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

The acute cortical response to surgical brain isolation and subsequent extracorporal normoxic or 30 min hypoxic (PaO2 = 20 mm Hg) perfusions (hypoxic hypoxia with relative ischemia) was evaluated. Cerebral blood flow, arterial pH and CO2 were maintained constant during both perfusions; only the arterial oxygen content was changed. The isolated brain model used in this and previous investigations produces no qualitative ultrastructural changes in the neocortex following brain isolation and normoxic perfusion. However, the acute cortical structural response to 30 min of hypoxic hypoxia with relative ischemia demonstrated a number of important observations. Hypoxic hypoxia produced ultrastructural responses common to cerebral ischemia such as nuclear chromatin clumping, nucleolar condensation and cytoskeletal breakdown. Although neuronal abnormalities seen after 30 min of hypoxic hypoxia were similar to those acute neuronal changes observed following complete cerebral ischemia without recirculation, they differed three ways: (a) mitochondrial swelling and microvacuolation were observed in many cortical pyramidal neurons. (b) Glycogen particles within astroglial processes were observed even after a 30-min period of hypoxic hypoxia. (c) Perivascular astroglial swelling was minimal despite considerable perineuronal swelling. In contrast, incomplete cerebral ischemia produces mitochondrial changes similar to those in hypoxic hypoxia but also causes the depletion of tissue glycogen and perivascular glial swelling. Thus, hypoxic hypoxia with relative ischemia produces a unique acute ultrastructural response compared to either complete or incomplete cerebral ischemia.
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PMID:Acute ultrastructural response of hypoxic hypoxia with relative ischemia in the isolated brain. 281 6

We tested the hypothesis that depletion of glycogen prior to myocardial ischemia diminishes lactate buildup and improves functional recovery on reperfusion in the isolated rabbit heart. Cardiac glycogen was reduced either by substituting N2 for O2 in the perfusate or by perfusion with substrate-free solution, before the onset of ischemia. Hearts were subjected to either 30 minutes of normothermic (37 degrees C) or 60 minutes of hypothermic (4 degrees C) ischemia followed by 30 minutes of reperfusion with oxygenated Krebs-Henseleit buffer. Function was assessed by measuring peak left ventricular pressure at end-diastolic pressures ranging from 0 to 20 mm Hg. N2 perfusion for 15 minutes lowered myocardial glycogen by 60% and decreased ATP and phosphocreatine (p less than 0.001). Glycogen depletion did not decrease lactate accumulation during ischemia, but it impaired recovery with reperfusion (-46%, p less than 0.05). N2 perfusion for 5 minutes also reduced glycogen by 60%, but energy-rich phosphates were not reduced and functional recovery was still impaired (-40%, p less than 0.05). Perfusion with substrate-free medium diminished glycogen by 33% (p less than 0.05). Although lactate accumulation was significantly reduced (-45%, p less than 0.05), recovery following reperfusion was not improved. The results suggest that preservation of glycogen stores, but not the prevention of lactate buildup during ischemia, is beneficial for the recovery of function with reperfusion.
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PMID:Failure of glycogen depletion to improve left ventricular function of the rabbit heart after hypothermic ischemic arrest. 338 85

Rat kidneys were made ischemic for 5 to 120 seconds. Segments of individual nephrons were dissected from freeze dried sections and analyzed for ATP, phosphocreatine, glycogen, glucose, glucose-6-phosphate, lactate and creatine kinase. ATP fell most rapidly in proximal convoluted and straight tubules (PCT, PST) and distal convoluted tubules (DCT), and most slowly in glomerulus and papilla. Phosphocreatine levels ranged fivefold and was highest in DCT, where it approached that of brain. Creatine kinase ranged 100-fold with lowest level in PCT, where the ischemic fall in phosphocreatine was so slow as to suggest a function other than that of an energy reserve. Glycogen varied tenfold from modest levels in distal segments to very low levels in PST, and was not used rapidly in any segment. Glucose consumption and lactate production were most rapid in distal portions. High-energy phosphate consumption for the first 7.5 seconds of ischemia, calculated from these data, indicates roughly-equal energy metabolism in proximal and distal segments, with lower levels in papilla, and especially in glomerulus. The absolute values suggest that the in vivo metabolic rate of the nephron continued almost unabated for 5 or 10 seconds of ischemia.
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PMID:Change in energy reserves in different segments of the nephron during brief ischemia. 361 2

Canine Purkinje fibers were isolated by microdissection and analyzed for four enzymes of glycogen metabolism and eight related metabolites. Purkinje fiber glycogen levels were very high, confirming earlier reports. Glycogen synthesizing enzymes, glycogen synthase and UDP glucose pyrophosphorylase, were on the average 47 and 70% higher, respectively, in Purkinje fibers than in myocardium. Phosphorylase activity was approximately equal in the two tissue types, and phosphoglucomutase was 31% lower in Purkinje fibers. The metabolites of glycogen 6-phosphate were all higher in Purkinje fibers (P less than 0.001), but glucose 1,6-bisphosphate was lower by 50%. Phosphocreatine and ATP remained high in Purkinje fibers during 2 min of ischemia, while the phosphocreatine level in myocardium was falling by 75%. The results of this study suggest that the high glycogen synthetic capability, high precursor levels, and overall lower metabolic rate in Purkinje fibers compared with myocardium may explain the much higher glycogen levels.
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PMID:Enzymes and metabolites of glycogen metabolism in canine cardiac Purkinje fibers. 392 32

An important question in energy metabolism of the reperfused, previously ischemic myocardium is whether the return of a normal tissue adenosine triphosphate (ATP) content is a prerequisite for normal rates of oxygen consumption (that is, ATP turnover) and cardiac function. To study this problem, isolated working rat hearts were perfused with bicarbonate saline solution containing glucose (10 mM) at near physiologic work load. After 20 minutes, hearts were made totally ischemic by clamping the aortic and atrial lines for 5, 10 or 20 minutes and then were reperfused for another 10 minutes. Heart rate, aortic pressure, cardiac output and myocardial oxygen consumption were measured continuously. Adenine nucleotides, phosphocreatine, glycogen and the products of glycolysis were determined in freeze-clamped tissue extracts. Functional recovery was assessed by return of aortic pressure and oxygen consumption to preischemic values. Time required for return of function after reperfusion was 90 seconds after 5 minutes and 124 seconds after 10 minutes of ischemia. No recovery was observed after 20 minutes of ischemia. Tissue ATP content decreased significantly at the end of 5 (-38%) and 10 (-56%) minutes of ischemia and did not increase significantly at return of aortic pressure and oxygen consumption to preischemic values. Glycogen stores decreased by more than 50% at the end of 10 minutes of ischemia and did not normalize on recovery. In contrast to ATP or glycogen, the phosphocreatine content decreased to even lower levels at the end of ischemia, but returned to levels higher than the control level after recovery from 5 to 10 minutes of ischemia in association with return of function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy metabolism in reperfused heart muscle: metabolic correlates to return of function. 403 1

Glucose, insulin, potassium (GIK: 300 g glucose + 50 U insulin + 80 mEq KC1/L) was administered to anesthetized dogs as a 30-ml bolus followed by 1.5 ml/kg/h for 2 h. Five populations were studied: control (C, n = 6); 60 min hypothermic arrest both without (I, n = 6) and with pretreatment (I + GIK, n = 6); 60 min hypothermic arrest followed by reperfusion without (R, n = 6) and with pretreatment (R + GIK, n = 6). Glycogen content declined during the ischemic and reperfusion periods whether or not GIK pretreatment was utilized. Glycogen values did not differ significantly among the four groups. GIK pretreatment significantly protected sarcoplasmic reticulum (SR) calcium uptake rates. SR Ca2+ + Mg2+ adenosine triphosphatase (ATPase) activity was unaffected in the I group, depressed in the R group, but protected by GIK pretreatment. Myofibrillar pCa-ATPase activity was significantly depressed in the I group and unaffected by GIK pretreatment. In the R + GIK group, myofibrillar pCa-ATPase activity was identical to controls at all calcium concentrations except for Vmax. In vitro, generation of the superoxide anion by a xanthine-xanthine oxidase system at pH 7.0 significantly depressed both SR calcium uptake and ATPase activity, and this depression was partially reversible by glucose. Generation of the hydroxyl free radical and pH 6.4 significantly depressed calcium uptake but not ATPase activity, and this depression was reversible with glucose + superoxide dismutase. GIK pretreatment exerts a protective effect on the excitation-contraction coupling system during hypothermic global ischemia and reperfusion. Glycogen augmentation after short-term GIK infusion was not significantly different. It is hypothesized that an additional mechanism by which GIK may protect subcellular function is by serving as a scavenger of free radicals generated during the ischemic/reperfusion process.
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PMID:Glucose, insulin, potassium protection during the course of hypothermic global ischemia and reperfusion: a new proposed mechanism by the scavenging of free radicals. 618 57

The excitation-contraction coupling system of the global ischemic hypothermic myocardium was studied by evaluating the functional integrity of the isolated sarcoplasmic reticulum (SR) and myofibrils and determining glycogen decay 30 and 60 min after the onset of surgically induced global ischemia. Calcium uptake by the SR from both the 30- and 60-min groups was depressed (control 0.940 +/- 0.05, 30 min 0.430 +/- 0.033, 60 min 0.535 +/- 0.033 mumol Ca2+ . mg-1 . min-1; P less than 0.001). In contrast SR Ca2+-ATPase activity was not different in the three groups (control 1.150 +/- 0.080, 30 min 1.468 +/- 0.025, 60 min 1.338 +/- 0.199 mumol Pi . mg-1 . min-1; P greater than 0.2). Glycogen decay in the hypothermic group was depressed compared to control (control 7.52 +/- 2.01, 30 min 6.152 +/- 1.16, 60 min 5.814 +/- 1.76 mumol glycogen/mg myocardium; P less than 0.05). Myofibrillar pCa-ATPase curves in both hypothermic ischemic groups were depressed (maximal ATPase activity; control 0.160 +/- 0.028, 30 min 0.1130 +/- 0.01, 60 min 0.127 +/- 0.008 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km for the hypothermic ischemic groups. It is concluded that the excitation-contraction coupling system of the hypothermic ischemic myocardium at 1 h is characterized by a defect in the calcium transport system of the sarcoplasmic reticulum with preservation of the Ca2+-ATPase, a depression of the myofibrillar ATPase activity, a decrease in affinity, and the preservation of adequate glycogen stores. It is hypothesized that these defects may explain an observed depression in myocardial function following reperfusion.
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PMID:Excitation-contraction coupling in hypothermic ischemic myocardium. 645 66

Glycogen synthesis from D-[1-13C]glucose was observed in the perfused rat heart by 13C-NMR spectroscopy at 62.9 MHz. The glycogenogenesis was stimulated by pretreatment of the animals with isoprenaline. Whereas in hearts from control rats the incorporation of D-[1-13C]glucose into the glycogen remained below the detection threshold, 5 min proton-decoupled 13C-NMR spectra revealed, in hearts from treated rats, a significant labelling of the glycogen within the first minutes of the perfusion and a further linear increase of the glycogen resonance for up to 25 min. This model was used to monitor the appearance of 13C-labelled lactate during ischemia.
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PMID:Glycogen metabolism: a 13C-NMR study on the isolated perfused rat heart. 650 61

The cardioprotective effects of lidoflazine, a calcium entry blocker, were tested in patients undergoing multiple aorta-coronary bypass grafting (at least four grafts). Intermittent aortic cross-clamping at 25 degrees to 28 degrees C was used. Mean cross-clamp time was 11 minutes for one distal anastomosis. Patients were randomized into three groups: a control group (I), a group (II) pretreated with 0.5 mg . kg-1 lidoflazine intravenously before cardiopulmonary bypass (CPB), and a group (III) pretreated with 1 mg . kg-1 lidoflazine intravenously. The following markers of ischemia are used: (1) adenosine triphosphate (ATP), creatine phosphate (CP) and glycogen determined in transmural left ventricular biopsy specimens taken at the beginning and end of CPB; (2) ultrastructure in a similar pair of specimens; and (3) hemodynamic recovery 15 minutes after cessation of CPB. At the end of the intervention, ATP decreased to 73% in Group I but remained unchanged in Groups II (98%) and III (88%). CP decreased to 82% in Group I and remained unaltered in Groups II (100%) and III (110%). Glycogen decreased in Group I (to 44%) and in Group II (78%) but remained unchanged in Group II (138%). Ultrastructural study showed better preservation of the glycocalyx and sarcolemma in Group III than in Group I. Left ventricular stroke work index remained unaltered after CPB in Group III but decreased in Groups I and II to about 60% of its initial value. Thus lidoflazine pretreatment protects the myocardium in a dose-dependent manner against deterioration of myocardial function and structure.
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PMID:Cardioprotective effects of lidoflazine in extensive aorta-coronary bypass grafting. 660 46

The hemodynamic changes which occur when clamping and unclamping the aorta during reconstructive surgery might be a threat to the elderly patient with concomitant cardiac disease. In addition, the cross-clamping induces a temporary ischemia of the legs, with severe metabolic derangement after the release of the aortic clamp. We have studied the effect of a intraoperative adrenergic block (phenoxybenzamine plus metoprolol) on the central circulation and the skeletal metabolism in 14 patients undergoing aortic reconstruction to treat occlusive arteriosclerotic disease. Cardiac output, heart rate, arterial and pulmonary artery pressures, and cardiac filling pressures, as well as femoral venous blood flow were studied. Biopsy specimens of the lateral vastus muscle and blood samples from the radial artery and iliac vein were taken before aortic clamping, and before, 30 minutes, four and 16 hours after the aorta was unclamped, as well as five days postoperatively. In addition, intramuscular temperature and pH were measured. Glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and lactate and pyruvate concentrations in iliac venous and radial arterial blood were determined using enzymatic fluorometric techniques. Mean arterial blood pressure (MAP) averaged 80 mmHg before clamping, chiefly because of the low systemic vascular resistance (SVR), and left ventricular stroke work (LVSW) was normal. At clamping MAP, SVR, LVSW, remained unchanged. MAP and LVSW were unaffected even though SVR decreased slightly after the aorta was unclamped and resulted in an increased cardiac output, mainly due to a higher stroke volume. No major change in the pulmonary circulation was observed. During clamping the muscle lactate/pyruvate ratio increased, intramuscular pH and femoral venous blood flow decreased indicating insufficient tissue perfusion. Energy charge (EC), the adenylate (ATP + ADP + AMP) and creatine (PCr + Cr) pools were, however, unchanged. In spite of a restored blood flow to the legs, a severe metabolic derangement of the muscle was observed after declamping, with lowered EC, ATP + ADP + AMP and PCr + Cr indicating cellular damage. No improvement in the condition of the cells was observed 16 hours after operation. In conclusion, we found that by using neurolept anesthesia and an intraoperative adrenergic block in combination with a differentiated fluid therapy the central circulation stabilized and was largely unaffected by the clamping and unclamping procedures. In spite of the improved central hemodynamics no favorable effect on the skeletal muscle metabolism was observed.
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PMID:Temporary incomplete ischemia of the legs induced by aortic clamping in man: effects on central hemodynamics and skeletal muscle metabolism by adrenergic block. 745 55


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