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)

During myocardial ischemia high amounts of noradrenaline are released from the sympathetic nerve terminals of the heart and accumulate in the extracellular space of the ischemic area. This increase in local catecholamine concentrations within the still viable myocardium may induce further deterioration of myocardial function during the ischemic process, i.e., acceleration of cell damage and induction of arrhythmias. Three different mechanisms of local catecholamine release have been demonstrated to operate subsequently during the course of myocardial ischemia. Correspondingly, three phases of release must be considered. Phase 1 (ischemia up to 10 min): The release of catecholamines occurs by exocytosis and depends on the activity of the efferent cardiac sympathetic nerves. The extracellular accumulation of noradrenaline is limited by the activity of the neuronal reuptake process and by presynaptic inhibitory effects of adenosine. Phase 2 (10-40 min of ischemia): A massive accumulation of noradrenaline is found in the extracellular space of the ischemic myocardium. The release is determined by local energy exhaustion rather than by centrally originating factors. The release mechanism is different from exocytosis and demonstrates the characteristics of a carrier-mediated efflux using the neuronal uptake carrier in reverse of its normal transport direction. Phase 3 (ischemia longer than 40 min): The release occurs in parallel with the development of structural membrane defects within the ischemic area and the sympathetic neurons progressively deplete from noradrenaline. Among these mechanisms, the carrier-mediated release of noradrenaline appears to be of greatest significance since during Phase 2, extracellular noradrenaline concentrations reach micromolar concentrations capable of producing myocardial necrosis even in the nonischemic heart.
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PMID:Adrenergic mechanisms in myocardial infarction: cardiac and systemic catecholamine release. 246 29

Biochemical, pharmacological, and molecular biological data provide evidence for the presence of a cardiac renin-angiotensin system. Tissue angiotensins were demonstrated in all regions of the mammalian heart. Reduction of cardiac angiotensin II formation after oral administration of converting enzyme (CE) inhibitors in nephrectomized animals points to local generation of these peptides. Functional studies in isolated working rat hearts subjected to transient regional ischemia and reperfusion showed that there is aggravation of arrhythmias as well as exhaustion of energy status by angiotensins. This was prevented by CE inhibition and/or perfusion with bradykinin (BK), which in turn could be competitively antagonized with a BK antagonist. Intracoronary infusion of low-dose bradykinin attenuated ischemia-reperfusion injuries and reduced enzyme and lactate release in anesthetized dogs. Oral pretreatment with the CE inhibitor ramipril in rats, in doses that did not affect the elevation of blood pressure caused by aortic constriction, could prevent induction of as well as cause regression of established cardiac hypertrophy. In contrast, pure vasodilation was without effect on cardiac enlargement despite lowering blood pressure, pointing to a possible trophic influence of angiotensin II. Thus, apart from afterload reduction and euvolumia produced by CE inhibition, the outstanding efficacy of this therapeutic approach in congestive heart failure and cardiac hypertrophy and its potential usefulness in myocardial ischemia may also be explained by intracardiac suppression of angiotensin II generation and bradykinin degradation.
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PMID:Pharmacological interference with the cardiac renin-angiotensin system. 248 22

Predominantly regional disorders of blood aggregation control, aggravating with the progress of ischemia, were detected in patients with obliterating thromboangiitis of the legs. Local overstrain and exhaustion of compensatory anticoagulation and thrombolytic factors developed in the presence of critical ischemia of the limbs and were accompanied by developing regional prethrombotic state. Regional administration (intra-arterial infusions) of anticoagulants and thrombolytic agents appears to be the most justified line of remedial therapy in these patients.
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PMID:[Disorders of the system of regulation of the aggregative status of the blood in patients with thromboangiitis obliterans of the lower extremities]. 273 39

To investigate the presence, mechanism, and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 50 patients underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared to patients without hypertrophic cardiomyopathy, their basal coronary flow, myocardial oxygen consumption, and left ventricular end-diastolic pressure were significantly higher. Further, the 23 patients with basal obstruction to left ventricular outflow had a significantly higher basal great cardiac vein flow and oxygen consumption than the 27 patients without basal obstruction. During pacing to heart rates of 100 and 130 bpm (the anginal threshold for 41 of 50 patients), those with basal obstruction still demonstrated significantly higher coronary flow and oxygen consumption. Most patients, regardless of the presence or absence of obstruction, had metabolic evidence of ischemia, often severe. At a heart rate of 150, most patients with basal obstruction demonstrated an actual decline in coronary flow, which correlated with an increase in left ventricular filling pressures and more severe metabolic evidence of ischemia. In those without obstruction, ischemia occurred at a lower coronary flow, suggesting more impaired coronary flow delivery than those with obstruction. Abnormalities in oxygen extraction were noted in both groups. Thus, obstruction to left ventricular outflow results in higher basal and stress-induced coronary flow and oxygen requirements, related to elevated left ventricular systolic pressures, resulting in rapid exhaustion of coronary flow reserve during stress. Patients without obstruction, with lower left ventricular systolic pressures, may have greater impairment of flow delivery during stress as a cause of myocardial ischemia.
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PMID:Myocardial ischemia in hypertrophic cardiomyopathy. 343 62

To investigate transmural variations in coronary flow reserve, we studied 20 anesthetized dogs with a Gregg cannula in the left main coronary artery. In 11 dogs, radionuclide-labeled microspheres were injected over a range of perfusion pressures in the control state and during maximal coronary vasodilation produced with chromonar or adenosine. In another nine dogs, control, reactive hyperemic, and adenosine-vasodilated flows were compared at the same perfusion pressures. Adenosine dilated vessels more than did reactive hyperemia, which in turn vasodilated more than did hypoperfusion. Adenosine or chromonar vasodilated more than did hypoperfusion alone in all layers of the heart at perfusion pressures as low as 30 mmHg (P less than 0.05). This effect was greatest in the subepicardium and least in the subendocardium and varied with perfusion pressure (P less than 0.05). Subendocardial-to-subepicardial flow ratios declined with diminishing perfusion pressure despite the fact that flow reserve was present in all layers. We conclude that exhaustion of flow reserve is not the mechanism by which subendocardial ischemia occurs.
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PMID:Transmural coronary flow reserve patterns in dogs. 394 28

The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle has been investigated using the needle biopsy technique. Preliminary studies showed that the activity of phosphorylase in vitro was dependent upon the concentration of inorganic phosphate (Pi) used in the assay system. The Km of phosphorylase a for Pi was found to be 26.2 mmol/l, and that of (a+b) (assayed in the presence of saturating AMP) was 6.8 mmol/l. Because of the difference in Km the apparent percentage of a to (a+b) activity varies with the Pi concentration used in the assay system. Phosphorylase a and (a+b) activities were therefore adjusted to saturating Pi concentrations. The ratio of the activities in this case is independent of the Pi concentration and constitutes a minimal estimate of the fraction of phosphorylase molecules in the a form. The fraction of phosphorylase in the a form in resting muscle was as a mean 22%. Despite nearly a quarter of the phosphorylase being in the a form glycogenolytic activity is extremely low. It is proposed that the concentration of Pi at the active site of the enzyme is low compared to the Km for this of either form of the enzyme, and is limiting to activity. A Pi concentration in resting muscle of 1-3 mmol/l was calculated. During epinephrine infusion at rest 90% of the phosphorylase was transformed to the a form but only a moderate increase in the glycogenolytic rate occurred. This rate approximated to 5-10% of the maximum rate of the enzyme (Vmaxa). During prolonged epinephrine infusion the glycogenolytic rate decreased despite the continuance of 90% or more of the phosphorylase in the a form. In contrast to epinephrine infusion prolonged ischemia resulted in a decrease in the mole fraction of phosphorylase a and simultaneously in an increase of the glycogenolytic rate. During isometric and dynamic exercise there was a rapid transformation of phosphorylase b to a paralleled by pronounced increase in the rate of glycogen breakdown. The increased rate of glycogenolysis during isometric exercise was close to the Vmax of phosphorylase a in vivo. When either form of exercise was continued to fatigue/exhaustion, a re-transformation of phosphorylase a to b was observed. During dynamic exercise cAMP in the muscle increased two fold. This increase was blocked by the prior administration of propranolol.+
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PMID:The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle. 613 34

In order to perform intracardiac repair safely during aortic cross clamping, we designed this study to evaluate the protective effect of coenzyme Q10 (CoQ10) on hypertrophied ischemic myocardium from the aspect of energy metabolism. Six to nine months preceding the study, aortic bandings were carried out on 14 puppies to produce left ventricular hypertrophy (LVH). These dogs with LVH were then subjected to total cardiopulmonary bypass and were evenly divided into control and CoQ10-treated groups (10 mg/kg of intravenous administration plus 1 mg/kg per hr of intracoronary injection). Myocardial ischemia was induced by aortic cross clamping for 2 hr under moderate systemic hypothermia. The results indicated that the administration of CoQ10 had a protective effect on hypertrophied ischemic myocardium, since depletion of high-energy phosphate (HEP) was uniformly prevented, and accumulation of lactate was simultaneously decreased during the 2 hr of aortic cross clamping. On the other hand, there were marked exhaustion of HEP and rapid increase in lactate following the 2 hr of ischemia in the control group, these being much more predominant in the subendocardial layer.
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PMID:Effect of coenzyme Q10 on hypertrophied ischemic myocardium during aortic cross clamping for 2 hr, from the aspect of energy metabolism. 622 44

This prospective study depicts quantitative histophotometric characteristics of the changes in the histoenzymologic spectrum of the liver in the course of temporary ischemia of the extremities with subsequent revascularization. The increase in the activities of dehydrogenases under study in the course of a 3-hour ischemia, and the decrease of these parameters in 6- and 12-hour ischemia was discovered, that was determined as a compensatory response followed by the period of compensation exhaustion and the development of the period of complete exhaustion. The data of the study of drug correction of the postischemia syndrome confirmed the rationality of the efforts that were made. A special program developed for computer processing of histological data allows rapid adaptation of the methods for different histophotometric examinations with the use of TV analyzer of the picture, this creating wider possibilities as compared to the known analogs.
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PMID:[Quantitative histophotometric study of liver dehydrogenase activity during temporary ischemia of the extremities]. 661 43

The present study was carried out on male rats, using three models of experimental hypertension: cerebroischemic, single clamp bilateral and combined, induced by ischemia of the brain and one of the kidneys. The authors determined DA, NA, A in the hypothalamus and medulla oblongata as well as A, NA in plasma in view of the connection between CA (catecholamine) and cerebral and renal renin-angiotensin system (RAS). In rats with cerebral hypertension there was activation of noradrenergic neurons in the hypothalamus and medulla oblongata. There were no changes in the content of A. In rats with renal hypertension the activation of noradrenergic neurons in the hypothalamus was due to exhaustion of NA stores with normal amount of DA, but still the adrenergic neurons were activated. In rats with combined hypertension there was lowering of NA and DA in the hypothalamus, but A was not altered, e.g. the changes, observed singly and in cerebral and renal hypertension were combined. In the three forms of hypertension there were similar changes in medulla oblongata (reduced DA, increased NA and unaltered) and in plasma (A without significant changes). The changes in the level of CA in cerebral and combined hypertension could be explained by a change in the sinocarotid reflex, but in the renal-with the increased level of plasma angiotensin. The authors suggest that the connection between cerebral CA and cerebral RAS is not a direct one and RAS is not directly involved in the inverse interrelationships between cerebral and renal RAS.
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PMID:[Central and peripheral catecholamines in combined cerebral and renal hypertension]. 701 87

The effects of upper and lower body exercise on blood supply to the lower extremities were investigated in patients with peripheral arterial occlusive disease (PAOD) by measurements of transcutaneous oxygen tension (tcPO2) and Doppler ankle pressure (DAP). Twenty patients with PAOD (PAOD group) and 10 subjects without PAOD (control group) performed treadmill test (TT), recumbent cycle ergometry (CE), and rowing ergometry (RE) with a fixed seat. The tcPO2 was registered on the calf and DAP was measured at the end of each step of CE and RE. The walking distance in TT of the control group was not limited (> 1000 m), whereas that of the PAOD group was 161 m in median. In the control group there was no significant difference of performance between CE (125 +/- 33 W) and RE (111 +/- 24 W), whereas in the PAOD group, performance was lower in CE (72 +/- 31 W) than in RE (102 +/- 28 W) (P < 0.01). DAP of controls increased during both CE (136 to 165 mmHg) and RE (170 to 213 mmHg), whereas the DAP of the PAOD group decreased during CE (from 85 to 44 mmHg) and remained relatively constant during RE (113 to 101 mmHg). In controls, tcPO2 did not distinctly change during TT (70 to 66 mmHg) and increased during CE (58 to 73 mmHg) and RE (69 to 82 mmHg), whereas in the PAOD group, tcPO2 decreased during TT (66 to 33 mmHg) and CE (50 to 22 mmHg) and remained almost unchanged in RE (64 to 60 mmHg). A hyperbolic relationship was found between tcPO2 and DAP. In conclusion, during upper body exercise, blood supply to the lower extremities in patients with PAOD was not affected, whereas lower body exercise led to exhaustion of the functional reserve of blood supply. Because of a hyperbolic relationship between tcPO2 and DAP, tcPO2 remained relatively constant if blood supply was sufficient, but in disturbed blood supply a small change of DAP was accompanied by a great change of tcPO2. Therefore, in critical ischemia the change of tcPO2 was more sensitive than that of DAP.
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PMID:Transcutaneous oxygen tension and Doppler ankle pressure during upper and lower body exercise in patients with peripheral arterial occlusive disease. 763 15


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