Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the influence of selective beta 1-adrenergic blockade, in contrast to beta 1- and beta 2-adrenergic blockade, systemic and coronary hemodynamics were studied. Measurements were made at rest and during exercise in 23 patients with suspected coronary artery disease (CAD) before and after either metoprolol or propranolol, given in doses to provide comparable beta 1-receptor blockade. Quantitative coronary angiography was performed at rest. Using a randomized, double-blind protocol, either beta 1 and beta 2 blockade was produced by propranolol (0.1 mg/kg intravenously), or selective beta 1 blockade was produced by metoprolol (0.15 mg/kg intravenously). As expected, at these doses both drugs produced a comparable decrease in heart rate at rest and during exercise, averaging 9% and 14% after propranolol and 10% and 16% after metoprolol. Exercise duration to ischemia was prolonged in most patients with severe CAD after either propranolol (5 of 7) or metoprolol (6 of 10) treatment. The effects of these 2 beta-blocking drugs on systemic hemodynamic values at rest and during exercise were similar. Additionally, coronary sinus flow was usually unchanged by both drugs at rest (-5% after propranolol and -4% after metoprolol, differences not significant) and decreased a similar amount during exercise (-15% after propranolol and -9% after metoprolol, both p less than 0.05). Coronary resistance did not change significantly with either drug (0% after propranolol and 3% after metoprolol), and during exercise (11% after propranolol and 3% after metoprolol), suggesting that decreases in flow were secondary to reduced demand. Furthermore, neither drug produced detectable changes in coronary artery size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of selective (beta 1) and nonselective (beta 1 and beta 2) beta-adrenergic blockade on systemic and coronary hemodynamic findings in angina pectoris. 288 1

Factors contributing to the development of exercise-induced painful ischemia, such as actions of the central nervous system and catecholamines, have been well identified, but the mechanisms by which nonexercise-related silent episodes of ischemia are provoked are unknown. Possible mechanisms receiving much study in recent years are those having the potential to influence the myocardial oxygen supply-demand relation. Beta-adrenergic receptor stimulations, by increasing myocardial oxygen demand through augmentation of heart rate and contractility (beta 1), may mediate responses that cause ischemia or perpetuate ischemic episodes induced by other means. Other receptors (beta 2) may mediate coronary and peripheral vascular constriction, limiting myocardial oxygen supply and further increasing myocardial oxygen demand. Studies have investigated the effect of beta blockade on ischemic episodes in patients with a variety of clinical forms of coronary heart disease. Beta blockade has been shown to reduce the frequency and duration of silent and painful ischemic episodes in patients with effort angina and rest angina. The data suggest that heart rate and perhaps other changes observed with use of beta blockade play an important role in silent ischemia; heart rate at specific times throughout the day, particularly in the late A.M., and the increase in heart rate seen in conjunction with silent ischemic episodes are all decreased with administration of beta blockade. Results of a recent study focusing only on silent ischemia showed that beta-blocker treatment with metoprolol, compared with placebo, significantly reduced total silent ischemic time (frequency and duration of episodes) in all periods examined.
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PMID:Beta-adrenergic blockers in silent myocardial ischemia. 289 28

Platelets are believed to play a role in the pathogenesis of atherosclerosis and of the vascular obstruction that causes the acute complications of coronary artery disease. Since specific behavioral patterns appear to be related to the development of coronary artery disease and since emotional stress may predispose an individual to acute cardiovascular ischemia, it was hypothesized that platelet activation by catecholamines might be involved in these events. To study emotional stress, plasma samples were obtained from 61 senior medical residents immediately before they were to speak in public. There were significant increases in the plasma concentrations of the platelet-secreted proteins platelet factor 4 and beta-thromboglobulin and epinephrine and norepinephrine immediately before speaking, which demonstrates that platelet activation and secretion occur in association with this type of emotional stress. Four trials were carried out to study the mechanism for this observed platelet secretion: (1) phenoxybenzamine, (2) propranolol, (3) 650 mg aspirin, and (4) 80 mg aspirin were given several hours before the public speaking engagement. Neither phenoxybenzamine nor propranolol in doses that blocked the hemodynamic effects of alpha 1- and beta 1-adrenergic stimulation modified platelet secretion. Aspirin also did not block platelet secretion, which suggests that platelets were not being stimulated through a cyclooxygenase-dependent pathway. This study provides direct evidence of platelet secretion in vivo in association with emotional stress, and underscores the potential importance of platelet activation and secretion in the acute events that occur in patients with vascular disease.
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PMID:Platelet activation and secretion associated with emotional stress. 298 76

The EEG power spectral analysis of 8 patients with a definite sylvian ischemia, the standard EEG of which was normal, was determined in comparison with the date of a control group (N = 14). We calculated the right-left power spectral differences in 4 symmetrical bipolar leads for 5 rhythms (delta: 1.2-3.1 Hz, theta: 3.5-7 Hz, alpha: 7.4-12.3 Hz, beta 1: 12.9-14.1 Hz and beta 2: 15.2-17.2 Hz). For each patient, the spectral difference is measured in comparison with the normal range of the control group with an alpha risk of 5%. There are 54 asymmetries favouring the lesioned side (mostly in 5 patients) and 6 the opposite, without predominance of a particular rhythm with the exception of the beta 2 rhythm which presents no asymmetries.
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PMID:[EEG spectral analysis in sylvian ischemia with normal value tracings]. 342 85

The kinetics of protein kinase C (PKC) translocation and down-regulation in the 20-day-old fetal brain following short and long episodes of maternal-fetal blood flow occlusion were examined. Restriction for up to 15 min increased the specific enzymatic activity in the membrane by 73%, indicative of translocation. After a 30-min restriction and a 2.5-h reperfusion the total PKC activity in the cytosol was reduced to approximately 50%, consistent with down-regulation/inactivation. The total membrane PKC activity remained unchanged. Several PKC isoenzymes, including alpha, beta 1, beta 2, epsilon, and zeta, but not gamma, were identified in the fetal brain on western blots using specific antibodies. Compared with postnatal day 15, a greater proportion of the fetal PKC isoforms, particularly alpha and epsilon, were membrane bound, alpha, beta 2, epsilon, and zeta, but not beta 1, were translocated into the membrane compartment after episodes of ischemia alone or ischemia and reperfusion. There were no major identifiable proteolytic fragments in the 50-kDa region. Major losses in the total enzymatic activity were encountered in both cytosol and membrane fractions after storage of the enzyme for 10 days at 4 degrees C. These losses were less profound in membrane fractions from ischemic than control animals, suggesting a relative sparing of activity in the membrane as a result of the insult. Preincubation of DEAE-purified PKC for 30 min at 50 degrees C resulted in enzyme inactivation. This was accompanied by a size reduction (approximately 2-5 kDa) in the gel migration of several isozymes in both cytosol and membrane fractions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemia-triggered translocation and inactivation of protein kinase C isoforms in the fetal brain. 759 56

The beneficial effect of chronic beta-blockade in patients with congestive heart failure has been repeatedly shown since its introduction into treatment for this condition in 1975. Still this kind of therapy remains controversial, it is sometimes regarded as a therapeutic paradox, and its use is mainly limited to specialist centers. Various favorable effects of beta-blockers in patients with heart failure due to idiopathic dilated cardiomyopathy and ischemic heart disease have been demonstrated, the principal among them being reduction in energy requirements and ischemia, antiarrhythmogenic effect, improvement of diastolic function, protection of myocytes against catecholamine overload, centrally mediated increase in vagal tone, upregulation of beta-adrenergic receptors, and possible blockade of autoantibodies against beta 1-receptors. Although most of the studies used metoprolol, these effects may be relevant to certain other beta-blockers. Despite very solid pathophysiological and pharmacological rationales for the use of beta-blockade, a major obstacle for a general acceptance of this therapeutic concept is the striking contrast between hemodynamic changes during the acute effect and long-term treatment. When titrated carefully from very low doses and used with a true commitment to long-term treatment, beta-blockers have been shown to prevent further deterioration of heart failure and to improve hemodynamics, exercise tolerance, quality of life, and prognosis.
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PMID:Use of beta-adrenoceptor blockers in patients with congestive heart failure. 766 94

Transforming growth factors beta are multifunctional proteins and regulators of cell proliferation and differentiation. Transforming growth factor-beta s have the capacity to rescue adult neurons from ischemia- and glutamate-induced cell death and are prominent in the embryonic and adult brain including striatum and substantia nigra. In the present study we show that transforming growth factors-beta 1, -2, and -3 promote, in a dose-dependent fashion, in vitro survival of tyrosine hydroxylase-immunoreactive dopaminergic neurons isolated from the embryonic rat mesencephalon floor. The magnitude of the effect, which was half-maximal at a concentration of 20 pM, was identical for all three transforming growth factor-isoforms and matched that of fibroblast growth factor-2. Unlike fibroblast growth factor-2, however, transforming growth factor-beta s did not increase numbers of astroglial cells visualized by using antibodies to glial fibrillary acidic protein, and had no effect on cell proliferation monitored by incorporation of BrdUrd. Transforming growth factor-beta s were significantly more potent than fibroblast growth factor-2 in protecting dopaminergic neurons against N-methyl-4-phenylpyridinium ion toxicity. RT-PCR analysis indicated that the effect of transforming growth factor-beta s is not mediated by glial cell-derived neurotrophic factor, which was not detectable in cultures at various time points. On the other hand transforming growth factor-beta 2 mRNA could be detected in freshly isolated and cultured mesencephalic cells, and its immunoreactivity has also been demonstrated in the embryonic day 14 mesencephalon floor. We conclude that transforming growth factor-beta has trophic and protective effects on developing dopaminergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transforming growth factor-beta promotes survival of midbrain dopaminergic neurons and protects them against N-methyl-4-phenylpyridinium ion toxicity. 770 May 16

Acute myocardial ischemia leads to a rapid increase of cardiac beta-adrenergic receptors in plasma membranes despite the release of large and desensitizing amounts of endogenous catecholamines. Part of this increase has been shown to occur at the expense of intracellular receptors. To investigate whether an additional expressional regulation of beta-adrenergic receptors due to an increase of mRNA levels is involved, the mRNA levels specific for beta 1- and beta 2-adrenergic receptors were determined after various periods of global ischemia in isolated perfused rat hearts. The subtype-specific quantification of mRNA for beta 1- and beta 2-adrenergic receptors was determined using reverse-transcription followed by PCR (RT-PCR) and RNA protection assays. RT-PCR resulted in single amplification products of the expected sizes (159 bp for beta 1-adrenergic receptors and 240 bp for beta 2-adrenergic receptors). The specificity of these amplification products was confirmed by specific restriction digests. Southern blot hybridizations with internal oligonucleotides and sequencing using the dideoxy chain termination method. For quantification purposes, the mRNAs of housekeeping gene GAPDH and of cardiac alpha-actin were determined as internal standards. Additionally, cRNAs specific for beta 1- and beta 2-adrenergic receptors were used as external standards. Brief periods of global ischemia induced a rapid increase in the steady state level of mRNA for beta 1-adrenergic receptors. There was a statistically significant rise already after 15 min by 57% compared to controls. After 30 min of ischemia the mRNA levels had almost doubled. After 60 min of ischemia, the mRNA levels specific for beta 1-adrenergic receptors tended to decrease, but remained significantly above normoxic controls. In contrast, the mRNA levels specific for beta 2-adrenergic receptors remained constant up to 60 min of global myocardial ischemia. To investigate, whether agonist occupancy of the receptors may contribute to this regulation, the effect of preperfusion with the beta-blocker alprenolol was determined. Contrary to expectation, beta-blockade did not influence the ischemia-induced increase of mRNA levels specific for beta 1-adrenergic receptors. These data demonstrate for the first time, that acute myocardial ischemia induces a rapid, and subtype-selective regulation of mRNA levels for beta 1-adrenergic receptors. However, occupation or activation of beta-adrenergic receptors by an agonist is not involved in this newly characterized regulation of mRNA for beta 1-adrenergic receptors in acute myocardial ischemia.
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PMID:Regulation of beta-adrenergic receptors in acute myocardial ischemia: subtype-selective increase of mRNA specific for beta 1-adrenergic receptors. 776 Mar 63

Antiarrhythmic effects of nebivolol, a cardioselective beta 1-adrenoceptor blocker facilitating vascular release of nitric oxide (NO), were investigated in different experimental models. In the reperfusion-induced arrhythmias after 5 min of left coronary artery ligation in rats, nebivolol 1.25 mg/kg intravenously (i.v.) reduced the incidence of ventricular tachycardia (VT) from 85% in the solvent group to 33% (p < 0.05) and decreased that of ventricular fibrillation (VF) to 20% vs. 67% in the solvent group, (p < 0.05). In ischemia-induced arrhythmias resulting from 20-min coronary artery ligation in rats, nebivolol 1.25 mg/kg i.v. reduced the incidence of VT to 50% as compared with 87% in the solvent group and decreased the incidence of VF to 17% as compared with 67% in the solvent group (p < 0.05). In electrically stimulated hearts in open-chest guinea pigs, nebivolol produced a dose-dependent (0.16-2.5 mg/kg i.v.) increase in VF threshold (VFT). In guinea pigs with ouabain-induced cardiotoxicity, nebivolol 1.25 mg/kg i.v. (n = 7) doubled the doses of ouabain required to provoke toxic ECG changes as compared with those in the solvent-pretreated group. In rats with aconitine-induced cardiac toxicity, nebivolol 1.25 mg/kg i.v. significantly reduced the incidence of ventricular arrhythmias. Our results demonstrate that nebivolol suppresses arrhythmias in various experimental models in vivo.
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PMID:Antiarrhythmic effects of nebivolol in experimental models in vivo. 789 84

Mortality is high among patients developing post-traumatic brain oedema and increased intracranial pressure following severe head injury. Although routine treatment varies from one centre to another it often includes one or more of such measures as hyperventilation, high-dose barbiturate therapy, osmotherapy or the drainage of cerebrospinal fluid. The preservation of high cerebral perfusion pressure is fundamental to traditional treatment, often combined with inotropic support, as ischemia is considered to be a crucial factor with regard to the development of secondary injuries and oedema in the brain. In the article is described a new treatment of posttraumatic brain oedema, based on the hypothesis that the development of oedema is instead largely due to disturbance of brain volume control mechanisms resulting from increased permeability of the semi-permeable blood-brain barrier. If this hypothesis is true, oedema therapy should include measures to decrease hydrostatic capillary pressure and preserve normal colloid osmotic pressure. Our new therapy therefore includes hypotensive treatment in the form of beta 1-blockade and alpha 2-stimulation and precapillary vasoconstriction by dihydroergotamine (DHE) infusion, all of which reduce capillary pressure. The DHE may also constrict venous vessels, resulting in reduced blood volume. Colloid osmotic pressure is preserved with albumin infusion. Normovolemia is attained despite manifest fluid balance. With this therapy both mortality and morbidity have been reduced significantly, as compared to retrospective figures for a comparable control group.
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PMID:[Current alternative therapy of post-traumatic brain edema]. 791 Jun 83


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