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)

The loss of nucleotide pool precursors from the heart during ischemia and reperfusion may affect resynthesis of ATP and consequently mechanical recovery. Isolated working rat hearts were made globally ischemic for from 15 to 25 min, and the tissue content of adenine pool metabolites, creatine, creatine phosphate (CP), and inorganic phosphate (Pi), were measured after 20 min of reperfusion. In addition, the coronary effluent was assayed for nucleotides, nucleosides, and oxypurines. Hearts that recovered 75% or more of their preischemic hemodynamic function had significantly lower ATP and NAD but greater CP and Pi than controls. Complete failure of hearts was associated with severely depleted ATP but not CP. All hearts released 25% or more of their preischemic adenine pool during the 20-min reperfusion. This loss correlated more closely with a reduction in recovery from 100 to 75% than with complete failure. Thus extensive loss of adenine pool precursors is not critically related to the failure of heart muscle to recover function but may be an important limiting factor in determining the extent and time course of mechanical recovery.
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PMID:Myocardial adenine pool depletion and recovery of mechanical function following ischemia. 399 4

Two mitochondrial subpopulations were isolated from guinea-pig heart by density gradient centrifugation. Under control conditions, both contain functionally intact mitochondria in which ischemic damage develops similarly. However, in one subpopulation adenine nucleotide content, adenine nucleotide translocase activity, oxidative phosphorylation and Ca2+ uptake are a quarter lower than in the other one when related to mitochondrial protein mass. Cytochrome contents and uncoupled electron flux are the same. Changes develop most evidently at the very beginning of ischemia for NAD-linked respiration. When ischemia progresses, cytochromes and the translocator protein are gradually lost or inactivated. Thereupon only partial recovery of mitochondrial function can be obtained after 20 min of reperfusion.
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PMID:Development of ischemia-induced damage in defined mitochondrial subpopulations. 404 49

Histochemical study of enzymatic activity in the myocardium was performed in sudden cardiac death. Human hearts in which there were no macroscopic and histological focal or diffuse changes served as material. The following enzymes were studied in the anterior or posterior walls of the left ventricle or in the interventricular septum: succinate dehydrogenase, lactate dehydrogenase (LDH), beta-hydroxybutyrate dehydrogenase (OHBDH), alpha-glycerophosphate- and glucose-6-phosphate dehydrogenase, NAD-diaphorase and phosphorylase. Increased activity of OHBDH and LDH was found: 36,0 and 22,6% higher than in trauma and brain hemorrhage that served as control. These alterations seem to be connected with the increase of blood content of fatty acids, and lactate as a response to the catecholamine excess. Foci of an acute ischemia were found in the interventricular septum in 80% of cases in which phosphorylase was revealed. The appearance of the ischemic foci was obviously due to the coronary arteries contraction.
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PMID:[Histoenzymological characteristics of the myocardium in sudden cardiac death]. 405 12

We investigated if the loss of nicotinamide coenzymes in ischemic-infarcted myocardium may be responsible for the transition from reversibly ischemic to irreversibly infarcted cell damage. The LAD was occluded in 6 dogs for 4 h. Transmural needle biopsies were taken from he ischemic-infarcted region after 1/2, 1, 11/2, 2, and 4 h of ischemia and further divided into subepicardial and subendocardial halves. At each time interval the concentration of the nicotinamide coenzymes NAD, NADH, and NADPH were measured, and the degree of cellular injury was evaluated by electron microscopy. The glycohydrolase activity (EC 3.2.2.5), the enzyme which splits NAD, was determined in brain, myocardium, kidney, and skeletal muscle of 4 rats. Total NAD, the sum of NAD and NADH, started to decrease significantly in the ischemic subendocardium 1 h after onset of ischemia. Degradation of NADPH occurred later. Loss ot total NAD was about 60-70% when electron microscopy diagnosed irreversible cell injury. The glycohydrolase activity was the highest in brain followed by myocardium, kidney, and skeletal muscle, reflecting the different tolerances of these tissues towards ischemia. The key mechanism for ischemic injury seems to be the tissue acidosis which activates the glycohydrolase leading to a loss of the vital coenzymes.
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PMID:Loss of canine myocardial nicotinamide adenine dinucleotides determines the transition from reversible to irreversible ischemic damage of myocardial cells. 627 93

Ischemic myocardium was produced by occluding the left circumflex coronary artery in anesthetized dogs. Autolyzed myocardium was produced by incubating transmural samples of canine left ventricle at 37 degrees C. Tissue pH was recorded continuously in each model using a microcombination pH electrode impaled into the midmyocardium. The activities of the five mitochondrial inner membrane enzyme complexes of electron transport and coupled oxidative phosphorylation were assayed as a function of time of ischemia or autolysis. While the activities of complex II (succinate-CoQ reductase) and IV (cytochrome c oxidase) were completely stable, that of complex I (NADH-CoQ reductase) decreased markedly, but largely only after 20 min of ischemia or autolysis. At 20 min and beyond, the decrease in the activity of complex I paralleled closely the decrease in whole mitochondrial oxygen uptake with NAD-linked substrates in both models. The activity of complex III (CoQH2-c reductase) decreased at a more gradual rate during ischemia or autolysis, and its rate of decrease paralleled that of succinate-supported oxygen uptake. The activity of complex V (oligomycin-sensitive ATPase) decreased most rapidly (by 40% in only 5 min of autolysis) but nearly leveled off beyond 20 min in the two models. A strikingly similar pattern of differential enzyme lability was observed in isolated control mitochondria incubated at lowered pH values. The results demonstrate 1) differential enzyme lability within the mitochondrial inner membrane, 2) a connection between severity of acidosis and the degree of enzyme activity loss, and 3) the usefulness of simple tissue autolysis as an analogue of in situ myocardial ischemia.
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PMID:Mitochondrial complexes I, II, III, IV, and V in myocardial ischemia and autolysis. 630 12

Effect of ischemia and cytochrome c on oxidation of pyruvate and malate as well as of 3-hydroxybutyrate, succinate and exogenous NADH was studied. Respiration of mitochondria at the state 3 was markedly decreased in presence of the mixtures free of cytochrome c and containing pyruvate and malate, 3-hydroxybutyrate and succinate. In the same mixtures, but containing cytochrome c, oxidation of NAD-dependent substrates was decreased less distinctly and oxidation of succinate was similar to the control values. The rate of rhothenone-sensitive oxidation of NADH as well as the activating effect of cytochrome c on oxidation of all the substrates studied, except of NADH, were increased in ischemia. The data obtained suggest that alterations in the mitochondria functional activity in ischemia occur due to an increase in penetration of pyridine nucleotides across the inner membrane and of cytochrome c across the outer layer. Heterogeneity of mitochondria is discussed.
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PMID:[Effect of ischemia on the functional activity and membrane permeability of heart mitochondria]. 633 Oct 1

Mechanisms are described that are known to prolong survival of ischemic myocardium. Some of these mechanisms are species-specific: collateral blood flow does not contribute to survival in rats, rabbits, and pigs but it salvages subepicardial myocardium in the dog and probably in man. The most important defense mechanism is enlargement of collaterals by growth of pre-existing smaller vessels. This process is not operative in sudden coronary occlusion but may save a substantial portion of the myocardium if occlusion occurs more slowly, i.e. several days up to a week. Experimental evidence is presented that thrombotic occlusion, clot-retraction, and partial clot lysis by endothelium can be sufficiently dynamic to allow intermittent myocardial perfusion and to permit collaterals to grow. The glycogen stores of the heart are of limited importance. They are useful for glycolytic ATP-production, the limitation is imposed by the inhibition of glycolysis in ischemia due to unfavourable pH and lack of NAD. Some beta-blockers do interfere with glycogenolysis in the heart. The cardioprotective role of adenosine needs further study. An interesting concept is the change in resistance to ischemia after repeated cycles of ischemia. It is not known at present whether repeated cycles will increase or decrease the myocyte's resistance against ischemia.
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PMID:Natural defense mechanisms during ischemia. 635 74

Using a canine model of subcoronary valvular aortic stenosis, we determined myocardial blood flow, high-energy phosphate content, and mitochondrial function in eight hearts with chronic left ventricular hypertrophy. Fourteen normal hearts were used for control data. Myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, left ventricular transmural biopsy specimens were taken for metabolic analyses. Subepicardial and subendocardial content of adenosine triphosphate (ATP) and creatine phosphate (CP) were assayed. Respiratory control indices for isolated mitochondria were measured by use of NAD-linked and FAD-linked substrates. Endocardial blood flow, subendocardial high-energy phosphate content, and respiratory control indices for NAD-linked substrate in the hearts with chronic left ventricular hypertrophy were significantly lower than the normal values. These data provide insight into the metabolic and myocardial blood flow abnormalities occurring in cardiac hypertrophy and provide a framework for understanding the altered response of hypertrophied hearts to ischemia.
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PMID:Characteristics of chronic left ventricular hypertrophy induced by subcoronary valvular aortic stenosis. I. Myocardial blood flow and metabolism. 645 Aug 57

The increased susceptibility of hearts with chronic left ventricular hypertrophy (CLVH) to damage during ischemia has been suggested but not documented. The purpose of this study was to isolate ischemic events in hearts with CLVH from reperfusion events. Using physiological and biochemical parameters, we compared the rate and extent of myocardial injury during ischemic contracture between eight canine hearts with CLVH induced by subcoronary valvular aortic stenosis and 14 normal canine hearts. Preischemic myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, each heart was instrumented with a left ventricular balloon and made globally ischemic. At control, contracture initiation, and contracture completion left ventricular transmural biopsy specimens were assayed for subepicardial and subendocardial adenosine triphosphate (ATP) and creatine phosphate (CP). Mitochondrial respiratory control indices for NAD-linked and FAD-linked substrates were measured. Preischemic endocardial blood flow in hearts with CLVH was significantly lower than in normal hearts. At control, subendocardial ATP and CP and the respiratory control index for NAD-linked substrate were significantly lower in hearts with CLVH than in normal hearts. Hearts with CLVH reached contracture initiation significantly sooner than normal hearts. All hearts demonstrated significant decreases in high-energy phosphate content and mitochondrial function during ischemia. Reperfusion injury notwithstanding, we concluded that hearts wih CLVH are more susceptible to ischemic injury than are normal hearts, perhaps related to lower endocardial blood flow, lower subendocardial high-energy phosphate stores, and depressed mitochondrial function prior to ischemia.
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PMID:Characteristics of chronic left ventricular hypertrophy induced by subcoronary valvular aortic stenosis. II. Response to ischemia. 645 Aug 58

Left anterior descending coronary artery occlusion in anesthetized pigs produced a stable transmural ischemia characterized by a rapid and then sustained loss of blood flow and mechanical function. After 2 h of occlusion, mitochondria from the ischemic area exhibited a 36 +/- 6% drop in state 3 respiratory activity (QO2) supported by the NAD-linked substrates, glutamate plus malate, but only a 5 +/- 3% decrease in QO2 with succinate plus rotenone. The activity of electron transfer complex I (NADH-CoQ reductase) decreased commensurately by 33 +/- 4% with the decrease in QO2 with NAD-linked substrates. Consistent with the nearly unchanged QO2 with succinate plus rotenone, the activities of electron transfer complexes III and IV decreased only slightly by 9 +/- 5% and 9 +/- 4%, respectively. Mitochondrial ATPase (complex V) activity decreased by 48 +/- 2% with little change in its oligomycin sensitivity. A 48% drop in ATPase activity was shown, by means of oligomycin titrations, to correspond to a 32% decrease in NAD-linked substrate supported QO2. The decreases observed in NADH-CoQ reductase and ATPase activities each account nearly quantitatively for the impaired mitochondrial phosphorylating respiration observed during sustained myocardial ischemia. These results suggest that mitochondrial inner enzyme complexes I and V are important sites of cellular injury in myocardial ischemia.
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PMID:Mitochondrial inner membrane enzyme defects in porcine myocardial ischemia. 645 Nov 85


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