Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphorus-31 magnetic resonance (31P MR) spectroscopy was used to obtain serial in vivo measurements of cerebral adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH levels in rats during temporary global cerebral ischemia and reperfusion. Three groups of 4 rats each that recovered from permanent bilateral vertebral artery occlusion were placed in a MR spectrometer and subjected to remotely controlled bilateral carotid artery occlusion lasting 6, 15, or 30 minutes followed by 1 hour of reperfusion. Four additional rats that developed systemic hypotension (2 during a 6-minute occlusion and 2 during a 15-minute occlusion) were also studied. 31P MR spectra were obtained in each rat before, during, and after ischemia. Rats in which MR spectra showed metabolic recovery underwent a second occlusion followed by reperfusion and sacrifice. In the 12 normotensive rats, metabolic alterations began within 3 minutes after the onset of global ischemia. By the end of the occlusion period, cerebral ATP had decreased by 20 to 100% in 10 rats and PCr had decreased by 15 to 75% in all 12; Pi increased by 25 to 240%. The mean intracellular pH decreased from 7.33 to 6.9 +/- 0.6. The degree of metabolic deterioration during ischemia was not related to the duration of occlusion. During reperfusion, ATP, PCr, Pi, and intracellular pH returned to normal in 4 rats; 5 rats had partial metabolic recovery, and 3 had minimal or transient metabolic recovery followed by progressive deterioration. All rats that developed systemic hypotension had a decrease in ATP, PCr, and intracellular pH and an increase in Pi during the initial occlusion. Each had transient partial recovery in ATP during reperfusion, and 2 had slight recovery of PCr. The onset of hypotension was followed by depletion of these metabolites, progressive increase in Pi, and progressive intracellular acidosis. All rats that deteriorated metabolically after reversal of carotid occlusion died by the end of the reperfusion period or soon after. The 8 rats that recovered from the first occlusion were subjected to a second period of ischemia, during which each rat showed severe depletion of metabolites. During the second reperfusion, only 1 rat showed significant metabolic recovery, which lasted only 30 minutes and was followed by progressive deterioration. Severe global cerebral ischemia was associated with a progressive decline in both ATP and PCr, whereas less complete ischemia seemed to be characterized by stabilization or recovery of ATP and continued depression of PCr.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sequential in vivo measurement of cerebral intracellular metabolites with phosphorus-31 magnetic resonance spectroscopy during global cerebral ischemia and reperfusion in rats. 369 5

Phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) was used to assess the temporal changes of high-energy phosphate metabolites in the region of acute myocardial ischemia of open-chest cats. Eight anesthetized cats were studied following ligation of the left anterior descending coronary artery. Creatine phosphate showed a 79 +/- 16% (mean +/- SD) reduction by 4 min after the onset of ischemia. Prominent qualitative reductions of the spectral peak of creatine phosphate occurred by 40 s after ischemia. Adenosine triphosphate measured under the beta spectral peak (beta-ATP) decreased 37 +/- 9% by 20-25 min after ligation of the left anterior descending coronary artery. These reductions developed more slowly and were of smaller magnitude than those of creatine phosphate. Intracellular pH decreased from 7.39 +/- 0.07 to 7.13 +/- 0.09 units by 40 s after ischemia. By 30 min, pH decreased to 6.07 +/- 0.40 units. The study shows, therefore, the temporal changes of high-energy phosphate metabolites during ischemia in localized regions of the myocardium of open-chest animals.
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PMID:In vivo evaluation of intracellular pH and high-energy phosphate metabolites during regional myocardial ischemia in cats using 31P nuclear magnetic resonance. 371 90

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control (10 min), normoxic cardioplegia (10 min), intermittent global ischemic arrest (two 15-min periods separated by 2 min infusion of the normoxic cardioplegic perfusate), and normoxic postischemic control reperfusion (60 min). Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl2, and 20 mM MgCl2 with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of 31P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P less than 0.01) that persisted throughout the first 50 min of postischemic reperfusion. Diltiazem in combination with magnesium cardioplegia was detrimental to postischemic functional recovery, despite a rapid restoration of high-energy phosphate stores. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically. The mechanistic basis and drug specificity of this response require further clarification. The present findings appear to exclude ATP and PCr production, and structural causes as the basis for the observed aberrant functional recovery from global ischemia of magnesium plus diltiazem-arrested hearts.
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PMID:Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia. 371 20

In this study, the tolerance of skeletal muscle to tourniquet application (ischemia) and to acute compartment syndrome (ischemia and pressure) was compared. In five animals, the cuff of a pneumatic tourniquet was inflated to 350 millimeters of mercury at the level of the thigh for three hours. In five other animals, an acute experimental compartment syndrome was created in one anterolateral compartment by autologous plasma infusion. The compartment pressure (measured by wick catheter) was maintained at a level equal to the mean arterial pressure for three hours. At three hours, reperfusion was established in both groups, either by tourniquet release or by decompressive fasciotomy and epimysiotomy. During both the ischemic period and a two-hour recovery period immediately thereafter, the mean intracellular pH and high-energy phosphate profile (levels of adenosine triphosphate and phosphocreatine) of the muscles of the anterolateral compartment were monitored non-invasively by phosphorus nuclear magnetic-resonance spectroscopy. Muscle biopsies were done the following day to take specimens for electron microscopic analysis of ultrastructural cellular degeneration. During ischemia, the cellular levels of phosphocreatine decreased at an identical rate in both groups. In contrast, the levels of adenosine triphosphate diminished rapidly in the animals with the compartment syndrome, but remained unchanged in the tourniquet group. Ischemic muscle acidosis was more severe in dogs with the compartment syndrome. In the tourniquet group, the phosphocreatine, adenosine triphosphate, and pH were all normal within fifteen minutes after release of the tourniquet, but these values remained depressed even two hours after fasciotomy in the group with compartment syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparative study of the tolerance of skeletal muscle to ischemia. Tourniquet application compared with acute compartment syndrome. 373 72

Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C. 377 91

Changes in diastolic chamber distensibility (DCD) during hypoxemia and ischemia were studied in isolated-buffer-perfused rabbit hearts. Two minutes of hypoxemia (low PO2 coronary flow) resulted in a shift of the diastolic pressure-volume curve to the left, i.e., distensibility was decreased (hypoxemic contracture). In contrast, 2 minutes of ischemia (zero coronary flow) resulted in an initial shift of the diastolic pressure-volume curve to the right indicating increased distensibility, which was followed by a later (30 minutes) shift to the left (ischemic contracture). Two minutes of ischemia superimposed on hypoxemia caused complete reversal of contracture. A quick stretch and release applied to the myocardium reversed late ischemic contracture but did not effect early hypoxemic contracture. The role of intracellular pH in modulating changes in DCD during hypoxia and ischemia was studied using phosphorus-31 nuclear magnetic resonance spectroscopy of isolated-buffer-perfused rat hearts that demonstrated changes in DCD similar to rabbit hearts during hypoxemia and ischemia. Intracellular pH decreased from 7.03 +/- 0.02 to 6.87 +/- 0.03 (p less than .01) during 2 minutes of ischemia but did not change significantly during 4 minutes of hypoxemia. When 2 minutes of ischemia were superimposed on hypoxemia, pH decreased from 6.99 +/- 0.01 during hypoxemia to 6.88 +/- 0.02 after 2 minutes of ischemia (p less than .01), concomitant with the complete reversal of hypoxemic contracture. These results suggest different mechanisms for late ischemic and early hypoxemic contracture and also suggest an explanation for the opposite initial changes in DCD seen after brief periods of ischemia and hypoxemia. The early development of contracture during hypoxemia and rapid redevelopment of diastolic tension after quick stretching are consistent with the hypothesis that hypoxemic contracture results from persistent Ca++-activated diastolic tension secondary to impaired calcium resequestration by the sarcoplasmic reticulum. In contrast, the late development of contracture during global ischemia and reversal by quick stretching is compatible with rigor bond formation. The initial increase in distensibility during early ischemia and the reversal of hypoxemic contracture by a brief period of superimposed ischemia probably is the result of two factors present during ischemia but not during hypoxemia: the collapse of the coronary vasculature and loss of the "erectile" effect and, the rapid development of intracellular acidosis, which has been shown to affect myofibrillar calcium sensitivity, and this may lead to a decrease in Ca++ activated diastolic tension.
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PMID:Acute alterations in diastolic left ventricular chamber distensibility: mechanistic differences between hypoxemia and ischemia in isolated perfused rabbit and rat hearts. 380 27

To evaluate the reliability of phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of acute testicular ischemia, vascular integrity, and spermatogenesis, the authors studied in vivo canine and primate testicles grouped as follows: group 1 testes (n = 8), in situ canine controls; group 2 (n = 11), canine testes subjected to warm ischemia; group 3, canine (n = 4) and primate (n = 4) testicles from hormone-treated animals. Group 1 control testicles showed high monophosphoester (MP) levels; low levels of inorganic phosphate (Pi), phosphodiester (PD), and phosphocreatine; and high levels of adenosine triphosphate (ATP). Group 2 testes revealed a time-dependent decay of MP/Pi ratios (from 2.1 to 0.70). Regeneration of ATP was noted in the acute reperfusion period. After 6 weeks of pituitary gonadotropin suppression, group 3 testes showed a significant decrease (P less than .05) in MP/PD ratios from a control level of 2.6 +/- 0.3 and a decrease in the MP/beta-ATP ratio from 2.4 +/- 0.1 to 1.8 +/- 0.3. P-31 MR spectroscopy appears to be a potential method for noninvasively assessing testicular ischemic injury and the metabolic integrity of spermatogenesis.
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PMID:Assessment of testicular metabolic integrity with P-31 MR spectroscopy. 380 6

Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+] transient during each beat, a decrease in maximal Ca2+-activated force, or a shift in myofilament Ca2+ sensitivity. We measured developed pressure (DP) at several [Ca]0 (0.5-7.5 mM) in isovolumic Langendorff-perfused ferret hearts at 37 degrees C after 15 min of global ischemia (stunned group, n = 13) or in a nonischemic control group (n = 6). At all [Ca]0, DP was depressed in the stunned group (P less than 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P less than 0.05). Normalization of the DP-[Ca]0 relationship by corresponding MCAP (Ca0 sensitivity) revealed a shift to higher [Ca]0 in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Ca]0 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Ca]0 group were comparable to control (P greater than 0.05), and higher than in the stunned group (P less than 0.05). Myocardial [ATP] observed by phosphorus NMR failed to correlate with functional recovery. In conclusion, contractile dysfunction in stunned myocardium is due to a decline in maximal force, and a shift in Ca0 sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+] transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning.
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PMID:Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. 381 56

Phosphorus (31P) NMR spectra showing the relative concentrations of phosphocreatine, ATP, and Pi were recorded noninvasively from localized regions in the left ventricles of dog hearts in situ by using depth-resolved surface-coil spectroscopy at 1.5 T. Proton (1H) NMR surface-coil imaging was used to position 31P NMR coils and to determine the location of depth-resolved volumes immediately prior to 31P examination. Occlusion of the left anterior descending coronary artery produced regional ischemia detected as changes in the ratios of phosphocreatine, ATP, and Pi and by changes in the pH measured from the spectra. Spectral changes were not typically observed in regions adjacent to ischemic myocardium. Reperfusion produced some recovery, and ventricular fibrillation resulted in deterioration in high-energy metabolites. The location and size of ischemic tissue was measured by single-photon-emission computed tomography (SPECT) and gamma-ray counting or by staining excised hearts. The technique should permit the long-term noninvasive monitoring of the metabolic response of the heart to pathologic processes and allow assessment of interventions.
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PMID:Noninvasive detection and monitoring of regional myocardial ischemia in situ using depth-resolved 31P NMR spectroscopy. 386 49

To facilitate evaluation of the influence of myocardial phospholipid metabolites on the development of electrophysiologic abnormalities induced by ischemia, a method for the quantification of choline and ethanolamine phospholipids suitable for accurate and reproducible analysis of small amounts of myocardium was developed. The procedure combines chloroform and methanol extraction of phospholipids after tissue homogenization with subsequent separation by sequential thin-layer and high-performance liquid chromatography. Phosphorus in purified lipid classes was determined with the correction for recovery based on 14C-labeled internal standards.
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PMID:Quantification of choline and ethanolamine phospholipids in rabbit myocardium. 398 27


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