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

It is a characteristic feature of the myocardium that the derangement in function [6] and the depletion of the ATP pool [1, 2, 9] that occur subsequent to oxygen deficiency persist when blood flow is restored. Of renewed interest is the inability of the heart to replenish rapidly its adenine nucleotide pool once it has been diminished during a brief period of regional ischemia [2, 9]. A hypothesis that could explain this metabolic insufficiency of the myocardium is that the biosynthesis of adenine nucleotides is very slow in the normal heart and is increased only moderately during postischemic recovery [15] so that the replenishment of adenine nucleotides is not affected appreciably. To substantiate such a hypothesis it is necessary to provide evidence that the restitution of the ATP pool can be accelerated by stimulation of this biosynthetic process. In previous studies ribose has been recognized as a substrate that enhances markedly adenine nucleotide biosynthesis in the rat heart [11, 12]. We now demonstrate that continuous i.v. infusion of ribose during recovery from a 15-min period of myocardial ischemia in rats leads to restoration of the cardiac ATP pool within 12 h, whereas 72 h are needed for ATP normalization without any intervention.
J Mol Cell Cardiol 1984 Sep
PMID:Ribose accelerates the repletion of the ATP pool during recovery from reversible ischemia of the rat myocardium. 643 98

Myocardial ischaemia, whether produced by coronary artery ligation or by hypoxic low-flow perfusion of the isolated rat heart, has been shown to be associated with a significant depression in mitochondrial function, as well as an increase in tissue free fatty acid (FFA) levels. Although the effects of FFA on mitochondrial oxidative phosphorylation function in vitro are well established, it has not yet been shown that increased tissue FFA levels are causing the depression in mitochondrial function in ischaemia. Using the isolated perfused rat heart, several experiments were performed to gain more information regarding (i) the validity of the Dole FFA extraction technique; (ii) controlling factors; (iii) the relationship between tissue FFA and mitochondrial function and (iv) sources of tissue FFA in ischaemia. Significant elevation of tissue FFA was achieved by perfusion with (i) substrate-free Ringer and (ii) phosphatidylcholine. Elevation of tissue FFA obtained by perfusing with long-chain fatty acids was due to extracellular accumulation. Reduction of tissue FFA levels was observed by perfusing with (i) albumin, (ii) glucose, insulin and propranolol. Our results also suggest that lysosomal involvement could cause the increase in tissue FFA levels in myocardial ischaemia.
J Mol Cell Cardiol 1984 Aug
PMID:Myocardial tissue free fatty acids. 648 13

Oxygen free radicals and their metabolites generated from activated neutrophils have been implicated in mediating the cardiovascular dysfunction of such diverse etiologies as myocardial ischemia and reperfusion injury, Gram negative sepsis, myocarditis and acute cardiac allograft rejection, but a direct demonstration of neutrophil derived oxygen free radical mediation of cardiovascular dysfunction has not been accomplished. In this study, we have demonstrated that activation of the canine neutrophil system, in vivo, results in the generation of oxygen free radicals that are capable of disrupting cardiovascular function producing a significant decrease in mean arterial pressure and cardiac index without any significant effect on the conduction system of the myocardium. Neutrophil depletion or pretreatment with superoxide dismutase and catalase inhibited the effects of activated neutrophils. This study provides evidence that neutrophil-derived reduced oxygen intermediates are able to induce severe cardiovascular dysfunction.
J Mol Cell Cardiol 1984 Nov
PMID:Neutrophil-derived, oxygen free radical-mediated cardiovascular dysfunction. 652 Aug 76

To examine some of the characteristics of the local noradrenaline (NA) release in myocardial ischemia a study was made on Langendorff-perfused rat hearts, prelabelled with 3H-NA. The left coronary artery was ligated for 15, 30, 60 or 120 min, followed by 10 min of reperfusion. The coronary effluent was collected and analyzed for radioactivity to indicate release of 3H-NA. In some of the experiments the fraction of 3H-NA was determined. As substrate in the perfusion medium either glucose (11.1 mM) or sodium lactate (5.0 mM) was used. During the ischemic period there was a slight decrease in the outflow of radioactivity. However, reperfusion was associated with a rapid and marked outflow of radioactivity, including an increased fraction of 3H-NA, in the effluent. Compared to glucose as perfusion substrate, lactate caused a significantly higher (P less than 0.01) outflow of tritiated substances after 60 and 120 min of regional ischemia. With lactate there was an almost linear relationship between reperfusion efflux of 3H and duration of ischemia. With glucose, the reperfusion outflow increased less rapidly after a duration of ischemia longer than 15 min. It is concluded that the degree of local NA release in myocardial ischemia depends on both the duration of the ischemic period and the substrate used. Glucose attenuates the reperfusion outflow of NA, especially after longer periods of ischemia. The effect may be due to decreased myocardial cell damage with this substrate and/or a direct protection of the adrenergic nerve endings.
J Mol Cell Cardiol 1983 Dec
PMID:Ischemia-induced noradrenaline release in the isolated rat heart: influence of perfusion substrate and duration of ischemia. 666 30

In acute reversible myocardial ischemia extracellular potassium activity rises 4 to 5 fold within 10 to 15 min after interruption of coronary perfusion. The underlying net cellular K+ loss is likely to be caused by an increased K+ efflux in the presence of maintained Na+/K+ pumping (i.e. active K+ influx). A hypothesis is discussed which relates increased K+ efflux to the formation of weak acids in the cells during anaerobic metabolism. However, the exact mechanism remains to be determined by further experimental investigations.
J Mol Cell Cardiol 1984 May
PMID:Extracellular potassium accumulation in acute myocardial ischemia. 673 81

Myocardial protection during open heart surgery is achieved by general cooling and cold cardioplegia. However sympathetic activation during the operation causes raised circulating catecholamine levels that might negatively influence the myocardial metabolism. Moreover, local liberation of catecholamines, in "poorly perfused' regions of the myocardium in patients with ischemic heart disease, might occur. In respect of these problems, we studied the influence of noradrenaline at different temperatures on the isolated perfused rat heart. The temperatures chosen were: 10, 20, 32, 37 and 39 degrees C. The results show clearcut adverse effect of noradrenaline at 32 degrees and higher, on metabolism and hemodynamic performance. At lower temperatures there still seem to be an adverse effect of noradrenaline although not statistically significant. The results of this study indicates the importance of presurgical myocardial protection especially of badly perfused myocardial areas. Such protection could be accomplished by beta-blockade and/or loading of the myocardium with glycogen by glucose-insulin-potassium infusion.
J Mol Cell Cardiol 1983 Apr
PMID:Influence of noradrenaline and temperature on the isolated perfused rat heart. 687 80

Scanning electron microscopy and transmission electron microscopy were used together with tannic acid and ruthenium-red staining to examine connective tissue damage caused by acute myocardial ischemia for 20, 40 and 120 min in pig hearts. The microsphere blood flow technique revealed that blood flow was approximately 0.02 ml/min/g in inner, middle and outer thirds of the ischemic zone. After 20 min of occlusion of the left anterior descending coronary artery, the collagen network and microfilaments became irregularly arranged. After 40 min of occlusion, ruthenium-red positive glycoprotein material around the collagen fibrils and elastin began to disappear. After 2 h occlusion, the collagen fibrils and microfilaments had separated from the basement membrane. Collagen fibrils, elastic fibers, and microfilaments were broken down and were found in decreased quantities. These results have revealed that the connective tissue remains intact during the first 20 min of coronary occlusion despite zero blood flow and mild cellular changes but does undergo prominent alterations after 40 min of occlusion.
J Mol Cell Cardiol 1983 Apr
PMID:Connective tissue changes in early ischemia of porcine myocardium: an ultrastructural study. 687 83

The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.
J Mol Cell Cardiol 1983 Jun
PMID:Effects of ischemia and reperfusion on pyruvate dehydrogenase activity in isolated rat hearts. 687 85

Species-related differences in the mechanisms of noradrenaline release during normoxia and myocardial ischemia emphasize the need for studies on human hearts. Therefore, the mechanisms of noradrenaline release were investigated during normoxia and energy depletion in incubated human atrial tissue and compared to the release characteristics in normoxic and ischemic rat heart. Potential differences of atrial versus ventricular myocardium were assessed by comparing catecholamine release during electrical stimulation and ischemia in isolated rat atrium with release characteristics in the intact perfused heart. The overflow of endogenous noradrenaline and its deaminated metabolite dihydroxyphenylethyleneglycol (DOPEG) were determined by high pressure liquid chromatography and electrochemical detection. During normoxia noradrenaline release was evoked by electrical field stimulation. Stimulation-induced noradrenaline release depended on the extracellular calcium concentration in both species and was almost completely suppressed under calcium-free conditions. The release was significantly inhibited by neuronal (N-type) calcium channel blockers such as omega-conotoxin (100 nmol/l) and cadmium chloride (100 mumol/l), indicating a predominant role of N-type calcium channels in exocytotic noradrenaline release from sympathetic neurons in human and rat heart. Desipramine (100 nmol/l) enhanced the overflow of noradrenaline evoked by electrical stimulation in both species by blocking neuronal catecholamine uptake (uptake1). Myocardial ischemia was caused by interruption of perfusion flow in rat heart and simulated by anoxic and glucose-free incubation in human and rat atrial tissue. Ischemia- and anoxia-induced noradrenaline release in rat heart and human atrial tissue was unaffected by varying extracellular calcium concentrations and occurred even after omission of calcium and addition of EGTA (1 mmol/l). In both species neither omega-conotoxin (100 nmol/l) nor cadmium chloride (100 mumol/l) affected ischemia-induced noradrenaline overflow in both rat heart and atrium as well as in human atrium. In human and rat atrial tissue, blockade of energy metabolism in the presence of oxygen (cyanide model) resulted in a desipramine-sensitive release of noradrenaline, which was accompanied by DOPEG overflow, indicating increased axoplasmic noradrenaline concentration. The data imply a dual mechanism of noradrenaline release in the human heart. During normoxia noradrenaline release is modulated by neuronal calcium influx indicating exocytotic release. Ischemia-induced noradrenaline release, however, is independent of calcium and inhibited by uptake1 blockade suggesting nonexocytotic release mechanism. The characteristics of noradrenaline release in human atrial tissue provide evidence for carrier-mediated release of noradrenaline from sympathetic neurons operative in the ischemic human myocardium.
J Mol Cell Cardiol 1995 May
PMID:Two different mechanisms of noradrenaline release during normoxia and simulated ischemia in human cardiac tissue. 747 74

Although it is well known that myocardial ischemia induces the depletion of myocardial ATP and sustained myocardial dysfunction, the mechanisms causing impaired myocardial function have not been elucidated completely. To clarify the relationship between ATP depletion and myocardial contractility, we investigated the influence of myocardial ATP depletion on spontaneous beating in cultured rat ventricular myocytes. Furthermore, because catecholamines have been used to improve myocardial contraction in the ischemic heart, we attempted to determine whether the ATP depletion per se alters the contractile responses to alpha 1- and beta-adrenoceptor stimulation. After 24 hr of culture in the presence of a metabolic inhibitor, 2-deoxyglucose (2DG, 5mM), myocardial contractility decreased to 19% of the vehicle level, and returned to normal after the removal of 2DG. The beating rate did not show any alterations in the vehicle, in the presence of 2DG (2DG [+/+]) or after the removal of 2DG (2DG [+/-]). Norepinephrine (NE) caused significant decreases in beating rate and increases in contractility in all groups. Isoproterenol (ISP) caused significant increases in beating rate and contractility in all groups. In the 2DG (+/+) group, the contractility was significantly lower as compared to other groups during NE or ISP stimulation. However, the percent change of contractility was similar to those of other groups after NE or ISP stimulation in the 2DG (+/+) group. These results suggest that decreased myocardial ATP causes the decreased contractility and does not affect the alpha 1- or beta-adrenoceptor-mediated responses.
Res Commun Mol Pathol Pharmacol 1995 Jul
PMID:Effects of 2-deoxyglucose, a metabolic inhibitor, on spontaneous contraction and adrenoceptor responsiveness in cultured rat ventricular myocytes. 758 56


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