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)

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Mitochondrial inner membrane enzyme defects in porcine myocardial ischemia. 645 Nov 85

We investigated the temporal and spatial development of infarcts in porcine hearts to evaluate the time-dependent beneficial effect of reperfusion on infarct size. The left anterior descending coronary artery (LAD) was occluded in 17 pigs for different periods of time followed by 4 hours of reperfusion. Transmural needle biopsies subdivided into subendocardial and subepicardial halves were taken from the ischemic apex after 60 min of ischemia to determine the tissue concentrations of ATP and NAD. The myocardium-at-risk was assessed with a fluorescent dye injected into the right atrium at the end of the experiments, just after the LAD had been reoccluded. The excised hearts were cut into slices parallel to the heart basis. The ischemic myocardium was measured by planimetry of the non-fluorescent areas whereas the infarcted tissue was determined with the NBT stain and related to the area-at-risk. Ischemic cell death started in the jeopardized left ventricular subendocardial septum after about 30 min of ischemia. The further progress involved the right subendocardial septum and the subendocardium of the left anterior free wall. Already after 75 min of ischemia most of the myocytes-at-risk were irreversibly injured. Infarctions reached their final extent after 90-120 min of ischemia. These results indicate that in hearts without a significant collateral blood flow reperfusion can only reduce infarct size if its initiated within 60-75 min of ischemia. Like in canine hearts infarctions progress from the ischemic subendocardium towards the outer layers.
 ...
PMID:Temporal and spatial development of infarcts in porcine hearts. 648 36

The effects of 3 hours of ischemia and 1 hour of reperfusion on biochemical, physiological and ultrastructural parameters were studied in 12 dogs. In the ischemic subendocardium without reperfusion, mitochondrial losses of adenine (ATP + ADP + AMP) and pyridine (NAD + NADH) nucleotides far exceeded those observed in whole tissue. Adenine nucleotide translocator (ANT) was severely inhibited and seemed to be a sensitive indicator of a lesion of the inner mitochondrial membrane. Postischemic reperfusion led to a slight loss of adenine and pyridine nucleotides from the reversibly damaged subepicardium and to an enormous loss from the irreversibly damaged subendocardium. The washout of nucleotides from irreversibly damaged areas caused the negative para-Nitro Blue Tetrazolium ( pNBT ) staining of the infarcted tissue. Diagnosis of cell death with pNBT failed after the occlusion period without reflow because pyridine, although lost from the mitochondria, was still present in the tissue. In reversibly injured areas, mitochondrial function and ultrastructure were restored after reperfusion, although a significant nucleotide loss was found in the tissue. These studies suggest that mitochondrial ultrastructure and function may play a key role in cellular viability during recovery from ischemia.
 ...
PMID:Mitochondrial damage during myocardial ischemia. 674 90

The temporal relationships among onset of cellular anoxia after coronary artery occlusion, contractile dysfunction, and electrocardiographic ischemia were studied in dogs with an intact circulation. Nicotinamide adenine dinucleotide (NADH) fluorescence was used to detect intracellular anoxia, using a fiber-optic method. Paired NADH concentrations from ischemic (394 +/- 10 mumol/g) and normoxic (285 +/- 11 mumol/g) regions of the heart were obtained, and the differences (delta[NADH]) were correlated with compensated fluorescence (r = 0.76, P less than 0.01). Onset of fluorescence occurred 1 to 2 sec after coronary artery occlusion, followed by hemodynamic (5 sec) and electrocardiographic (13 sec) changes. These data indicate that intracellular anoxia, with alterations in redox potential, is not synchronous with the onset of contractile failure and provide indirect support for intracellular acidosis as the likely mediator of contractile failure.
 ...
PMID:Detection of intracellular anoxia and its relationship to onset of hemodynamic dysfunction and ST-segment elevation in the intact dog heart. 685 70

The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.
 ...
PMID:Effects of ischemia and reperfusion on pyruvate dehydrogenase activity in isolated rat hearts. 687 85

The effects of ischemia on in vivo fatty acid metabolism in fetal lung were studied using rabbit fetuses of 25 to 28 gestational age. Ischemia was produced by inflating the aortic balloon thereby reducing the uterine blood flow. Ischemic insult resulted significant increase in lactate/pyruvate and NADH/NAD ratios and decrease in ATP/ADP ratio in fetal lung. Levels of CoA, acetyl CoA, carnitine and acetyl carnitine decreased while those of long chain acyl CoA and long chain acyl carnitine enhanced. Tissue content of these metabolites returned to normal after 2 hr stabilization following 20 min of ischemic insult. Ischemia also caused small increase in lipogenesis and neutral lipid content of fetal lungs. Our results thus suggest that beta-oxidation in fetal lung is inhibited and becomes rate-limiting for fatty acid oxidation during ischemia. Sudden occurrence of hypoxia or ischemia in the fetus is a typical challenge for the obstetricians. The patients occasionally suffer from neurological injury following cerebral hypoxemia. The hypoxic insult may also affect the respiratory activity significantly. For example, acute alveolar hypoxia causes pulmonary vasoconstriction by damaging pulmonary vascular smooth muscle (1) and results in reduction of fatty acid oxidation by limiting the ATP supply required for metabolic processes (2). Hypoxia has also been shown to decrease the rate of palmitate incorporation into phospholipids (3), inhibit rate of fatty acid synthesis (3) and depress rate of incorporation of fatty acid and phosphatidic acid into lipids (4). Despite the fact that fatty acids represent a major substrate for energy metabolism in lung, no work has been done on the fatty acid metabolism in fetal lung. The present study was designed to determine the fate of fatty acid oxidation in fetal lung during ischemic challenge. The levels of acyl CoA and acylcarnitine intermediates were also measured in order to determine the rate-controlling steps of fatty acid metabolism in the fetal lung.
 ...
PMID:Effect of ischemia on fatty acid metabolism in fetal lung. 688 85


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