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)

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
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PMID:Insulin: fundamental mechanism of action and the heart. 18 67

In Langendorff-perfused rat hearts, the perfusion pressure was reduced from 100 cm H2O to 20 cm H2O for 30 minutes to produce a model of global ischemia with a residual oxygen uptake. The release of lactate dehydrogenase (LDH) and the occurrence of ventricular arrhythmias during reperfusion were dependent on the substrate. Glucose-perfused hearts had the highest rates of glycolytic ATP production (2.5 mumol/g per min) during ischemia with normal contents of tissue cyclic adenosine 3',5'-monophosphate (cAMP) and, during reperfusion, the release of LDH was lowest and severe ventricular arrhythmias did not occur. In pyruvate-perfused hearts, glycolysis was inhibited during ischemia, the rate of production of glycolytic ATP was only 0.5 mumol/g per min. and tissue cAMP doubled; during reperfusion, LDH release was 14-fold higher and ventricular arrhythmias were more severe. Total tissue contents of ATP and phosphocreatine were similar in glucose- and in pyruvate-perfused hearts. In hearts perfused with acetate, there was virtually no glycolytic ATP synthesized during the last 5 minutes of ischemia and cAMP increased further. Acetate- and palmitate-perfused hearts showed greatest release of LDH and had severest arrhythmias during reperfusion, suggesting that it was the metabolic and not the detergent effects of palmitate that were operating. Lipolysis was not a major factor in the cause of reperfusion LDH release. A role of glycolytic ATP in the maintenance of membrane integrity is postulated.
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PMID:Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion. 20 59

Analysis of the ischemic dog heart preparation described in the preceding paper indicates that it is an analogue in slow motion of the tissue in the center of a cardiac infarct. It is respiring very slowly and not capable of performing mechanical work. Glycolysis starts up with both glucose and glycogen as inputs. Later hexokinase and to some extent phosphofructokinase become limiting owing to inhibitor accumulation or acidosis. Metabolism then results primarily from cAMP-driven glycogenolysis, largely limited by the glycogen debranching enzymes at later times, with accumultion not only of lactate and alpha-glycerophosphate but of glucose as well. Amino acid levels oscillate with time while fatty acids accumulate at late times. The elevation of cAMP at later times may involve disturbances in its metabolism as well as mechanisms such as adenosine accumulation that are more important in cardiac ischemia than in normal heart. The clinical implications of this behavior are discussed.
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PMID:Metabolism of totally ischemic excised dog heart. II. Interpretation of a computer model. 22 80

The effects of ligation of both common carotid arteries in the gerbil on the levels of PGF2 alpha, TXB2, HETE and of energy metabolites in brain cortex, have been investigated. Also, in the same experimental conditions the changes of cyclic AMP in brain cortex, cerebellum, striatum and hippocampus have been monitored. ATP, glycogen, glucose and phosphocreatine decrease whereas, lactate and cyclic AMP are enhanced in the ischemic brain, as previously reported. In contrast, levels of arachidonic acid metabolites are not modified. During ischemia following decapitation, instead, PGF2 alpha, and TXB2, show considerable increase.
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PMID:PGF2 alpha, thromboxane B2 and HETE levels in gerbil brain cortex after ligation of common carotid arteries and decapitation. 23 May 39

With the author's own observations and literature sources as a background the key issues concerned with increasing the viability of the myocardium in acute ischemia are considered. The possibility of a material enlargement of the collateral coronary circulation through administration of mesatonemonoaminoxidase inhibitors, diprazine, preparations of the metabolites type and of other agents is shown. Under consideration are data on the membranes-stabilizing effect in acute ischemia of the myocardium of dimedrol, diprazine and prednisolone, as well as possible ways of increasing the survival of the myocardium by activating the redox-processes and through an adequate supply of energy to ensure the vital functions of the myocardial cell at rest by using pertinent pharmacological agents (cytochrome C, NADP, ubiquinone, hexose-phosphate, monoaminodicarboxylic amino acids).
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PMID:[Problem of increasing the viability of the ischemic myocardium in the light of experimental studies]. 23 63

Some of the barriers to successful lung transplantation include the lack of acceptable methods for ischemic protection and the absence of reliable systems for preservation. The lung response to 60 minutes of warm ischemia basically consists of alveolar-capillary edema and disruption, mitochondria swelling, interstitial hemorrhage, significantly depressed pulmonary function, elevation of pulmonary vascular resistance, and considerable drop in levels of glucose, phospholipids, and adenosine triphosphate. The tolerance to warm ischemia increases to several hours with the use of different systems of ventilatory assistance with or without positive end-expiratory pressure. Several methods of preservation have been attempted: hypothermia, hyperbaria, and hypothermic pulsatile or nonpulsatile perfusion. Hypothermic pulsatile perfusion appears to offer longer periods of protection than the other methods. Longer periods of ischemia and extended preservation may be made possible by advances in the use of drug protection during warm ischemia and the utilization of intracellular colloid or noncolloid solutions for hypothermic storage or hypothermic pulsatile perfusion.
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PMID:Lung preservation techniques. 32 20

The effect of extracellular crystalloid (Ringer's) and colloid (silica gel fraction [SGF]) solutions, and intracellular crystalloid (Sacks) and colloid (modified silica gel fraction [MSGF]) solutions for canine heart preservation in a 24 to 48 hour model of hypothermic storage and zero to 30 minutes of warm ischemia was compared. Canine hearts flushed with an intracellular colloid solution (MSGF) had better survival rates after transplantation than did the hearts flushed with intracellular crystalloid solutions (Sacks). Better survival results also were observed in the group of hearts flushed with extracellular colloid (SGF) solutions than extracellular crystalloid (Ringer's) solutions. The most important theoretical factor in heart preservation appears to be hyperosmolarity and elevated concentration of potassium, proteins, and glucose.
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PMID:Preservation of canine hearts after warm ischemia (zero to thirty minutes) and one to two days of hypothermic storage. A comparative analysis of crystalloid and colloid solutions with different osmolarity and ion composition. 33 90

Canine kidneys (n = 17) were flushed with COLLINS (C2), SACKS II, LAMBOTTE (KMgS), ROSS (hypertonic citrate), or RINGER glucose-mannitol solution following a 30-min period of normothermic ischemia. After 24 h hypothermic preservation with retrograde oxygen persufflation (ROP) and autotransplantation, the immediate functional recovery was determined using inulin and PAH clearance methods and compared with the normal contralateral kidney. While a good functional recovery was found in the COLLINS group, significantly exceeding results from hypothermic ischemic storage preservation, in experiments using other flush solutions ROP preservation resulted in only a small immediate function. Thus the experiments indicate that COLLINS solution C2 is the optimal flush solution for ROP preservation.
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PMID:[Hypothermic storage under aerobic conditions--the effect of different flushing solutions on kidney functional recovery]. 37 90

There are 2 competing methods for cooling the kidney in situ during surgical ischemia: from without by applying ice to the renal surface and from within by perfusing the renal artery. The latter procedure is said to be superior in protecting renal function. Herein the protective effect on renal function of both methods are compared. Pigs of 15--25 kg weight underwent nephrectomy on one side. The remaining kidney was subjected to cold ischemia during 90 minutes while perfusion- or surface cooling was performed. For perfusion cooling the aorta was punctured and the catheter introduced into the renal artery. The perfusing liquid consisted of a physiologic electrolyt solution (Ringer-Lactate) with heparin kept at a temperature of 3--5 degrees C. The initial perfusion lasted 10 minutes and resulted in a median renal core temperature of 23 degrees C. Then the kidney was put on a cooling pad and every 15 minutes again perfused for one minute. For surface cooling sterile melting ice made of glucose solution 5% was applied directly to the kidney. The renal core temperature could be kept at 15--20 degrees C. The two methods of hypothermia were judged by comparing the serum creatinine levels and the I131-hippuran clearances one month after surgery. There was no difference whatever as analysed by the t-test. Hypothermia by applying ice to the renal surface therefore proved to be equivalent to hypothermia by perfusion. Moreover it is much simpler.
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PMID:[Renal hypothermia in situ. Comparison between surface and perfusion cooling concerning renal function in pigs (author's transl)]. 41 41

The conducting system was studied in an in situ perfused swine heart preparation with reduced coronary flow (ischemia) using perfusate containing high and low levels of glucose (26.6 versus 8.6mM) with and without insulin. Coronary flow was maintained at normal levels for 60 minutes in control hearts. In ischemic hearts flow was reduced to about 50 percent of control levels for 30 minutes. Ultrastructural studies documented only subtle modifications of Purkinje fibers in ischemic hearts. Glycogen depletion and disruption of cell junctions were observed in some fibers. One consistent finding was the activation of the lysosomal system. The outer membranes of primary lysosomes appeared herniated and in some cases disrupted, and small vesicles containing hydrolytic enzymes were seen in association with the Golgi apparatus and larger primary lysosomes. Specimens prepared for the demonstration of acid phosphatase indicated a redistribution of hydrolytic enzymes in Purkinje fibers with a depostion of acid hydrolases in smaller lysosomal vesicles, the transverse and side-to-side junctions between cells, and occasionally in the sarcoplasmic reticulum. Enriched perfusate containing high levels of glucose with insulin appeared to have no therapeutic effects in terms of the structure of the Purkinje fibers. The results suggest that alterations in the lysosomal system may be one of the earliest structural changes which occur in oxygen-deficient hearts.
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PMID:Ischemic injury to the conducting system of the heart. Involvement of myocardial lysosomes. 43 Oct 98


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