. These findings suggest that mitochondria accumulate in vascular endothelium and tunica media as a normal response to cerebral infarction or ischaemia. The accumulation of mitochondria in the cerebral lesions of MELAS may, at least in part, be a reaction to the destructive effects of the underlying metabolic dysfunction.
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PMID:Assessment of the distribution of mitochondrial ribosomal RNA in melas and in thrombotic cerebral infarcts by in situ hybridization. 868 87

The fibrinolytic activity status of the patients with cerebral infarction can affect their clinical prognosis. In this case-controlled study, the plasma fibrinolytic system activities in 30 cases of cortical artery territory cerebral infarction (CACI) and 32 cases of perforating artery territory cerebral infarction (PACI) with a disease duration less than 3 days were assayed with a comprehensive panel including the plasma tPA activity, PAI activity, tPA releasing capacity from vascular endothelium and PAI/tPA ratio values. 30 subjects without cardiovascular and cerebrovascular disorders were served as control. The results showed that the plasma fibrinolytic system activities of the patients with aforementioned two subtypes of cerebral infarction were significantly lower than those of the controls, the results provide a theoretical basis for carrying out thrombolytic therapy in patients with ischemic stroke and suggest that recurrent cerebral infarction might be related to the high activity of plasma PAI.
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PMID:[An analysis on the activity status of fibrinolytic system in Chinese patients with acute cerebral infarction]. 869 8

Hyperhomocyst(e)mia (Hcy) negatively influences vascular endothelium and coagulation factors. Association of Hcy with premature arteriosclerosis (rather than atherosclerosis), stroke, myocardial infarction and peripheral arterial and venous disease was proved in clinical and epidemiological studies, even as the association with conventional risk factors like age, male sex, smoking, hypertension and hypercholesterolemia. Vitamin substitution of folates, vitamin B6 and B12 decreases Hcy blood levels, however definite evidence is still lacking, whether it results in lower incidence and mortality from cardiovascular diseases. Therefore clinical and epidemiological studies are necessary. Before the grant-application we proved in a pilot study significantly higher Hcy levels in 97 patients with manifest ischaemic heart disease than in 37 controls.
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PMID:[Homocysteine, a less well-known risk factor in cardiac and vascular diseases]. 870 81

Treatment of hypertension has reduced the incidence of stroke, heart failure and renal failure. However, the incidence of coronary heart disease is not reduced to the same degree. Many of the drugs advocated as first-line drugs in the step-wise therapy have been shown to cause carbohydrate intolerance and it is an independent risk factor in the development of coronary heart disease. It is thus important to identify the antihypertensive drugs that may cause deterioration in glucose tolerance. Cicletanine, the first derivative of the furopyridines, is a new class of antihypertensive agents. It acts directly on vascular endothelium cells by increasing prostacyclin synthesis. It also decreases intracytosolic calcium levels in smooth muscles. The purpose of this study is to evaluate the effects of Cicletanine on insulin release in rat isolated pancreas by the perfusion technique adapted from Loubatieres and co-workers (1972). Doses used were based on therapeutic peak plasma concentration. Diazoxide was used as a positive control ie a known insulin suppressant. Cicletanine at 1/10 and equivalent therapeutic concentrations (0.5 microgram/mL and 5.0 micrograms/mL) did not suppress insulin release. However, at concentration exceeding 10X its therapeutic levels (50 micrograms/mL) it begins to suppress insulin release. In conclusion, Cicletanine did not inhibit insulin release at concentrations within the therapeutic range.
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PMID:The effects of Cicletanine, a new antihypertensive agent on insulin release in rat isolated pancreas by the perfusion technique. 894 29

Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent vasoactive agents, including the vasodilator molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET)-1. A dysfunction of the vascular endothelium has been implicated in the pathophysiology of a number of cardiovascular diseases, important among which is essential hypertension. Impairment of NO synthesis, or increased inactivation of NO by superoxide radicals, may account for the increased peripheral vascular tone associated with hypertension, as well as contribute to the clinical consequences of this condition, which include vascular hypertrophy, increased platelet and monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and stroke. Similarly, increased ET-1 synthesis, or increased smooth muscle sensitivity to ET-1, could account for many of the features of hypertension, including increased peripheral vascular tone and vascular hypertrophy. Modulation of endothelial function is, therefore, an attractive therapeutic option in the treatment of hypertension. Calcium antagonists have been shown to enhance the effects of NO, and inhibit those of ET-1, on vascular smooth muscle cells. In addition, calcium antagonists have antiatherogenic and antioxidant properties and could, therefore, prove to be useful therapeutic agents in preventing some of the important complications of hypertension. The long term effects on cardiovascular morbidity and mortality of the long-acting nifedipine gastrointestinal therapeutic system (nifedipine GITS) used in the treatment of essential hypertension are currently being investigated in the first multinational outcome study (INSIGHT) of an antihypertensive agent since the major studies of beta-adrenoceptor blockers or thiazide diuretics. The results of this study are awaited with considerable interest.
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PMID:Endothelial dysfunction and hypertension. 903 53

The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.
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PMID:Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition. 919 84

Agonists acting on the vascular endothelium can modulate the release of a number of factors that interact with the surrounding smooth muscle cells and influence their tone. One such factor is the vasoconstricting agent endothelin-1 (ET-1), which has been implicated in several disease states, including stroke. However, very little is known about the physiological role of ET-1 in the cerebral circulation. We demonstrate that activation of alpha2-adrenoceptors in human pial artery endothelial cells reduces both constitutive and agonist-stimulated release of immunoreactive ET-1. That this has physiological relevance is supported by our demonstration that in segments of rabbit middle cerebral arteries, alpha2-adrenoceptor activation reduces the release of endothelium-derived ET-1 and causes an endothelium-dependent relaxation. The adrenoceptor-dependent relaxation was not blocked by combined addition of indomethacin and N omega-nitro-L-arginine in 25 mmol/L KCl-depolarizing physiological solution but was selectively antagonized by a subthreshold concentration of exogenous ET-1. Our data suggest that activation of endothelial alpha2-adrenoceptor would favor a decrease in ET-1 production and possibly promote vascular relaxation.
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PMID:Reversal of endothelin-1 release by stimulation of endothelial alpha2-adrenoceptor contributes to cerebral vasorelaxation. 933 80


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