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

The brain damage that evolves from perinatal cerebral hypoxia-ischemia may involve lingering disturbances in metabolic activity that proceed into the recovery period. To clarify this issue, we determined the carbohydrate and energy status of cerebral tissue using enzymatic, fluorometric techniques in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-day postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37 degrees C. This insult is known to produce tissue injury (selective neuronal necrosis or infarction) predominantly in the cerebral hemisphere ipsilateral to the carotid artery occlusion in 92% of the animals. Rat pups were quick-frozen in liquid nitrogen at 0, 1, 4, 12, 24, or 72 h of recovery; littermate controls underwent neither ligation nor hypoxia. Glucose in both cerebral hemispheres was nearly completely exhausted during hypoxia-ischemia, with concurrent increases in lactate to 10 mmol/kg. During recovery, glucose promptly increased above control values, suggesting an inhibition of glycolytic flux, as documented in the ipsilateral cerebral hemisphere by measurement of glucose utilization (CMRglc) at 24 h. Tissue lactate declined rapidly during recovery but remained slightly elevated in the ipsilateral hemisphere for 12 h. Phosphocreatine (P approximately Cr) and ATP in the ipsilateral cerebral hemisphere were 14 and 26% of control (p less than 0.001) at the end of hypoxia-ischemia; total adenine nucleotides (ATP + ADP + AMP) also were partially depleted (-46%).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Carbohydrate and energy metabolism during the evolution of hypoxic-ischemic brain damage in the immature rat. 230 39

The catabolism of adenine nucleotides (AdN) in rat soleus muscle (predominantly slow twitch) is very different from that in fast-twitch muscle. AMP deaminase is highly inhibited during brief (3 min) intense (120 tetani/min) in situ stimulation, resulting in little inosine 5'-monophosphate (IMP) accumulation (0.21 mumol/g). Even with ligation of the femoral artery during the same brief intense contraction conditions there is surprisingly little increase in IMP (0.37 mumol/g), although AdN depletion is evident (-1.30 mumol/g). We have tested the hypothesis that accumulation of purine nucleosides and bases accounts for the AdN depletion by measuring purine degradation products using high-performance liquid chromatography. There was no stoichiometric accumulation of purine degradation products to account for the observed AdN depletion even though metabolite recovery was essentially quantitative. We hypothesis that under these conditions AdN are converted to a form different from purine nucleoside and base degradation products. In contrast to the inhibition of AMP deamination seen during brief ischemia, slow-twitch muscle depletes a substantial fraction (28%) of muscle AdN (1.75 mumol/g) that can be accounted for stoichiometrically as purine degradation products during an extended 10-min ischemic period of mild (12 tetani/min) contraction conditions. IMP accumulation (1 mumol/g) is most prominent with inosine, accounting for 23% (0.4 mumol/g) of the depleted AdN, showing that slow-twitch red muscle is capable of both AMP deamination and the subsequent production of purine nucleosides during an extended period of ischemic contractions. The present results indicate that AdN metabolism in the soleus muscle is complex, yielding expected degradation products or a loss of total purines, depending on contraction conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adenine nucleotide degradation in slow-twitch red muscle. 230 68

An in vivo rat hindlimb tourniquet ischemia model was used to study the purine nucleotide metabolism in response to 2, 4, and 6 h of ischemia and to the same ischemia periods followed by 1 h of reperfusion. All purine intermediates from ATP to uric acid were determined in skeletal muscle with a high-performance liquid chromatography (HPLC) system. The major metabolic event during ischemia is to temporarily save the nucleotide pool as inosine-5'-monophosphate (IMP. On restitution of the circulation as the energy state recovers, the IMP is converted back to AMP via the purine nucleotide cycle. Six hours of ischemia is associated with irreversible damage and no recovery fo the adenine nucleotides on reperfusion. Fast-twitch muscles appear to be more susceptible than slow-twitch muscles in response to ischemia and reperfusion. A severalfold increase of intracellular hypoxanthine occurred during ischemia, whereas uric acid formation is observed only after reperfusion. These findings are discussed in relation to the proposed role of xanthine oxidase, as an enzyme generating tissue-injurious oxygen free radicals.
 ...
PMID:Purine metabolism after in vivo ischemia and reperfusion in rat skeletal muscle. 236 Jun 63

The effect of allopurinol was studied in a normothermic liver ischemia rat model. Functional (bile flow) and biochemical parameters (high-energy phosphates, ATP, ADP, AMP), energy charge, hypoxanthine and xanthine were determined prior to and during 60 min of ischemia followed by 120 min of reperfusion. Allopurinol given in the preischemic period (50%) and as a bolus (50%) prior to reperfusion improved liver function significantly, whereas allopurinol given in the preischemic period (50%) and after start of reperfusion (50%) had no effect. The data indicates that allopurinol given prior to reperfusion saved hypoxanthine which was used for ATP resynthesis during reperfusion.
 ...
PMID:60 min normothermic liver ischemia in rats: allopurinol improves energy status and bile flow during reperfusion. 237 23

The endogenous level of epidermal cyclic AMP does not remain constant but increases rapidly and transiently after removal of the tissue; this is known as the "ischemia" effect. UVB-irradiated epidermis which shows increased beta-adrenergic response revealed an increased ischemia effect, while psoriatic involved epidermis which shows decreased beta-adrenergic response revealed a decreased ischemia effect. Because of the similar rise-and-fall pattern between the ischemia effect and the beta-adrenergic response, the mechanism of the ischemia effect was investigated, especially in terms of the beta-adrenergic relationship. The ischemic rise of epidermal cyclic AMP was well preserved after 6 h pretreatment at 4 degrees C, and, following the pretreatment, the skin markedly increased its cyclic AMP level by the 37 degrees C treatment with 1 mM isobutylmethyl xanthine. The addition of propranolol or cimetidine at the time of 37 degrees C treatment (following the 4 degrees C pretreatment) had no effect on the ischemia effect; both skin groups markedly increased their cyclic AMP levels to an extent similar to that of the control skin. However, the addition of propranolol at the time of both preincubation (at 4 degrees C) and incubation (at 37 degrees C) markedly decreased the ischemic rise of cyclic AMP. Similar treatment by cimetidine had no effect on the ischemia effect. There was no significant difference in cyclic AMP phosphodiesterase activities among skin groups by propranolol or cimetidine pretreatment. These results indicate that the so-called ischemic rise of epidermal cyclic AMP is actually the beta-adrenergic adenylate cyclase-dependent process. Our results also indicate that the magnitude of the "ischemic" rise of cyclic AMP is generally parallel to the beta-adrenergic responsiveness of epidermis.
 ...
PMID:"Ischemic" rise of epidermal cyclic AMP is a beta-adrenergic adenylate cyclase-dependent process. 242 5

The protective effect of calcium antagonists on ischemic heart has been attributed to decreased energy expenditure. We administered one of the newer calcium antagonists, DL-bepridil (0.1-10 microM), to Langendorff rat hearts 10 or 15 min before ischemia (flow reduction approximately 80%). Vasodilation during normoxia was already observed with 0.3 microM DL-bepridil (flow increase 34%, p less than 0.005). This concentration decreased normoxic contractility and ischemic purine release, a marker for ATP breakdown. In the absence of bepridil, purine release of hearts that were made ischemic was 8.5-fold higher than that of normoxic control hearts. With 1 microM bepridil, the ischemic purine efflux was suppressed by 55% (p less than 0.05), with negative inotropy (p greater than 0.05) during normoxia. At 3 and 10 microM, bepridil decreased normoxic contractility by 40 and 75%, respectively (p less than 0.001), concomitant with a decrease in ischemic purine release by 80 and 76%, respectively (p less than 0.01). At the end of ischemia, myocardial ATP and creatine phosphate had decreased by 22 and 55%, respectively (p less than 0.05), and ADP, AMP, and creatine had increased 1.5-3.5-fold (p less than 0.05). Bepridil (3 microM) normalized the adenine nucleotide values; creatine and creatine phosphate approached control levels. The dose-dependent protection of the ischemic heart by bepridil appears to arise from its negative inotropic action during normoxia.
 ...
PMID:Protection by bepridil against myocardial ATP-catabolism is probably due to negative inotropy. 244 Nov 54

Delayed afterdepolarizations (DADs) are Ca++-dependent electrophysiological abnormalities, which are evoked by a variety of conditions that induce intracellular Ca++ overload, including fast pacing, isoproterenol, dibutyryl cyclic AMP, and intracellular injection of Ca++. Since Ca++ overload is suspected of playing a role in both ischemic and reperfusion cellular damage, a reasonable hypothesis would be that DADs could play a role in ischemic or reperfusion arrhythmias. No direct proof has, however, been obtained for such a role for DADs. We propose that DADs could be associated with arrhythmias in which there is Ca++ overload of sufficient magnitude to cause an increased oscillatory release of Ca++ from the sarcoplasmic reticulum (SR), provided energy is available in the form of ATP. A sustained increase of Ca++ is likely to reflect energy depletion and therefore exclude a significant contribution of DADs to arrhythmia development. Thus, DADs are more likely to play a role in: (i) reperfusion arrhythmias and (ii) arrhythmias arising in moderately ischemic tissue, than in severe ischemia with marked energy depletion.
 ...
PMID:Proposed role of energy supply in the genesis of delayed afterdepolarizations--implications for ischemic or reperfusion arrhythmias. 244 88

The voltage- and time-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. These slow channels appear to behave kinetically, on a population basis, as if their gates open, close, and recover more slowly than those of the fast Na+ channels. In addition, the slow channel gates operate over a less negative (more depolarized) voltage range. Tetrodotoxin does not block the slow channels, whereas the calcium antagonistic drugs, Mn2+, Co2+, and La3+ ions do. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). During transient regional ischemia, the selective blockade of the slow channels, which results in depression of the contraction and work of the afflicted cells, might protect the cells against irreversible damage by helping to conserve their ATP content. Reperfusion arrhythmias may be caused by the breakdown of this protective mechanism, in that, upon reperfusion, the Ca2+ slow channels may recover before the cells are capable of handling the greater Ca2+ influx (Fig. 20). As depicted in this figure, the Ca2+ slow channels may recover their function before the ATP level is sufficiently recovered to allow bail-out of the intracellular Ca2+. In addition, the generation of free radicals upon reperfusion may injure the Ca-ATPase and other enzymes involved in Ca2+ metabolism. The net effect of this would be to cause Ca2+ overload of the cells and SR, with subsequent delayed after-depolarizations (DADs) leading to triggered automaticity and arrhythmias. Following blockade of the fast Na+ channels in myocardial cells with TTX or by voltage-inactivating them in 25 mM (K)0, catecholamines, angiotensin-II, histamine, and methylxanthines rapidly allow the production of slowly-rising Ca2+-dependent action potentials by increasing the number of Ca2+ slow channels available for voltage activation and/or their mean open time. Concomitantly, these compounds rapidly elevate intracellular cyclic AMP levels, suggesting that cyclic AMP is somehow related to the functioning of the slow channels. Exogenous cyclic AMP produces the same effect, but much more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation of calcium slow channels of cardiac muscle by cyclic nucleotides and phosphorylation. 245 7

Fluorescein-isothiocyanate dextran (FITC-dextran), a dye confined to the vascular space, was infused via the hepatic artery and portal vein into perfused livers from fed rats treated with diethylnitrosamine for 4 to 5 months. Fluorescence due to FITC-dextran was detected with fiberoptic microlight guides placed on surface nodules of about 5 mm in diameter. Nodules were categorized into groups with normal and compromised microcirculation based on their fluorescence following infusion of FITC-dextran. Similar results were obtained when nodules were classified based on reflectance of trypan blue. Despite compromised microcirculation, ATP and ADP levels as well as ATP/ADP ratios were comparable in both groups of nodules; however, AMP was elevated in FITC-dextran-negative nodules (i.e., those with compromised microcirculation). Nodules with compromised microcirculation also contained higher glucose and lactate levels than nodules that were well perfused; however, glycogen was five times lower than in FITC-dextran-positive nodules. Fasting reduced ATP/ADP ratios in poorly perfused nodules in comparison to well-perfused nodules. In perfused livers from fed rats where glycogen was high, however, ATP/ADP ratios and rates of ATP depletion during ischemia were the same in well-perfused and poorly perfused nodules. Products of glycogen breakdown (e.g., glucose and lactate) were elevated in nodules from livers of fed but not fasted rats. The results indicate that alteration of perfusion of hepatic nodules does not change ATP levels nor the capacity of nodules to utilize high energy phosphate during anoxia. Thus, near normal energy status is maintained from glycogen metabolism in poorly perfused nodules via glycolysis. Since basal ATP content and utilization is comparable in well and poorly perfused nodules, compromised energy status is unlikely to explain selection of nodules that regress to near normal hepatocytes.
 ...
PMID:Adenine nucleotides and carbohydrates in subpopulations of hepatic nodules with normal and compromised microcirculation. 247 May 3

High energy phosphate levels are depressed following global ischemia and require several days to completely recover. Short-term methods to enhance ATP recovery have included infusion of ATP precursors, inhibition of enzymes that catabolize AMP, and membrane transport stabilization. Several precursors have been used to augment adenine nucleotide synthesis including adenosine, inosine, adenine, and ribose. Because of the short-term nature of previous experiments, recovery had been incomplete and the effects in the intact animal unknown. The purpose of this study was to determine the effects of ribose infusion in a long-term model of global ischemia and attempt to identify the precursor which limits myocardial ATP regeneration in the intact animal. Global myocardial ischemia (20 min, 37 degrees C) was produced in dogs on cardiopulmonary bypass. With reperfusion either ribose (80 mM) in normal saline or normal saline alone was infused at 1 ml/min into the right atrium and the animals were followed for 24 hr. Ventricular biopsies were obtained through an indwelling ventricular cannula prior to ischemia, at the end of ischemia, and 4 and 24 hr postischemia and analyzed for adenine nucleotides and creatine phosphate levels. Radiolabeled microspheres were used to measure myocardial and renal blood flows and no significant difference was found between ribose-treated control groups. In both groups, myocardial ATP levels fell by at least 50% at the end of ischemia. No significant ATP recovery occurred after 24 hr in the control dogs, but in the ribose-treated animals, ATP levels rebounded to 85% of control by 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enhanced high energy phosphate recovery with ribose infusion after global myocardial ischemia in a canine model. 249 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>