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)

Some metabolites (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate, citrate, alpha-ketoglutarate, succinate, fumarate, malate, glutamate, aspartate, gamma-aminobutyrate, glutamine, alanine, NH+4) were measured in rat cerebral cortex after 5 minutes of complete compression ischemia, as well as after 5, 15, or 30 minutes of recirculation following 5 minutes of ischemia. Complete ischemia induced a drop of glycolytic substrates and intermediates, consistent with the increase of lactate, succinate, alanine, and gamma-aminobutyrate, and with the decrease of malate, fumarate, and alpha-ketoglutarate. These events may be regarded as an expression of the activation of the gamma-aminobutyrate cycle and of the succinate cycle, where succinate itself, in the absence of O2, acts as a terminal electron acceptor. During post-ischemic recovery, cerebral parameters tended to normalize, except for the further increase of alanine and the still higher than normal content of both succinate and gamma-aminobutyrate, as an expression of the possible activation of the gamma-glutamyl and gamma-aminobutyrate cycles during recovery.
 ...
PMID:Relationships between gamma-aminobutyrate and succinate cycles during and after cerebral ischemia. 709 4

The simultaneous utilization of carbohydrates and amino acids in the metabolic response to oxygen deprivation was studied i the isolated rat heart initially perfused according to Langendorff and submitted to periods of 2, 5, 10 and 15 min of complete ischemia. The results of the measurement of metabolite contents showed : (1) an immediate decrease of glycogen, pyruvate, alpha-ketoglutarate and aspartate; (2) a delayed decrease of citrate and glutamate; (3) an immediate and continuous increase of lactate and succinate; (4) a delayed increase of alanine; (5) a transient increase of malate + fumarate. The end products of anaerobic metabolism are lactate, which is an index of glycolytic activity, and alanine and succinate, which are indexes of amino acid fermentation. Succinate originates from aspartate, and alanine originates from glutamate. The amino acid pathway does not seem of importance in the production of ATP compared to glycolysis. However, its eventual role and the physiological implication of these reactions in the resistance of strict aerobic organisms to oxygen deprivation are discussed.
 ...
PMID:[Simultaneous use of carbohydrates and amino acids during total ischemia in the isolated rat heart (author's transl)]. 724 99

It has been established that malonate-like action of isoquinoline derivatives (papaverine and nospan) on respiratory function of myocardial mitochondria leads to inhibition of the accumulation rate of Ca2+ by these organelles on the use of glutamate and alpha-ketoglutarate as substrates. A greater inhibition of Ca2+ transport rate in the mitochondria is observed in the presence of glutamate. It has been validated theoretically that the decreased intensity of Ca2+ accumulation is aimed at protecting the mitochondria from irreversible lesions in ischemia. Nitroglycerin and sodium nitrite do not affect Ca2+ exchange in the mitochondria.
 ...
PMID:[Protection of myocardial mitochondria from penetration by calcium ions using isoquinoline and phenothiazine derivatives]. 726 1

High-energy phosphate content and mitochondrial function were analyzed at the initiation and completion of ischemic contracture in dog hearts exposed to normothermic ischemia while on cardiopulmonary bypass. Contracture initiation and completion were detected by a balloon catheter placed within the left ventricle. In seven dogs, inner and outer layers of the myocardium were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). ATP and CP content in these two layers were compared prior to ischemia and at contracture initiation and completion. Inner layer ATP levels were 23.88 +/- 0.73 (mean +/- SM) mu moles/gm dry weight prior to ischemia, 5.14 +/- 0.49 at initiation, and 0.73 +/- 0.2 at completion. Inner layer CP content was 41.29 +/- 0.87 prior to ischemia, 3.49 +/- 0.34 at initiation, and 4.06 +/- 0.48 at completion. Mitochondrial respiratory control indices (RCI) were assayed in a second group of seven dogs prior to ischemia, at contracture initiation, and at contracture completion and were, respectively, 11.5 +/- 1.18, 3.1 +/- 0.43 and 1.76 +/- 0.29 (alpha ketoglutarate as substrate). Despite the specific degrees of metabolic deterioration associated with the events of contracture, ischemic time required to develop contracture initiation and completion was variable, ranging from 29.5 to 72 minutes for initiation and 60.25 to 101 minutes for completion. A third group of five dogs had biopsy specimens taken for ATP at fixed ischemic time intervals, and at 45 minutes of ischemia they were found to have greater ranges in ATP values than the ranges associated with contracture initiation. In contrast to ischemic time, the physiological events of ischemic contracture are reliable predictors of the degree of metabolic injury in the intact dog heart exposed to normothermic ischemic arrest during cardiopulmonary bypass.
 ...
PMID:Metabolic deterioration during global ischemia as a function of time in the intact normal dog heart. 745 37

The effect of hydroxyethyl starch on pancreas preservation with cardioplegic histidine-tryptophan-ketoglutarate solution (HTK) was investigated. The study was performed using an in vitro reperfusion system of the porcine pancreas. During organ preservation pancreatic weight, arterial pressure, volume flow, and washout of amylase and lactate were quantified. Addition of hydroxyethyl starch did not affect arteriovenous volume flow or washout of amylase and lactate during protective perfusion after pancreas preparation. However, hydroxyethyl starch in HTK prevented an increase in pancreatic weight at the end of the protective perfusion (102.2 +/- 4.55% vs 127.8 +/- 4.62% in controls; p < 0.005) and after 24 h cold ischemia (72.9 +/- 3.91% vs. 83.5 +/- 3.49% in controls; p < 0.05). Hydroxyethyl starch did not affect postischemic organ quality assessed during reperfusion in a perfusion chamber by pancreatic vascular resistance, amylase and lactate release, insulin secretion, and oxygen consumption. We conclude that hydroxyethyl starch does not bring about any further improvement in immediate postischemic organ quality assessed in an in vitro reperfusion system.
 ...
PMID:Hydroxyethyl starch does not improve pancreas preservation with HTK. 768 42

The current shortage of transplantable organs has renewed interest in kidneys obtained from non-heart-beating donors. Kidneys from these donors have suffered warm ischemia (WI). The effectiveness of two preservation solutions, i.e., the University of Wisconsin (UW) and the histidine tryptophan ketoglutarate (HTK) solutions, for preservation of kidneys that have been subjected to WI was tested in dogs. The left kidney was autotransplanted after 30 min of WI, and subsequent 24-hr cold storage (CS) in either UW (n = 6) or HTK (n = 6), with immediate contralateral nephrectomy. Surgical biopsies from the cortex were taken before WI, after 30 min of WI, after 24 hr of CS, and after 1 hr of reperfusion for electron microscopy and for analysis of energy metabolites. At 2 weeks after transplantation in the UW group, 4 out of 6 and, in the HTK group, 1 out of 6 dogs survived. As from day 2, serum creatinine was lower in the UW group as compared with the HTK group (P < 0.05). After 24 hr of CS, in the HTK group the luminal membranes of proximal tubular cells were partly denuded of microvilli. Moreover, the tubular lumen was filled with blebs and debris. In the UW group, the brush borders remained intact, although microvilli were swollen. Energy metabolites were analyzed with HPLC. Thirty minutes of WI resulted in a +/- 45% reduction of total adenine nucleotide (TAN) content. During CS, TAN levels further decreased in both groups; however, after 24 hr of CS, the levels of adenosine, inosine, hypoxanthine, and xanthine were significantly higher in the UW group as compared with the HTK group (P < 0.05, P < 0.01, P < 0.01, P < 0.01). At 1 hr of reperfusion, TAN levels were higher in the UW group as compared with the HTK group (4.66 +/- 0.16 vs. 4.02 +/- 0.28, P < 0.05). Our results show that UW is a superior solution compared with HTK in the preservation of ischemically damaged kidneys, demonstrating better survival, better recovery of kidney function, better protection against ischemia-induced ultrastructural damage, and better preservation of energy metabolism indicated by (a faster) regeneration of TAN levels after reperfusion.
 ...
PMID:University of Wisconsin solution is superior to histidine tryptophan ketoglutarate for preservation of ischemically damaged kidneys. 797 36

The brain mitochondrial NAD+/NADH ratio, as a reflection of the oxidation-reduction (redox) state of cellular compartment, was determined under conditions of hypoxia, anoxia, hypoxia-ischemia, complete ischemia and hypoglycemia in immature rats. NAD+/NADH ratios were calculated from changes in the concentrations of specific oxidative substrates and calculated intracellular pH during cerebral metabolic stress. The results suggest that the use of the acetoacetate/beta-hydroxybutyrate substrate couple provides a more accurate prediction of the mitochondrial redox state under adverse conditions than use of the alpha-ketoglutarate/glutamate couple. It is possible that the mitochondrial oxidation seen with the latter substrate couple during cerebral metabolic stress might reflect a population of cells (neurons or glia) which are substrate-deprived relative to the rest of the brain in the setting of metabolic stress produced by oxygen deficiency.
 ...
PMID:Cerebral mitochondrial redox states during metabolic stress in the immature rat. 798 46

Over a 30-month period, 60 patients (30 in each group) suffering from end-stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution. Entry criteria for both groups were: age (18-65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data pre- and post-transplantation, as well as follow-up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15 h (n = 7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15 h.
 ...
PMID:Comparison of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution for organ preservation in human liver transplantation. A prospective, randomized study. 806 Apr 66

A new 13C NMR technique for measuring substrate utilization by the citric acid cycle based on an analysis of succinate 13C isotopomers is presented. The relative contribution of up to three different labeling patterns in acetyl-CoA entering the citric acid cycle may be determined under non-steady-state conditions. We present experimental data from perfused rat hearts subjected to a brief period of ischemia, where both succinate and glutamate resonances were observed in the 13C spectrum. The contributions of labeled exogenous acetate and lactate and unlabeled sources to the acetyl-CoA pool were compared using this succinate analysis and a previously published glutamate analysis [Malloy et al. (1990) Biochemistry 29, 6756-6761], and the two methods give identical results. This indicates that the succinate and glutamate isotopomers originated from a common alpha-ketoglutarate pool, verifying that glutamate is in isotopomeric equilibrium with alpha-ketoglutarate under these conditions.
 ...
PMID:Sources of acetyl-CoA entering the tricarboxylic acid cycle as determined by analysis of succinate 13C isotopomers. 821 1

Application of the University of Wisconsin cold storage solution has rapidly expanded to include medium-term to long-term preservation of virtually all intraabdominal organs. Its use in intrathoracic organ transplantation has also been suggested. We therefore examined the efficacy of the University of Wisconsin solution in a primate allotransplantation model for preservation of hearts, and as a simple single-solution system for static preservation of heart-lung blocks, for periods of ischemia ranging from 6 to 24 hours. For comparison, we employed the histidine-tryptophane-ketoglutarate cardioplegic solution of Bretschneider. University of Wisconsin solution provided superior results with regard to clinical outcome and hemodynamic recovery of hearts after ischemic periods of up to 16 hours. This was in contrast to Bretschneider's solution, which allowed storage of hearts for periods of only up to 10 hours. Heart-lung blocks were equally well preserved with either University of Wisconsin or Bretschneider's solution after 6 to 12 hours, although the University of Wisconsin solution group exhibited a more notable increase in pulmonary water content. This was in accordance with histological data, which suggested that, although hemodynamic recovery of hearts stored for periods longer than 10 hours was poor, preservation of pulmonary ultrastructure was far superior using Bretschneider's solution as compared with University of Wisconsin solution after an ischemic period of up to 16 hours.
 ...
PMID:Extended cardiopulmonary preservation: University of Wisconsin solution versus Bretschneider's cardioplegic solution. 849 20


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