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

Calcium entry blockers seem useful for energy conservation in the ischemic heart. Their exact mechanism of action, however, remains uncertain. In this study we investigated the effect of 30 nM nisoldipine on carbohydrate metabolism in isolated rat heart perfused with glucose-containing medium. Nisoldipine increased flow 1.5-fold and reduced apex displacement 60%. We induced ischemia by lowering the perfusion pressure from 72 to 14 mm Hg, which resulted in a flow reduction in untreated hearts by 80%. Lactate production rose 16-fold, glucose utilization increased fourfold, and the heart glycogen content decreased by 32%. Nisoldipine treatment diminished ischemic lactate release by 77%. It decreased glucose utilization to normoxic levels and reduced glycogen breakdown to a value intermediate to the ischemic and normoxic ones. We conclude that nisoldipine reduces glycolysis in the ischemic heart. Consequently, it appears that the ATP-saving effect of nisoldipine during ischemia, reported elsewhere, is due to a lower energy demand rather than increased ATP production.
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PMID:Reduced glycolysis by nisoldipine treatment of ischemic heart. 241 Jun 80

The reflex responses to static contraction are augmented by ischemia. The metabolic "error signals" that are responsible for these observed responses are unknown. Therefore this study was designed to test the hypothesis that static contraction-induced pressor responses, which are enhanced during muscle ischemia, are the result of alterations in muscle oxygenation, acid-base balance, and K+. Thus, in 36 cats, the pressor response, active muscle blood flow, and muscle venous pH, PCO2, PO2, lactate, and K+ were compared during light and intense static contractions with and without arterial occlusion. During light contraction (15-16% of maximal), active muscle blood flow increased without and decreased with arterial occlusion (+35 +/- 12 vs. -60 +/- 11%). Arterial occlusion augmented these pressor responses by 132 +/- 25%. Without arterial occlusion, changes (P less than 0.05) were seen in PO2, O2 content, PCO2, and K+. Lactate and pH were unchanged. With arterial occlusion, changes in muscle PCO2 were augmented and significant changes were seen in pH and lactate. During intense static contraction (67-69% of maximal), muscle blood flow decreased without arterial occlusion (-39 +/- 9%) and decreased further during occlusion (-81 +/- 6%). Arterial occlusion augmented the pressor responses by 39 +/- 12%. All metabolic variables increased during contraction without arterial occlusion, but occlusion failed to augment any of these changes. These data suggest that light static ischemic contractions cause increases in muscle PCO2 and lactate and decreases in pH that may signal compensatory reflex-induced changes in arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potentiation of the exercise pressor reflex by muscle ischemia. 249 81

Arginine8-vasopressin (AVP) causes hindlimb paralysis, loss of nociceptive responsiveness and increased arterial pressure after spinal subarachnoid injection in rats. In these experiments, the effects of paralytic intrathecal doses of AVP on rat brain and spinal cord blood flow, vascular resistance and cardiac output were measured using radiolabeled microspheres. Ten minutes after injection, AVP (10-100 pmol) elevated mean arterial pressures significantly, increased vascular resistances in thoracic and lumbosacral spinal cord and reduced blood flow to the lumbosacral spinal cord without altering cardiac output, total peripheral resistance and blood flow to brain and other spinal cord regions. Lumbosacral blood flows remained significantly reduced 30 min after injection of 100 pmol of AVP, and recovered to pretreatment base-line levels by 60 min postinjection. Lactic acid concentrations were elevated significantly in spinal cerebrospinal fluid samples removed 5 to 15 min after AVP injection (100 pmol). The selective AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arg8-vasopressin, which previously blocked the effects of AVP on hindlimb motor and nociceptive function, in these experiments also blocked the AVP-induced increases in arterial pressure and reductions in lumbosacral perfusion. Intravenous infusion of the vasodilators papaverine and nifedipine failed to block AVP-induced hindlimb paralysis. Nifedipine, however, did accelerate subsequent recovery of hindlimb motor function, although it did not alter the lumbosacral blood flow reductions measured at 10 and 30 min after AVP injection. These findings indicate that AVP has significant vascular effects in the rat spinal cord that are associated with ischemia and neurological dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginine8-vasopressin reduces spinal cord blood flow after spinal subarachnoid injection in rats. 252 87

Skeletal muscle contraction and metabolism was evaluated using an in vivo, intact autoperfused canine hindlimb model during 7 hours of reperfusion following 4 hours of complete ischemia, with and without bolus administration of superoxide dismutase (SOD) and catalase (CAT) at the start of reperfusion. Contractile tension of paw dorsiflexion during reperfusion demonstrated small but statistically non-significant increases of recovery towards pre-ischemic baseline with SOD/CAT (i.e. 43% +/- 10 vs 32% +/- 9 with muscle-stimulated tetanic tension). Oxygen utilization by the hindlimb rose during reperfusion from a baseline in the control group of 2.4 +/- 0.3 ml 02/min to 5.4 +/- 1.1 during the first 10 minutes and plateaued at 3.5 +/- 1.3 by the first hour with no differences in the SOD/CAT group. Lactate clearance was prompt (increase from a pre-ischemia value of zero to 0.93 +/- .14 mM/min by 5 minutes and return to near-zero by 1 hour in controls) exhibiting no sustained anaerobic metabolism and was not affected by SOD/CAT. These finding demonstrate irreversible loss of 60-70% of skeletal muscle contraction with preservation of aerobic metabolic capacity at 225% of basal activity. Bolus administration of SOD/CAT at the start of reperfusion offered no significant improvement in metabolic or contractile function. These observations, in a model simulating the in vivo setting, necessitate evaluating alternate ischemia reperfusion conditions and modified free-radical inhibitor protocols before any clinical benefit can be assumed.
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PMID:Contractile and metabolic function following an ischemia-reperfusion injury in skeletal muscle: influence of oxygen free radical scavengers. 263 48

For the validation of volume-selective 1H and 31P NMR spectroscopy of the brain methods are required that allow high resolution quantitative mapping of tissue pH and metabolites on intact brain slices. The following techniques are proposed for this purpose. Tissue pH is imaged on cryostat sections of in situ frozen brains, using umbelliferone as a fluorescent pH indicator (Csiba et al, Brain Res 289, 334-337 (1983]. Regional tissue ATP content is measured in adjacent cryostat sections, using the luciferine/luciferase system of fireflies for evoking substrate-specific bioluminescence (Kogure and Furones Alonso, Brain Res. 154, 273-284 (1978]. Lactate content is imaged in a similar way by inducing substrate-specific bioluminescence with lactate dehydrogenase and luciferase from vibrio Fischeri (Paschen, J. Cereb. Blood Flow Metab. 5, 609-612 (1985]. The spatial resolution of these techniques is better than 100 mu, as exemplified in experimental brain tumors and brain infarct of cats. The applicability of biochemical mapping for the validation of NMR spectroscopy was tested in a global brain ischemia model of cat by correlating surface coil 31P and 1H spectra with the corresponding regional biochemical data, measured in the sensitive volume of the coil. Correlation coefficients were r = 0.907, 0.852 and 0.924 for pH, lactate and ATP, respectively. These results demonstrate that the biochemical measurements obtained by bioluminescence and fluoroscopic imaging correlate closely with the NMR data and, therefore, are appropriate for the validation of more complex applications, such as volume-selective spectroscopy of brain infarcts or tumors.
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PMID:Imaging of brain tissue pH and metabolites. A new approach for the validation of volume-selective NMR spectroscopy. 270 7

The effect of inhibition of glycolysis with sodium iodoacetate (IAA) on the changes induced by total ischemia was studied in canine left ventricle. Hearts were excised from phenobarbital anesthetized dogs and the circumflex (LCC) and anterior descending (LAD) branches of the left coronary artery were perfused in order to expose the LCC region to 48 mumol of IAA (about 1.5 mumol/g wet wt). The LAD regions of the same hearts served as untreated control myocardium. Hearts then were subjected to total ischemia in vitro at 37 degrees C. Metabolites, ultrastructure, and the capacity of thin incubated slices of heart to maintain volume and ion gradients were studied in the control and IAA-treated regions. Depletion of ATP to levels of 3-4% of control occurred in only 4-5 min of ischemia in the IAA-treated myocardium, but similar depletion required 90 min of total ischemia in untreated myocardium. These low levels of ATP were associated with marked contracture-rigor. Depletion of ATP in the IAA treated region was accompanied by a marked increase in adenosine levels in the tissue at the onset of rigor (approximately 5 min); at this time, as much as 50% of the adenine nucleotide pool (sigma Ad) was in the form of adenosine. In contrast, inosine was the predominant catabolite at 5 min in control myocardium, and only composed 16% of the sigma Ad pool. Thus, pretreatment with IAA produced an enormous acceleration in the rate at which the sigma Ad pool was consumed in totally ischemic myocardium. Lactate, the principal glycolytic intermediate which accumulates in totally ischemic tissue, was not formed in the IAA-treated heart. Moreover, IAA treatment did not accelerate the rate at which ultrastructural evidence of lethal injury developed in the poisoned myocytes. Thus, in a setting in which lactate accumulation did not occur, totally ischemic myocytes tolerated a very low level of high energy phosphate for a longer period of time than did untreated tissue before ultrastructural signs of cell death developed. The results indicate that marked ATP depletion, pe se, does not necessarily cause prompt sarcolemmal disruption.
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PMID:Total ischemia III: Effect of inhibition of anaerobic glycolysis. 273 29

Ischemic dysfunction, including contracture, has been attributed to lack of ATP, although previous work has not been consistent with this concept. We describe here a model of no flow ischemic arrest, characterized by depressed levels of mechanical function upon reperfusion and high energy phosphate stores within normal limits. The decreased mechanical function bears an inverse relationship to myocardial lactate levels after twenty-minutes of reperfusion in the absence or presence of dichloroacetic acid (DCA). Post-ischemic non-DCA treated hearts attained peak work of only 25% of that of controls, while those treated with DCA following ischemia performed almost as well as controls. ATP and CP levels remained high in both DCA treated and non-DCA treated hearts. Lactate levels were high in hearts immediately following ischemia, but were reduced to control levels in post-ischemic hearts perfused with DCA within twenty minutes, whereas those not treated with DCA had lactate levels two to three times that of controls within the same time period. Pyruvate dehydrogenase (PDH) activity was reduced in non-DCA treated post ischemic hearts after twenty minutes reperfusion but was elevated above controls in hearts reperfused with DCA. The data indicates that DCA increases mechanical performance of the isolated post-ischemic rat heart and the proposed mechanism for this increase is the oxidative removal of lactate resulting from an increase in PDH activity.
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PMID:The effect of dichloroacetate on the isolated no flow arrested rat heart. 274 13

Cerebral metabolism was investigated in cerebral ischemia in fasted Mongolian gerbils by in vivo magnetic resonance spectroscopy (MRS). Ischemia was induced by bilateral carotid artery occlusion and continued for 30 min. Recovery was achieved by releasing the occlusion. High energy adenylates, free phosphates as well as intracellular pH were measured by 31P-MRS. Cerebral lactate levels were determined by 1H-MRS. Furthermore, extracellular sodium levels were monitored by 23Na-MRS. The results showed that intracellular pH decreased to pH = 6.601 at 7.5-15 min after carotid ligation and was regulated back to pH = 6.670 during ischemia. pH returned to preischemic levels 45 min after ischemia and there was an overshoot (pH = 7.241) in pH levels at 67.5-75 min after recirculation. The accumulation of lactate was slower and the accumulation continued after intracellular pH started to regulate back to normal levels. Lactate decreased following recirculation, but was still higher than the preischemic level at 90 min after recirculation. The results show that changes in intracellular pH is not parallel those in lactate levels, suggesting a different mechanism for regulating intracellular pH. The signal intensity of sodium was dropped before ATP disappeared, and rapidly normalized at 14-26 min after recirculation, at which time ATP had also normalized. This result suggests that the loss of signal intensity of 23Na shows depolarization induced by ischemia and Na-K ATP pump failure.
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PMID:[Studies of metabolic changes during and following cerebral ischemia in gerbils by in vivo multi nuclear magnetic resonance spectroscopy]. 280 45

To determine the buffering capacity of ischemic rat myocardium, lactate production was altered by glycogen depletion prior to total global ischemia. Lactate production was monitored by 1H-NMR spectroscopy in perfused rat hearts and determined by enzymatic assay of freeze-clamped tissue extracts. Intracellular pH was measured by 31P-NMR spectroscopy. The relationship between total lactate produced and pH varied considerably, depending on the final pH reached. At pH greater than 6.4 this relationship is linear with a total buffering capacity (delta lactate/delta pH) of 25 mumol H+/g wet weight per pH unit. At lower pH values (pH less than 6.4), the total buffering capacity increases progressively. Since ischemia is invariably accompanied by ATP and phosphocreatine (PCr) hydrolysis, the proton production/consumption during high-energy phosphate hydrolysis must be considered when evaluating the intrinsic buffering capacity of the myocardium against proton loads produced by lactate production from glucose and glycogen. Schemes are presented which allow an estimation of the contribution of ATP and PCr hydrolysis and the buffering by the CO2/HCO3- system during ischemia. At pH greater than 6.4, the majority (about 60%) of buffering is due to hydrolysis of adenosine triphosphate, phosphocreatine in the heart, and neutralization of sodium bicarbonate in the perfusate. At pH less than 6.4 an increasing proportion of cardiac buffering is from intrinsic cardiac buffers, most likely from intracellular proteins. After correction for these contributions to the observed total cardiac buffering capacity, the intrinsic buffering capacity of the myocardium can be accounted for by a high capacity (170 mumol/g wet weight) but low pKa (5.2) buffering system.
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PMID:Determination of buffering capacity of rat myocardium during ischemia. 284 84

Marker enzyme activities of different subcellular fractions were analyzed in cortex homogenates from rat kidney after different periods (15, 30, 60, and 90 min) of warm ischemia. Lactate dehydrogenase, alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and succinate-cytochrome c reductase were not altered by ischemia in these periods. ATPase (2,4-dinitrophenol-stimulated and azide-sensitive), 5'-nucleotidase, K-Mg-nitrophenylphosphatase decline within 30 min of ischemia, whereas the microsomal enzymes glucose-6-phosphatase and NADPH-cytochrome c reductase decreased not before 60 min of ischemia. The early decrease of ATPase and of plasma membrane enzymes can be regarded as a consequence of membrane alterations. This enzymatic approach may be helpful to evaluate pharmacological agents for preventing and reserving ischemic effects in kidneys in a rational manner.
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PMID:Changed enzyme activities in rat kidney during ischemia. 286 6


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