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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown previously that clenbuterol, a beta 2-adrenergic receptor agonist, enhances NGF synthesis in adult rat brain. Since NGF is able to protect neurons against damage, we tried to find out whether clenbuterol can rescue cultured hippocampal neurons from excitotoxic damage by induction of NGF. The neuroprotective activity of clenbuterol on neurons in the vulnerable CA1 subfield of the hippocampus was tested in a rat model of transient forebrain ischemia. Additionally, in the mouse model of focal cerebral ischemia the ability of clenbuterol to reduce the infarct size was examined. Exposure of mixed neuronal/glial hippocampal cultures to clenbuterol (1 to 100 microM) enhanced significantly the content of NGF measured in the culture medium by two-site ELISA. The excitotoxic injury was induced in the same type of cells after 14 days in vitro by exposure to 1 mM L-glutamate for 1 h in serum-free medium. NGF itself (0.15 to 100 ng/ml) added to the growth medium 4 h before until 18 h after induction of injury (the point of glutamate-toxicity measurement), protected hippocampal neurons from excitotoxic damage. Clenbuterol (1 to 100 microM) provided similar neuroprotection as NGF under the same experimental conditions. The neuroprotective activity of clenbuterol (100 microM) against glutamate-induced damage in hippocampal cultures was blocked by anti-NGF monoclonal antibodies (0.5 microgram/ml) added to the medium during the clenbuterol exposure, demonstrating that the neuronal rescue is mediated by NGF. Propranolol, a beta-adrenergic receptor antagonist (10 microM) added 20 min before and kept in the medium during exposure of the cultures to clenbuterol (1 microM) reversed the neuroprotective activity, suggesting that the induction of NGF and neuroprotection caused by clenbuterol are mediated via beta-adrenergic receptor activation. The capacity of clenbuterol to protect hippocampal neurons was also demonstrated in vivo in a rat model of transient forebrain ischemia. Clenbuterol (4 x 1 mg/kg) administered intraperitoneally increased the number of viable neurons in CA1 subfield of the rat hippocampus. Furthermore, clenbuterol (0.3 and 1 mg/kg, i.p. and 1 mg/kg, s.c.) reduced significantly the infarct area on the mouse brain surface after occlusion of the middle cerebral artery. The present data demonstrate that clenbuterol induces NGF synthesis in cultured hippocampal cells and protects hippocampal neurons from excitotoxic damage. The neuroprotective activity of clenbuterol is also demonstrated in vivo in two rodent models of cerebral ischemia. The results offer strong evidence that the neuroprotective activity of clenbuterol is caused by activation of beta-adrenergic receptors and the subsequent increased expression of NGF.
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PMID:Clenbuterol protects mouse cerebral cortex and rat hippocampus from ischemic damage and attenuates glutamate neurotoxicity in cultured hippocampal neurons by induction of NGF. 873 52

Propranolol has been shown to be effective for as long as 5 days in massively burned children to reduce heart rate and cardiac work. This article describes the use of propranolol given for 10 days to burned children to test whether the drug remains effective and safe in reducing heart rate and cardiac work for longer periods. We prospectively studied 22 children, 1 to 10 years of age with burns covering > or = 40% of their total body surface area. These children were treated with 0.5 to 1.0 mg/kg propranolol given orally or intravenously every 8 hours for 10 days. In both septic and nonseptic patients, propranolol significantly decreased their daily average heart rate (between 10% and 13%, p < 0.05) and rate-pressure product (between 10% and 16%, p < 0.05) compared with their 24-hour mean before propranolol treatment. No significant change in mean arterial blood pressure, or plasma urea nitrogen creatinine or glucose levels could be shown. No hypotension, hypothermia, azotemia, hyperglycemia or hypoglycemia, arrhythmia, bronchospasm, or peripheral ischemia was noted during or after treatment. Whereas propranolol lowered heart rate more per milligram per kilogram body weight when given intravenously, both routes were safe and effective. From these data, we conclude that propranolol can be given to decrease the work of the heart safely and effectively for > or = 10 days.
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PMID:Prolonged use of propranolol safely decreases cardiac work in burned children. 916 45

To determine whether prior acute Beta blockade protects the heart against the deleterious effects of normothermic low flow global ischemia on myocardial function, aortic pressure, developed pressure, dP/dtmax and end diastolic pressure were monitored in isolated perfused rabbit hearts prior to, during and following 30 and 60 min ischemia, during which either Krebs-Henseleit (control) or Beta blocking agents. Bevantolol (cardioselective) or Propranolol (non-selective) were perfused through the heart. Control hearts made ischemic for 30 min and then reperfused had significantly elevated end diastolic (p < .01) and aortic pressures (p < .01) and reduced developed pressure relative to baseline (p < .05). Hearts treated with Bevantolol or Propranolol (3 x 10(-5) m/l) 5 min prior to and during 30 min ischemia recovered preischemic developed pressure and dP/dtmax (p > 0.05), while end diastolic pressure was elevated (p < .01, p < .05 respectively). Aortic pressure was unchanged relative to baseline (p > .05). Comparison of indices from hearts under Beta blockade with controls showed that following 30 min ischemia and recovery, the Bevantolol treated group had reduced aortic pressure (p < .01) and end diastolic pressure (p < .05) and increased percent developed pressure and percent dP/dtmax (p < .001) relative to control. In the propranolol treated group, end diastolic pressure was reduced and percent developed pressure (p < .01) and percent dP/dtmax (p < .001) were increased relative to unblocked hearts. Following 60 min ischemia and 30 min reperfusion, reduction in all functional indices occurred, however dP/dtmax was unchanged from baseline in the Propranolol and Bevantolol treated groups. Comparison between groups showed that the Bevantolol treated group had significantly better dP/dtmax and developed pressure (p < .05), whereas the Propranolol group shows no significant difference from baseline (p > .05) (K-H). We conclude that following short periods of ischemia, Beta blockade protects the heart from deleterious function effects of ischemia but that the protective effect is diminished in Bevantolol relative to Propranolol treatments following prolonged ischemia. The data indicates that the beneficial effects of Beta blockade in reducing ischemic induced damage occurs early during conditions of ischemia such as would be present in the setting of acute myocardial infarction.
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PMID:Myocardial functional preservation during ischemia: influence of beta blocking agents. 940 63

Our objective was to investigate the effects of alpha1- or beta-adrenoceptor blockers on endocardial and epicardial refractory-period changes during myocardial ischemia in alpha-chloralose-anesthetized dogs. The first and second diagonal branches of the left anterior descending coronary artery were ligated. The refractory period was determined by an S1-S2 extrastimulus method. Dogs were treated with the alpha1-blocker bunazosin (0.1-0.2 mg/kg, i.v.; n = 16), the beta-blocker propranolol (0.2 mg/kg, i.v.; n = 15), or saline (n = 11). Dogs that developed ventricular tachycardia/fibrillation (VT/VF) during the experiment were excluded from the statistical assessment in refractory periods. In all groups, coronary ligation produced a significant shortening of the refractory period of ischemic epicardial tissue (p < 0.05) but only minimal shortening of ischemic endocardial refractory periods, resulting in an increased difference in repolarization time between the endo- and epicardial sites. Treatment with bunazosin ameliorated this ischemia-related shortening of refractory periods at both the endo- and epicardial sites, with a greater effect seen epicardially (p < 0.05), resulting in values similar to those in the nonischemic tissue. Treatment with propranolol prolonged refractory periods more in the epicardial (p < 0.01) than in endocardial sites, exacerbating the disparity in the refractory period between the endo- and epicardial sites (p < 0.05). Propranolol also prolonged the refractory period of nonischemic tissue (p < 0.05 and p < 0.01 in endo- and epicardial sites, respectively), resulting in a significant difference between the ischemic and normal myocardium at the endocardial site (p < 0.05). Results suggest that the alpha1-blocker bunazosin reduces the refractory-period disparity between the ischemic and normal myocardium without increasing the disparity between the endo- and epicardial surfaces, whereas propranolol produces a greater disparity.
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PMID:Differences in refractory-period response of canine subendocardium and subepicardium to bunazosin, an alpha1-adrenoceptor antagonist, and propranolol during myocardial ischemia. 943 24

Carvedilol, a new vasodilating beta-adrenoceptor antagonist and a potent antioxidant, produces a high degree of cardioprotection in a variety of experimental models of ischemic cardiac injury. Recent clinical studies in patients with heart failure have demonstrated that carvedilol reduces morbidity and mortality and inhibits cardiac remodeling. The present study was designed to explore whether the protective effects of carvedilol on the ischemic myocardium include inhibition of apoptosis of cardiomyocytes and, if so, to determine its mechanism of action. Anesthetized rabbits were subjected to 30 minutes of coronary artery occlusion followed by 4 hours of reperfusion. Detection of apoptosis of cardiomyocytes was based on the presence of nucleosomal DNA fragments on agarose gels (DNA ladder) and in situ nick end labeling. Carvedilol (1 mg/kg IV), administered 5 minutes before reperfusion, reduced the number of apoptotic myocytes in the ischemic area from 14.7 +/- 0.4% to 3.4 +/- 1.8% (77% reduction, P<.001). Propranolol, administered at equipotent beta-blocking dosage, reduced the number of apoptotic myocytes to 8.9 +/- 2.1% (39% reduction, P<.05). DNA ladders were observed in the hearts of all six vehicle-treated rabbits but only one of six carvedilol-treated rabbits (P<.01). Immunocytochemical analysis of rabbit hearts demonstrated an upregulation of Fas protein in ischemic cardiomyocytes, and treatment with carvedilol reduced both the intensity of staining as well as the area stained. Myocardial ischemia/reperfusion led to a rapid activation of stress-activated protein kinase (SAPK) in the ischemic area but not in nonischemic regions. SAPK activity was increased from 2.1 +/- 0.3 mU/mg (basal) to 8.9 +/- 0.8 mU/mg after 30 minutes of ischemia followed by 20 minutes of reperfusion. Carvedilol inhibited the activation of SAPK by 53.4 +/- 6.5% (P<.05). Under the same conditions, propranolol (1 mg/kg) had no effect on SAPK activation. Taken together, these results suggest that carvedilol prevents myocardial ischemia/reperfusion-induced apoptosis in cardiomyocytes possibly by downregulation of the SAPK signaling pathway, by inhibition of Fas receptor expression, and by beta-adrenergic blockade. The former two actions represent novel and important mechanisms that may contribute to the cardioprotective effects of carvedilol.
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PMID:Possible involvement of stress-activated protein kinase signaling pathway and Fas receptor expression in prevention of ischemia/reperfusion-induced cardiomyocyte apoptosis by carvedilol. 946 87

We compared the cardioprotective effects during experimental ischemia and reperfusion of beraprost sodium (beraprost), a prostacyclin analog, with those of propranolol and diltiazem. Coronary perfused guinea-pig right ventricular free wall preparations were subjected to 30 min no-flow ischemia with or without drugs, followed by 60 min reperfusion without drugs. In control preparations, decrease in contractile force and increase in resting tension were observed during the no-flow period. On reperfusion, contractile force returned to less than 50% of preischemic values. Beraprost, at 0.1 microM, showed no inotropic effect under normoxic condition and during the no-flow period, but significantly enhanced the recovery of contractile force after reperfusion to about 80% of control values. Propranolol (30 microM) or diltiazem (10 microM) produced similar enhancement of recovery of contractile force after reperfusion, but these two drugs decreased the contractile force under normoxic conditions to less than 20% of control values. Thus, the cardioprotective effect of beraprost was different from those of propranolol and diltiazem in that it was not accompanied by cardiosuppressive effects.
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PMID:Cardioprotective effects of beraprost sodium against experimental ischemia and reperfusion as compared with propranolol and diltiazem. 959 26

The regulatory mechanisms of the cerebral blood flow have preoccupied the physiology department of Cluj since the end of the 4th decade. These studies continued over the last years. The researches progressed from the studies of regulation by blood pressure changes to the nervous regulation and to the metabolic one. This paper's subject is the renin-angiotensin and adrenalin system influence on the changes of cerebral blood flow during the general hypoxic hypoxia and cephalic ischemia. Experiments were performed in 10 dogs anaesthetised with a mixture of chloralose, urethan and morphine. Hypoxic hypoxia was obtained by breathing a mixture of 11% oxygen in nitrogen, in a closed system and cerebral ischemic hypoxia by partial compression of the carotid arteries, after the ligation of the vertebral and thyroid arteries. The arterial blood pressure and the cerebral and hypothalamic blood flow, measured with the heated thermoelement, were registered. The plasma renin activity was tested radioimmunologically before, at 1.5 min, 5, 10 and 15 min, after the beginning of hypoxia. In ischemic hypoxia the experiment was repeated after venous perfusion with propranolol (0.6 mg/kg/h). The systemic blood pressure increased in both forms of hypoxia. The cortical and hypothalamic blood flow increased with the systemic arterial blood pressure. The hypothalamic blood flow remained stable or diminished a little. Propranolol increased the cerebral blood flow during ischemic hypoxia up to 300%. The i.v. administration of angiotensin (1-5 mg/kg) increased the cortical flow, while the hypothalamic flow remained self-regulated. Plasma renin activity increased more in general hypoxic hypoxia, than in cephalic ischemic hypoxia. After propranolol the increase was higher in this hypoxia. Propranolol produced a major activation of the renin-angiotensin system and of the cortical blood flow in ischemic cephalic hypoxia, the renin-angiotensin system being located in the cerebral structure. As well high doses of angiotensin produced cerebral vasodilatation in small cerebral vessels. This effect was found in our experiments in the cortical blood flow too. Our results indicate a beneficial propranolol effect on cortical circulation in ischemic hypoxia.
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PMID:The renin-angiotensin system and the effect of propranolol upon the cerebral cortical and hypothalamic circulation in hypoxia. 965 7

Propranolol, a beta-adrenergic blocking agent commonly used in the treatment of hypertension, decreases mesenteric blood flow during exercise, at rest, and in cirrhosis. Widespread idiopathic myointimal hyperplasia of mesenteric veins produces intestinal ischemia in otherwise healthy individuals. This report describes a 42-year-old woman who died suddenly and unexpectedly while attending a ball game. She had hypertension treated with propranolol and no other clinically apparent disorders. Autopsy revealed mild mesenteric venous myointimal hyperplasia and segmental jejunal infarction. Recent clinical and experimental studies are used to propose possible mechanisms for this death which combine the effects of propranolol and mesenteric venous myointimal hyperplasia.
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PMID:Unexpected sudden death during propranolol therapy in a patient with mild mesenteric venous myointimal hyperplasia. 967 May 18

We investigated the response of refractory periods and blood flow to blockade of alpha 1- and beta-adrenoceptors alone, or in combination on endocardium and epicardium, during myocardial ischemia. Dogs were anesthetized with alpha-chloralose and divided into bunazosin (an alpha 1-blocking agent)-treated (0.1-0.2 mg/kg, i.v., n = 14), propranolol-treated (0.2 mg/kg, i.v., n = 12), and vehicle-control (n = 10) groups. The diagonal branches of the left anterior descending artery were ligated. The refractory period (ERP) and blood flow (RMBF) were determined by an S1-S2 extrastimulus method and a nonradioactive microsphere technique, respectively. The duration of regional electrograms (DRE) was measured in the endocardial and epicardial sites. Bunazosin alone reversed the ischemia-related shortening of ERPs at both the endocardial and epicardial sites, with a greater effect seen epicardially (P < .05). Subsequent administration of propranolol further prolonged ERPs in both sites, although the effect was greater in the epicardial surface (P < .05). Bunazosin reduced RMBF to a greater degree at the endocardial site than at the epicardial site in the ischemic zone (P < .01 and P < .05, respectively), but the magnitude of the reduction in RMBF and the difference in RMBF between sites were similar to the control group (P < .01). Propranolol alone and subsequent administration of bunazosin prolonged the ERP more at the epicardial site (P < .01) than at the endocardial sites in the ischemic zone. Propranolol produced no significant difference in RMBF between both sites. DREs in animals treated with bunazosin and propranolol alone, or in combination, were similar to those in animals treated with vehicle. These results suggest that differences in ERPs between endocardium and epicardium with blockade of alpha 1- and/or beta-adrenoceptor are not due to concomitant alterations in RMBF, but to differences in electrophysiological properties of the endocardial and epicardial cells during the acute phase of myocardial ischemia.
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PMID:Disproportional response between refractory period and blood flow to alpha 1- and beta-adrenoceptor blockade in canine ischemic myocardium. 1041 Aug 26

This study was undertaken to define the contributions of left ventricular hypertrophy (LVH) and increased adrenergic activity to the acceleration of ischemic contracture (IC) that occurs in chronic hyperthyroid rat heart. Acute and chronic hyperthyroidism (THYR) were induced by thyroxine administration for 2 and 14 days, respectively, and normal animals (NORM) served as controls. Isolated hearts were perfused in a Langendorff mode. NORM alpha acute, n = 6; THYR alpha acute, n = 8; and THYR alpha, n = 13; and NORM alpha, n = 13 were subjected to 20-min zero-flow global ischemia (I) and 45-min reperfusion (R). Additional THYR and NORM hearts treated with propranolol (prop) were subjected to 30-min I; THYR beta prop, n = 6 and NORM beta prop, n = 8, and THYR beta, n = 6, NORM beta, n = 8 served as controls. Acceleration of IC was measured by the time to peak contracture (Tmax). Left ventricular hypertrophy (LVH) was assessed by the ratio of left ventricular weight in milligrams (LVW) to animal body weight (BW) in grams. Cardiac hypertrophy developed in chronic but not acute hyperthyroidism. Propranolol reduced the extent of LVH. Contracture occurred earlier in chronic than in acute hyperthyroid and normal hearts. Propranolol did not alter contracture. In conclusion, IC is accelerated by thyroxine administration, and this is probably not due to LVH or increased beta-adrenergic activity. Propranolol diminishes LVH in hyperthyroidism.
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PMID:Propranolol diminishes cardiac hypertrophy but does not abolish acceleration of the ischemic contracture in hyperthyroid hearts. 1097 97


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