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

The effects of the calcium antagonists verapamil, gallopamil, nifedipine, felodipine and diltiazem on noradrenaline release during ischemia were studied in isolated perfused rat hearts. Endogenous levels of noradrenaline and its intraneuronal metabolite dihydroxyphenylethyleneglycol (DOPEG) were determined by high pressure liquid chromatography. Global isothermic ischemia of 20 min caused a release of endogenous noradrenaline amounting to 180 +/- 15 pmol/g. The calcium antagonists tested significantly suppressed ischemia-induced noradrenaline release (IC50 in mumols/l: verapamil 1, gallopamil 0.3, nifedipine 1, felodipine 3). Noradrenaline release during ischemia and the inhibitory effect of the calcium antagonists, were independent of extracellular calcium, indicating a nonexocytotic release mechanism. Interaction of the calcium antagonists with the major components of nonexocytotic release, intraneuronal storage and carrier-mediated transport, was tested in normoxic rat hearts. Vesicular storage was not stabilized by the calcium antagonists. In fact, verapamil, gallopamil, diltiazem and felodipine disturbed storage function, as indicated by an increased DOPEG release. Direct interaction with the noradrenaline carrier (uptake1) was demonstrated for verapamil, gallopamil, and diltiazem in a model of 3H-noradrenaline uptake. In conclusion, the calcium antagonists investigated inhibit noradrenaline release in ischemia by a mechanism which is different from blockade of neuronal calcium influx, and is rather due to an interaction with carrier-mediated transport of noradrenaline across the plasma membrane.
J Mol Cell Cardiol 1991 Mar
PMID:Calcium antagonists and cardiac noradrenaline release in ischemia. 188 Aug 12

Accumulation of sodium-ions (Na+) in myocardial cells during both ischemia and calcium (Ca2+)-free perfusion has been suggested to play an important role in the damage occurring during subsequent reperfusion and calcium repletion, respectively. We have used 23Na NMR spectroscopy in combination with shift reagents to determine intracellular Na(+)-concentration [( Na+]i) in isolated rat hearts during either control perfusion followed by ischemia and reperfusion, or during control perfusion, Ca(2+)-free perfusion and subsequent ischemia. [Na+]i during control perfusion was found to be 10.5 +/- 0.6 mmol/l. During 30 min of ischemia [Na+]i rose substantially to 25.0 +/- 3.2 mmol/l. During 15 min of reperfusion [Na+]i initially decreased, but leveled off after approximately 3 min and was 17.9 +/- 3.7 mmol/l at the end of the reperfusion period. Most surprisingly, however, no significant increase of [Na+]i was observed during 30 min of Ca(2+)-free perfusion, although severe calcium paradox damage was shown to occur under the used conditions, when calcium was readmitted to the heart. The absence of a rise of [Na+]i during Ca(2+)-free perfusion was substantiated when during subsequent ischemia a similar rise of [Na+]i was observed as during ischemia without previous Ca(2+)-depletion. We conclude that an increased [Na+]i during Ca(2+)-depletion is not a prerequisite for the calcium paradox to occur, but that increased [Na+]i during ischemia may influence the subsequent reperfusion damage through Na(+)-Ca2+ exchange.
J Mol Cell Cardiol 1991 Mar
PMID:Intracellular sodium during ischemia and calcium-free perfusion: a 23Na NMR study. 188 Aug 14

Radiolabeled deoxyglucose (FDG) has been advocated as a marker of viability of reperfused myocardium during acute infarction. However, data for such recommendation are few. We investigated cardiac deposition of C-14 deoxyglucose (C-14 DG) and of Thallium -201 (Tl-201) in rabbits subjected to coronary occlusion (15, 30, 60 or greater than 100 min) and reperfusion (75 min and 24 h). Measured myocardial concentrations of C-14 DG and Tl-201 in macroautoradiograms were quantitatively correlated in a 24 h reperfusion group with presence of myocardial necrosis evaluated by light microscopy. The major finding in this investigation was that with 30 min or 60 min of ischemia followed by reperfusion there were myocardial regions with significant hypoperfusion (Tl-201) and histologic necrosis. However, in the same myocardial areas, the deposition of C-14 DG was not correlated with the extent of necrosis (r = 0.27). Also, the deposition of C-14 DG in acute myocardial infarction was higher than that of Tl-201 (P = 0.05 by paired T test and by nonparametric Wilcoxon's test). It was also demonstrated that when the occlusion time was varied (15-130 min) and early reperfusion was provided for 75 min or omitted altogether, the myocardial accumulation of Tl-201 was variable and that myocardial sequestration of C-14 DG was higher than perfusion in central and peripheral portions of the area-at-risk. These observations do not support a role for the use of radiolabeled deoxyglucose for the detection of myocardial viability in recently infarcted cardiac muscle.
J Mol Cell Cardiol 1991 May
PMID:Discordance between accumulation of C-14 deoxyglucose and Tl-201 in reperfused myocardium. 188 39

The effects on sarcoplasmic reticulum (SR) Ca2+ transport of solutions mimicking the important intracellular milieu changes associated with short-term hypoxia (hypoxic solutions, as described by Kammermeier et al. J. Mol. Cell. Cardiol. 14: 267, 1982) were examined. SR Ca2+ content was estimated by measuring the magnitude of the caffeine-induced contracture in saponin-skinned rat papillary muscle. SR Ca2+ uptake was inhibited by hypoxic solutions only at loading times less than or equal to 30 s. This inhibition was primarily due to the increase in Pi. The hypoxic solutions had no effect on Ca(2+)-induced Ca2+ release from the SR. We also tested the effects of ATP-free (rigor) solutions that mimic the intracellular environment during late hypoxia and ischemia. Elevating Pi or ADP alone in rigor solution had no effect on SR Ca2+ content. However, elevating Pi and ADP (+/-Mg2+) produced a 44-48% reduction in SR Ca2+ content. This reduction is most likely due to reversal of the SR Ca2+ pump. We conclude that the changes in milieu with short-term hypoxia can depress contractility in intact cardiac muscle by inhibiting SR Ca2+ uptake. During long-term hypoxia or ischemia, these milieu changes can elevate intracellular Ca2+ by reversing the SR Ca2+ pump.
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PMID:Intracellular milieu changes associated with hypoxia impair sarcoplasmic reticulum Ca2+ transport in cardiac muscle. 188 12

Cerebral ischemia and reperfusion results in an active series of metabolic events, eventually leading to cell death. The expression of specific genes during cerebral ischemia and reperfusion may play an important, determinant role in the mechanisms controlling cellular processes. Ten minutes of bilateral carotid occlusion in the Mongolian gerbil was found to increase the messenger RNA for both the c-fos and c-jun protooncogenes. The changes in gene expression were detected in the regions of ischemia, specifically the cortex and striatum, and no increases were seen in either the brain stem or the cerebellum, which possess a separate circulation. Induction of protooncogene mRNA is correlated to the duration of ischemia, i.e., the longer the time of ischemia, the greater the increase in c-fos expression. Pretreatment of animals with pentobarbital reduced the effect of the ischemic insult and prevented the increase in c-fos mRNA. Analysis of the c-fos and c-jun proteins after ischemia demonstrated an increase in the formation of a functional transcriptional complex and association with the AP-1 binding region. These findings suggest that ischemic cell death and recovery in neurodegenerative disorders such as stroke may involve the regulated expression of these protooncogenes early in the pathway of ischemia.
J Mol Neurosci 1991
PMID:Ischemic induction of protooncogene expression in gerbil brain. 190 65

An ideal model of global ischemia in rabbits has not yet been developed. The present study describes a new model of global postischemic reperfusion (GPIR) in the rabbit, characterized by lack of systemic hypotension. The experimental procedure involves reversible occlusion of the bilateral internal carotid arteries (ICA) and bilateral external carotid arteries (ECA) for 60 min combined with permanent ligation of bilateral vertebral arteries (VA). This grouping is called 6-artery occlusion (6AO). Sixty minutes after the occlusion, bilateral ICA and bilateral ECA were released for 120 min at which time the experiment was terminated. The results revealed severely depressed EEG activity; Water content of brain tissue increased to 80.33 +/- 1.20% (control 78.28 +/- 0.59%, p less than 0.01); K, Mg, and Zn decreased (p less than 0.05 or p less than 0.01), and were negatively correlated with tissue water content. Na increased (p less than 0.05) and correlated with water content of brain. No significant changes were observed in lipid peroxide (LPO) levels, but the activity of superoxide dismutase (SOD) of brain tissue decreased (p less than 0.01), and was negatively correlated with water content (r = -0.5808, p less than 0.05). These results were compared with those obtained with the model of 4-artery (bilateral common carotid arteries (CCA) and VA) occlusion (4AO) and suggested that the brain damage be more severe with 6AO than with 4AO.
Mol Chem Neuropathol 1991 Feb
PMID:A new model of global postischemic reperfusion in rabbit. 191 Mar 54

Thirty and 60-min ischemic insults resulted in an increase in free fatty acid and 1,2- diacylglycerol contents of rat forebrain. No significant changes were detected in phospholipids except phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate during ischemic insult. Phosphatidylinositol 4-monohosphate and phosphatidylinositol 4,5-bisphosphate contents decreased during ischemia. Although the increase in free fatty acid contents continued, 1,2-diacylglycerol did not show further increase after 30-min ischemia. These results suggest that there may be another pathway for the accumulation of free fatty acids in addition to phospholipase C coupled to di- and monoacylglycerol lipase. Free fatty acid and 1,2-diacylglycerol contents increased transiently and thereafter decreased to control levels within 90 min after postischemic recirculation. The decrease in arachidonic acid content preceded those of other FFA. Phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate contents gradually increased after the initiation of recirculation in ischemic brains. Lysophosphatidylcholine decreased gradually after temporary increase during 15 and 5-min recirculations in 30 and 60-min ischemic groups. Phospholipase A, phospholipase C, and di- and monoacylglycerol lipase activities did not show significant changes during entire course of recirculation. Total activities of lysophospholipase and acylation enzymes of lysophospholipid demonstrated 1.5-and 2.2-fold increase during 30-min recirculation.
Mol Chem Neuropathol 1991 Feb
PMID:Changes in lipid metabolites and enzymes in rat brain due to ischemia and recirculation. 191 Mar 56

Calpains and calpastatin in the brain of the rabbit were examined in experimental situations that could mimic some features of brain ischemia. Incubations of bisected brains in saline at 39 degrees C for 0.5, 1, or 1.5 h resulted in a decreased calpain I activity in the cytosol and in an increased hydrophobicity of cytosolic calpain II activity. Incubation of brain homogenates at different pH levels demonstrated an almost-complete transfer of calpains from the cytoplasmic compartment to the membranes when pH was lowered from 6 to 5. At pH values lower than 5, the total calpain activity (soluble plus membrane-bound) markedly decreased. No significant changes of calpastatin activity or its subcellular distribution was found following incubation of the homogenates at different pH levels.
Mol Chem Neuropathol 1991 Apr
PMID:Changes in brain calpain activity as a result of in vitro ischemia and pH alterations. 191 Mar 62

The objective of this study was to augment myocardial tissue levels of amphiphiles using a treatment protocol of pantothenic acid, cysteine and dithiothreitol (DTT) in 24 hr fasted pigs and to test their influence on mechanical recovery in reperfusion. Eighteen pig hearts were extracorporeally perfused aerobically, subjected to regionally reversible ischemia in the left anterior descending perfusion system and reperfused. Nine hearts served as a placebo group; nine hearts were treated. All hearts received trace-labeled palmitate to measure fatty acid oxidation and were perfused with an infusion of 20% Intralipid to augment perfusate levels of fatty acids. Fasting alone in the presence of carbon substrates in the coronary perfusate was not sufficient to de-inhibit pantothenic acid kinase such that CoA synthesis was not enhanced. Tissue contents of triacylglycerols and phospholipids in reperfused myocardium were no different than in aerobic heart muscle but free CoA and free and total carnitine were reduced, suggesting a leakage of cytosolic contents across injured sarcolemma. Treatment significantly impaired mechanical recovery during reflow, presumable due to the noxious properties of DTT whose reported effects in heart muscle are wide ranging, difficult to predict in intact hearts and may be harmful.
Mol Cell Biochem 1991 Jun 26
PMID:The effects of pantothenic acid, cysteine and dithiothreitol in intact, reperfused pig hearts. 192 7

The relationship between myocardial cell contracture and injury during total metabolic inhibition (amylobarbital and iodoacetic acid) and ischemia was examined, using 5-50 mM butanedione monoxime (BDM) as an inhibitor of contracture. BDM had no apparent effect on control myocytes during 180 min incubations, but inhibited contracture following anoxia or ischemia in a dose-dependent fashion, as directly quantitated by length/width ratios. Cellular ATP levels decreased at a similar rate in the absence or presence of BDM, following metabolic inhibition. BDM-mediated inhibition of contracture was associated with accelerated cell injury, as defined by: the uptake of an extracellular marker (trypan blue) by the cardiomyocytes, by direct analysis of myoglobin released into the supernatant and by ultrastructural demonstration of defects in sarcolemmal membrane integrity. Calcium was not required for BDM's enhancement of injury, in that cells incubated in calcium free-EGTA buffer showed a similar BDM-mediated acceleration of injury. In the presence or absence of calcium, enhancement of injury was more marked in cells osmotically stressed with a brief incubation in hypotonic buffer, than in cells resuspended in isotonic media. It is concluded that BDM enhances development of osmotic fragility of inhibited or ischemic cardiomyocytes and that contracture is not a necessary contributing factor to myocardial cell death.
J Mol Cell Cardiol 1991 Sep
PMID:Effects of 2,3-butanedione monoxime (BDM) on contracture and injury of isolated rat myocytes following metabolic inhibition and ischemia. 194 93


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