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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present experiments the dominant role in the genesis of arrhythmias of stimulation of beta adrenoceptors over that of alpha adrenoceptors has been demonstrated by: (i) infusion of catecholamines in the isolated right ventricular Purkinje fiber preparation of rabbits; and (ii) by subepicardial microinfusion of these substances to anesthetized thoracotomized dogs. Activation of the latent pacemaker areas by local myocardial ischemia was shown. Catecholamine-induced arrhythmias also resulted from premature excitation of the working myocardium as a consequence of an interaction of Purkinje firing and excitation originating from higher pacemaker areas.
J Mol Cell Cardiol 1986 Apr
PMID:Sympathetic neural mechanisms in cardiac arrhythmias. 371 48

Experiments were performed to determine if xanthine oxidase is a source of free radicals during myocardial ischemia. Open chest dogs were subjected to 1 h of total occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Directly after coronary artery occlusion, Ce141 microspheres were injected into the left atrium to mark the ischemic bed. At the end of reperfusion, the hearts were removed and sectioned. Autoradiography determined the ischemic myocardium at risk, and the necrotic zone was determined by triphenyl-tetrazolium staining. Animals were divided into three groups: control, allopurinol (24-h oral pretreatment 400 mg, then 50 mg/kg IV bolus on occlusion); and superoxide dismutase starting with occlusion (15 000 U/kg). The size of the infarct as a percentage of the tissue at risk was: 23.1 +/- 4.1 for the control; 8.7 +/- 1.2 for the allopurinol group; and 5.4 +/- 1.2 for the superoxide dismutase group. The infarcts in the allopurinol and superoxide dismutase groups were significantly smaller than those in the control groups. In a second series of experiments we determined the xanthine oxidase/xanthine dehydrogenase content of dog myocardium. The left anterior descending branch was ligated for 30 min and then biopsies were removed from both the normal and the ischemic regions. Total enzyme content did not differ between the two regions averaging 0.259 U/g protein for the ischemic tissue and 0.225 U/g protein for the normal region. Only 9.8% of the enzyme was in the oxidase form in the normal region while 32.8% was in the oxidase form in the ischemic zone.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1985 Feb
PMID:Xanthine oxidase as a source of free radical damage in myocardial ischemia. 383 24

Effects of a synthetic, prostaglandin (PGBx) on energy metabolism in isolated, guinea pig hearts were studied using P-31 nuclear magnetic resonance spectroscopy (NMR) or by direct chemical analysis. Polymeric prostaglandin (500 and 750 ng/ml) attenuated the reduction of ATP and adenine nucleotides during 35 min of total transient ischemia. This occurred despite the absence of any significant preischemic changes in heart rate, contractility or coronary vascular resistance. Preischemic perfusion with PGBx extended the time taken to reach 50% reduction in dP/dt following the first few seconds of ischemia. PGBx had no effect on the development of intracellular acidosis during ischemia. Reperfusion resulted in normalization of phosphocreatine but not ATP concentrations in control and experimental groups. Prostaglandin (750 ng/ml) caused faster and more complete recovery of left ventricular dP/dt following reperfusion. In contrast to untreated hearts, dP/dt in PGBx-treated hearts was significantly higher than preischemic values despite incomplete restoration (70% of control) of ATP levels. These results suggest that the beneficial effects of PGBx observed during myocardial ischemia are unrelated to functionally-induced alterations and that PGBx probably has some direct cellular effect on energy metabolism.
J Mol Cell Cardiol 1985 Aug
PMID:A polymeric prostaglandin (PGBx) attenuates adenine nucleotide loss during global ischemia and improves myocardial function during reperfusion. 404 44

Studies in cats suggest alpha-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n = 52), prazosin (1 mg/kg, n = 26), phentolamine (5 mg/kg, n = 18), or phentolamine (same dose) + propranolol (1 mg/kg, n = 10). Alpha-blockade was confirmed by alpha-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation of ischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P less than 0.01), but not by prazosin or phentolamine + propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachycardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective alpha 1-(prazosin), nonselective alpha 1- and alpha 2-(phentolamine), and combined alpha- and beta-blockade (phentolamine + propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model.
J Mol Cell Cardiol 1984 Dec
PMID:Effect of alpha-adrenergic blockade on arrhythmias induced by acute myocardial ischemia and reperfusion in the dog. 615 73

The relationship between functional capillary perfusion patterns and sarcolemmal membrane permeability in localized acute myocardial ischemia was investigated in the rat model. The macromolecule dextran (MW 150,000) labeled with fluorescein (FITC) was intravenously injected. In histological sections, the label fluorescence showed those capillaries which had been perfused by the stained plasma; the blood-tissue barrier could be explored by detection of fluorescein in interstitial spaces and/or within the myocardial cells. Morphological parameters were calculated by semiautomatic image analysis. The data obtained indicate that (1) there is a great heterogeneity in the pattern of capillary perfusion within the reperfused ischemic myocardium; (2) as early as 20 min after coronary artery clamping followed by short reperfusion, the macromolecular tracer can be seen in the cytoplasm of muscle cells randomly distributed in subendocardial areas; (3) only the underperfused areas display permeated myocardial cells. It is suggested that capillary perfusion varies from site to site depending on the difference in cellular membrane permeability changes. The ischemia-induced cell changes can lead to capillary filling defects and an increase in coronary flow resistance. Whether the inadequate blood flow upon reperfusion contributes to further myocyte damage remains a matter of debate.
Exp Mol Pathol 1983 Aug
PMID:Capillary perfusion patterns in reperfused ischemic subendocardial myocardium: experimental study using fluorescent dextran. 619 13

Regional myocardial ischemia was produced in anesthetized dogs by occluding the left branch of the circumflex coronary artery. After 30 or 60 min of occlusion, mitochondria were isolated from both non-ischemic (control) and ischemic transmural samples of the left ventricle and septum. Mitochondria from 60 min ischemic myocardium exhibited a drop in NAD-linked state 3 respiratory rates to 56 +/- 3% of controls and a parallel loss of NADH-CoQ reductase activity to 54 +/- 4% of controls. Analyses of two non-protein components of electron transfer complex I in mitochondria isolated from 60 min ischemic myocardium revealed a decrease in acid-extractable flavin mononucleotide (FMN) to 58 +/- 5% of controls and a small decrease in ubiquinone to 89 +/- 2% of controls. The observed dissociation and apparent washout of non-covalently-bound FMN from the ischemically damaged mitochondria thus accounted nearly quantitatively for the proportionate decrease seen in NADH-CoQ reductase activity and in state 3 respiration with NAD-linked substrates.
J Mol Cell Cardiol 1983 Aug
PMID:Impaired function of mitochondrial electron transfer complex I in canine myocardial ischemia: loss of flavin mononucleotide. 623 81

Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
J Mol Cell Cardiol 1983 Oct
PMID:Production of free radicals and lipid peroxides in early experimental myocardial ischemia. 631 60

Published data regarding the interaction of long-chain acyl CoA derivatives with the protein and phospholipid constituents of biological membranes is reviewed and discussed in relationship to the premise that such interactions may lead to membrane damage during pathological situations. The topics considered include: the detergent properties of long-chain CoA, the interaction with membrane-associated enzymes, biological membranes, or model membrane systems, and the binding to a soluble protein that may facilitate intracellular transport. The effects of long-chain acyl CoA on heart mitochondria and the relevance of such studies to myocardial ischemia also is emphasized.
Mol Cell Biochem 1983
PMID:The interaction of long-chain acyl CoA with membranes. 635 58

We utilized immunoperoxidase methods to study the distribution of CK-B and CK-M in normal, ischemic and necrotic myocardium. Human myocardium was obtained from autopsy (n = 10) and surgery (n = 16). Cardiac tissue from 22 dogs with experimental myocardial infarction induced by closed-chest coronary balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery blood flow for 3 h were studied. Duration of occlusion was 45 min (n = 2), 3 h (n = 8), 5 to 6 h (n = 7), 15 to 24 h (n = 5). Highly purified anti-CK-B and M were prepared in our laboratory and obtained commercially. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for CK-B and CK-M. Necrotic myocardium from patients with acute infarcts (10 to 24 h old) showed markedly reduced immunostaining. In dogs with 3 to 24 h occlusion immunostaining was significantly reduced for both CK-B and CK-M in regions confirmed to be necrotic by triphenyl tetrazolium chloride (TTC) and H & E staining. Myocardial necrosis was confirmed in the 3-h infarcts by electron microscopy (EM). In the four dogs with a 50% reduction in left main flow for 3 h, ischemia was demonstrated by glycogen loss in periodic acid-Schiff stained-sections; but there was no evidence of necrosis by EM or TTC, and there was no loss of immunostaining evident for CK-B and CK-M. Thus, using immunoperoxidase techniques, CK-B and CK-M were visualized in normal and ischemic myocardium, with decreased staining in necrotic tissue. These findings indicate that cell death is necessary for the demonstration of CK-M and CK-B loss from the myocardium by this technique.
J Mol Cell Cardiol 1984 Jan
PMID:Identification and localization of creatine kinase B and M in normal, ischemic and necrotic myocardium. An immunohistochemical study. 636 42

We strongly support the original intriguing hypothesis of Hearse et al. that the oxygen paradox and the calcium paradox are facets of the same problem. We would propose that the major similarity is a final common pathway leading to intracellular calcium overload and the sequelae of the resultant increase in intracellular calcium. In addition, we would propose that the oxygen paradox and ischemic/reperfusion injury are also facets of the same problem with the major similarity being the reintroduction of molecular oxygen to a previously hypoxic myocardium. Finally, we would suggest that the common pathway leading to intracellular calcium overload in the oxygen paradox and ischemic/reperfusion injury and to a lesser extent the calcium paradox involves the generation of oxygen free radicals. The source of oxygen free radical generation in the calcium paradox is perhaps less obvious than in the oxygen paradox. It is proposed that during calcium-free perfusion, calcium is leached from the plasmalemma of the myocyte. There is a resulting increase in membrane fluidity. Within the plasmalemma are a number of calcium sensitive phospholipases. Upon reperfusion with a calcium replete medium, calcium could pool around these membrane bound phospholipases initiating a chain reaction of lipid peroxidation which actually is perpetuated by free radical generation (Equations 5A-5C). Lipid peroxidation opens channels within the plasmalemma rendering a 'leaky' sarcolemma. It is through these channels that calcium could flow down its concentration gradient into the cell. The increased calcium accumulation at the mitochondria would lead to an uncoupling of oxidative phosphorylation. With depleted energy stores, the mitochondria and sarcoplasmic reticulum no longer serve as calcium sinks. This would contribute to the calcium overload seen upon reperfusion. The role of oxygen free radical production would appear to occur during the hypoxic phase of the oxygen paradox and the ischemic phase of ischemic/reperfusion injury and during the reoxygenation/reperfusion phases. With the onset of hypoxia and/or myocardial ischemia there is an increase in reducing equivalents, disturbance and dissociation of intramitochondrial electron transport and release of ubisemiquinone, flavoproteins and superoxide radicals. The increase in reducing equivalents includes NADPH and, in ischemia, catecholamines, hypoxanthine and an increase on xanthine oxidase activity. All of these substrates are capable of participating in free radical production. This increase in free radical production in ischemic tissue is enhanced by acidosis which in the ischemic and hypoxic myocardium approaches pH 6.0-6.4.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1984 Nov
PMID:Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury. 639 65


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