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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of experiments have been done to investigate the role of oxygen free radicals in ischemia/reperfusion injury. The following results were found: Myocardial MDA content increased significantly after post-ischemic reperfusion in vivo and in vitro. A blockade of the xanthine oxidase pathway for free radical generation could provide effective protection against ischemia/reperfusion injury. Exogenous reactive oxygen intermediates H2O2, .OH and O2- could induce changes in the contractility and electrophysiological properties of myocardial cells similar to those seen in ischemia/reperfusion. An outburst of free radical generation was detected by ESR spectroscopy at low temperature (-173 degrees C) and with the spin trapping technique during the very early phase of reperfusion. The authors emphasize the important role of free radicals in the pathogenesis of myocardial ischemia/reperfusion injury.
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PMID:The role of oxygen free radicals in myocardial ischemia/reperfusion injury. 179 73

Although oxygen free radicals have been implicated as mediators of cellular injury in myocardial ischemia-reperfusion, the exact nature of defects produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is involved in the efflux of Ca2+ from the cell, this study was undertaken to examine the effects of oxygen free radicals on sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation of membrane phospholipids. Isolated rat heart sarcolemmal membranes were incubated with xanthine + xanthine oxidase [a superoxide anion radical (O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical (HO.)-generating system] and assayed for Ca2+-pump activities. O2- inhibited the Ca2+-pump activities in a time-dependent manner; a significant inhibition of Ca2+-stimulated ATPase activity was seen after 1 min of incubation. Superoxide dismutase showed a protective effect on depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump activities in a dose-dependent manner; this inhibition was protected by the addition of catalase. HO. depressed the Ca2+-pump activities to a greater extent in comparison with H2O2. Mannitol showed a protective effect on HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid peroxidation by free radicals was evident from increased formation of malondialdehyde. These results indicate that the sarcolemmal membrane is altered on exposure to oxygen free radicals, and this may result in depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial cell.
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PMID:Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals. 253 32

The pathways for the metabolism of molecular oxygen involve one electron-transfer reaction with the subsequent production of reduced-oxygen intermediates. These reduced-oxygen intermediates include the superoxide anion (.O2-), hydrogen peroxide (H2O2), and the hydroxyl radical (.OH), which are highly reactive, short-lived species. Normally intracellular enzyme systems that include superoxide dismutase, catalase, and glutathione peroxidase are responsible for "scavenging" these products of oxygen metabolism. However, in many pathological states such as inflammation, ischemia, and reperfusion, there is an increased production of these reduced-oxygen intermediates, which are capable of extensive tissue damage. It is the purpose of this symposium to examine, in depth, the role of oxygen free radical systems as mediators of myocardial dysfunction and expand our knowledge of myocardial ischemia, ischemia-reperfusion injury, and the inflammatory response of the myocardium.
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PMID:The oxygen free radical system and myocardial dysfunction. 298 5

The monovalent reduction of oxygen yields two reduced intermediate forms: the dioxide anion (O2), hydrogen peroxide H2O2, and the hydroxyl radical (OH.) several of which appear as radicals. Under normal conditions, the concentration of free oxygen radicals in the tissues is closely controlled because of the serious cell lesions which an accumulation of these radicals can cause. The aim of this paper was to discuss the origin and role of free oxygen radicals in cell lesions induced by myocardial ischemia/perfusion as well as results obtained in different experimental models using methods to trap these radicals. Overall these experimental results are encouraging and appear to offer new therapeutic possibilities which, however, have been evaluated only barely in man.
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PMID:[Role of free radicals in ischemia and myocardial reperfusion. The oxygen paradox]. 366 84

Activation of cardiac sympathetic afferents leads to excitatory cardiovascular reflexes and pain during myocardial ischemia. We hypothesized that cardiac sympathetic afferents are activated by reactive oxygen species produced during ischemia and reperfusion. Single-unit nerve activity of 55 afferents was recorded from the left paravertebral sympathetic chain (T1-T4) in cats anesthetized with alpha-chloralose. Receptive fields of all afferents were located on the right or left ventricle. Mechanical and chemical sensitivities of each afferent ending were evaluated by von Frey hairs, cardiac distension, and local application of bradykinin (BK, 142 pmol) or H2O2 (7.5-15 mumol) to the receptive field. Thirty-one afferents (56%) were responsive to bradykinin (BK), H2O2, and ischemia (2 or 10 min). Deferoxamine (Def, 10-100 mg/kg), dimethylthiourea (DMTU, 10-100 mg/kg), or iron-loaded Def (10 mg/kg) were employed to evaluate the role of H2O2 and hydroxyl radicals (.OH) in activating these afferents (10A delta and 21C fibers) during ischemia and reperfusion. Treatment with the nonspecific scavenger DMTU (n = 10) significantly diminished the increase in discharge activity evoked by ischemia and reperfusion. Treatment with Def also significantly attenuated the responses during ischemia and reperfusion. Thus reactive oxygen species, particularly .OH, activate a group of cardiac sympathetic A delta- and C-fiber afferents during myocardial ischemia and reperfusion and may play an important role in mediating cardiovascular sympathetic reflex responses and/or pain transmission.
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PMID:Ischemia- and reperfusion-sensitive cardiac sympathetic afferents: influence of H2O2 and hydroxyl radicals. 757 32

We have shown previously that reactive oxygen species stimulate abdominal sympathetic afferents to cause reflex cardiovascular activation. Because myocardial ischemia and reperfusion also generate reactive oxygen species, we investigated the possibility that cardiovascular reflexes could be induced by topical application of H2O2 to the anterior or posterior ventricular surface in cats anesthetized with alpha-chloralose. Mean arterial pressure (MAP), heart rate (HR), left ventricular (LV) pressure, aortic flow (AF), and first derivative of LV pressure at 40 mmHg developed pressure (LV dP/dt40) were monitored. H2O2 (44 and 130 mumol) significantly increased MAP but not HR or LV dP/dt40 in intact cats (n = 8). Application of H2O2 (44 mumol) significantly increased MAP (129 +/- 9 to 152 +/- 10 mmHg), HR (240 +/- 11 to 245 +/- 10 beats/min), AF (191 +/- 13 to 212 +/- 17 ml/min), total peripheral resistance (0.68 +/- 0.13 to 0.73 +/- 0.04 peripheral resistance units), and LV dP/dt40 (2,666 +/- 145 to 3,012 +/- 205 mmHg/s) after bilateral cervical vagotomy (n = 6). These H2O2-induced excitatory responses were abolished after bilateral T1-T4 ganglionectomy. In six additional cats, H2O2 (44 mumol) significantly decreased MAP (114 +/- 5 to 102 +/- 5 mmHg), HR (207 +/- 7 to 190 +/- 7 beats/min), and LV dP/dt40 (2,776 +/- 168 to 2,600 +/- 153 mmHg/s) after sympathectomy. These depressor responses were eliminated after vagotomy. The magnitude of the cardiovascular reflexes was increased or decreased in a dose-dependent fashion in vagotomized or sympathectomized cats, respectively, over a range of 440 nmol to 44 mumol H2O2. Application of H2O2 to the anterior or posterior ventricular surface resulted in similar pressor or depressor reflexes. Dimethylthiourea and deferoxamine abolished pressor or depressor responses evoked by H2O2 in both vagotomized (n = 8) and sympathectomized (n = 8) cats. We conclude that reactive oxygen species, particularly the hydroxyl radical, can participate in activating cardiac afferents responsible for reflex cardiovascular responses during myocardial ischemia and reperfusion. An inhibitory reflex is transmitted through vagal afferents, whereas an excitatory reflex is conducted by sympathetic cardiac afferents.
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PMID:Cardiac-cardiovascular reflexes induced by hydrogen peroxide in cats. 777 62

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are well known to be produced during prolonged ischemia and reperfusion, contribute to this excitation. Hydroxyl radicals derived from hydrogen peroxide (H2O2) activate abdominal sympathetic afferents and produce reflex excitation of the cardiovascular system. However, it is not known whether inhibitory vagal cardiac afferents are activated by oxygen-derived free radicals. We recorded activity from 52 single vagal afferent fibers in 29 rats; the endings of these fibers were located in the walls of all four chambers of the heart. Thirty-three (63%) of these fibers were classified as chemosensitive C-fiber endings because of their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1 to 10 micrograms) to the surface of the heart encompassing the receptive field, and their conduction velocities. Fourteen (27%) of the remaining fibers were found to be mechanoreceptors. Topical application of H2O2 to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. Activity increased by 498% at a dose of 3 mumol (P < .001). This effect was reproducible and dose dependent and was not due to [H+]. Topical application of xanthine/xanthine oxidase (20 mmol/0.03 mU) activated 8 of the 12 chemosensitive fibers tested and had no direct effect on mechanosensitive fibers. Activity increased by 287% (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of cardiac vagal afferents by oxygen-derived free radicals in rats. 815 36

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are known to be produced during prolonged ischemia and reperfusion, contribute to this afferent excitation. We recorded activity from 47 chemosensitive vagal afferent fibers in 31 rats; the endings of these fibers were located in the left ventricle. Chemosensitive endings were identified with topical applications of capsaicin (10 micrograms) to the surface of the heart. Reactivity of the endings to oxygen-derived free radicals was assessed by topical application of H2O2 (3 to 9 mumol). Activity of the vagal fibers was recorded during 30 minutes of occlusion of the left anterior descending coronary artery (LAD) and 10 minutes of subsequent reperfusion. The activity of chemosensitive endings within the ischemic zone increased in the first 2 minutes of LAD occlusion from 2.2 +/- 0.4 to 4.3 +/- 0.9 impulses per second (107 +/- 30% increase, P < .05). This increased activity waned after 3 to 5 minutes of occlusion. Endings outside the ischemic zone did not increase, their activity at the beginning of ischemia. Reperfusion caused a rapid elevation of activity only in chemosensitive fibers whose endings were found to respond to topical H2O2. The reperfusion-sensitive endings were located both within and outside the ischemic zone of the left ventricle. Indomethacin (5 mg/kg i.v., 20 minutes before occlusion) effectively prevented activation of chemosensitive afferent endings at the beginning of LAD occlusion regardless of their sensitivity to H2O2 but had no effect on the activation at reperfusion.
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PMID:Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins versus oxygen-derived free radicals. 815 37

Because of its potential importance in injury during myocardial ischemia and reperfusion, we assessed mechanisms of hydrogen peroxide (H2O2) cytotoxicity in cultured chick embryo cardiac myocytes. Injury was quantitated by release of lactate dehydrogenase (LDH) or 51Cr, both of which correlated with loss of cell viability assessed by trypan blue exclusion. The iron chelator deferoxamine (0.25-2 mM), but not equimolar iron-loaded deferoxamine, markedly reduced LDH and 51Cr release. Injury was also prevented or attenuated by the diffusible reactive oxygen metabolite scavengers dimethylthiourea (10-20 mM) and N-(2-mercaptopropionyl)-glycine (20 mM). The hydroxyl radical scavenger, dimethyl sulfoxide (200-400 mM), also reduced injury. Other scavengers that probably remained extracellular, superoxide dismutase and mannitol, were ineffective. Thus, with exposure of cardiac myocytes to H2O2, cytotoxicity requires reactions catalyzed by intracellular iron.
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PMID:Hydrogen peroxide cytotoxicity in cultured cardiac myocytes is iron dependent. 830 92

In spite of extensive research during the last decade it has not been possible to prove that endogenously generated hydrogen peroxide or any reduced oxygen species reaches sufficient concentration during reperfusion after myocardial ischemia to contribute significantly to irreversible cell injury. In an attempt to further test this hypothesis we subjected isolated perfused rabbit hearts to 30 min regional ischemia followed by reperfusion and supplied hydrogen peroxide in low levels with or without catalase during the first 30 min of reperfusion and thereafter continued the reperfusion for a total of 120 min. Five different groups were studied: controls, and hearts supplied with 2 microM H2O2, 1 microM H2O2, 1 microM H2O2 + catalase (IU/l) or catalase alone in the initial part of the reperfusion. At the end of 120 min reperfusion, area at risk was measured with fluorescent particles and infarct zone size with tetrazolium staining. The results were: in the control group 32 +/- 5.0% of the risk zone infarcted, in the 2 microM H2O2 group 16.3 +/- 5.6% and in the 1 microM H2O2 group 6.9 +/- 0.8% (P < 0.05 compared to control). The reduction in infarct size was not present when catalase was added to the hydrogen peroxide-containing solution (26.4 +/- 4.5) or if catalase was present alone (22.9 +/- 1.8% infarction). In conclusion, hydrogen peroxide, 1 microM, protected the heart during reperfusion and reduced the amount of cell death after 120 min of reperfusion. The study demonstrated reduction or delay in infarction based only on treatment in the reperfusion period. The mechanism behind this protection remains to be determined.
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PMID:Hydrogen peroxide as a protective agent during reperfusion. A study in the isolated perfused rabbit heart subjected to regional ischemia. 874 21


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