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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscle acidosis has been implicated as a major determinant of reflex sympathetic activation during exercise. To test this hypothesis we studied sympathetic exercise responses in metabolic myopathies in which muscle acidosis is impaired or augmented during exercise. As an index of reflex sympathetic activation to muscle, microneurographic measurements of muscle sympathetic nerve activity (MSNA) were obtained from the peroneal nerve. MSNA was measured during static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients in whom exercise-induced muscle acidosis is absent (seven myophosphorylase deficient patients; MD [McArdle's disease], and one patient with muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia studied in one McArdle patient, caused sustained elevation of MSNA above basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acidosis is not a prerequisite for sympathetic activation in exercise.
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PMID:Sympathetic activation in exercise is not dependent on muscle acidosis. Direct evidence from studies in metabolic myopathies. 954 95

Psychological factors are known to affect biological processes involved in the progression of coronary artery disease. This article focuses on psychological risk factors for progression of coronary artery disease and its clinical manifestations. Recent research on the adverse cardiovascular consequences of feelings of exhaustion and acute psychological arousal is reviewed, and a classification of psychological risk factors is presented distinguishing (1) chronic psychological risk factors, such as hostility; (2) episodic risk factors, such as exhaustion, with a duration ranging from several months to 2 years; and (3) acute psychological triggers, including mental activity and anger. The distinctive pathophysiological mechanisms by which these psychological risk factors promote coronary disease progression and cardiac ischemia are described, including hemodynamic reactivity, blood clotting, and inflammatory processes.
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PMID:Chronic and acute psychological risk factors for clinical manifestations of coronary artery disease. 1044 56

Gut ischemia-reperfusion injury is a serious condition in intensive care patients. Activation of immune cells within the huge endothelial surface area of gut microcirculation may initiate a systemic inflammatory response with secondary injury to distant organs. Translocation of bacteria and toxins through a leaky gut mucosa may amplify or perpetuate systemic inflammation, leading to multiple organ dysfunction syndrome and death in critically ill patients. Gut ischemia promotes regional production of inflammatory mediators, expression of cell adhesion molecules on endothelial and immune cell surfaces and increases the procoagulatory properties of vascular endothelial cells. During reperfusion, gut injury may be amplified by increased production of oxygen radicals and exhaustion of endogenous antioxidant defence mechanisms. Although several therapeutic strategies to interrupt the pathophysiology of ischemia-reperfusion have been shown to be beneficial in animal experiments, none of these interventions has gained clinical relevance. After initial hemodynamic and respiratory stabilisation of critically ill patients, strategies to prevent secondary gut injury by increasing splanchnic oxygen delivery or augment mucosal cell regeneration may be the only therapeutic options for intensive medical specialists at the present time. Early enteral nutrition and treatment with specific vasoactive drugs may reduce morbidity and costs of treatment in certain critically ill patients. However definitive evidence of a reduction in mortality with these therapies has still not be provided.
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PMID:[Intestinal ischemic reperfusion syndrome: pathophysiology, clinical significance, therapy]. 1046 40

Contrary to common concepts, the brain in Alzheimer's disease (AD) does not follow a suicide but a rescue program. Widely shared features of metabolism in starvation, hibernation and various conditions of energy deprivation, e.g. ischemia, allow the definition of a deprivation syndrome which is a phylogenetically conserved adaptive response to energetic stress. It is characterized by hypometabolism, oxidative stress and adjustments of the glucose-fatty acid cycle. Cumulative evidence suggests that the brain in aging and AD actively adapts to the progressive fuel deprivation. The counterregulatory mechanisms aim to preserve glucose for anabolic needs and promote the oxidative utilization of ketone bodies. The agent mediating the metabolic switch is soluble Abeta which inhibits glucose utilization and stimulates ketone body utilization at various levels. These processes, which are initiated during normal aging, include inhibition of pro-glycolytic neurohormones, cholinergic transmission, and pyruvate dehydrogenase, the key transmitter and effector systems regulating glucose metabolism. Hormonal and effector systems which promote ketone body utilization, such as glucocorticosteroid and galanin activity, GABAergic transmission, nitric oxide, lipid transport, Ca2+ elevation, and ketone body metabolizing enzymes, are enhanced. A multitude of risk factors feed into this pathophysiological cascade at a variety of levels. Taking into account its pleiotropic regulatory actions in the deprivation response, a new name for Abeta is suggested: deprivin. On the other hand, cumulative evidence, taken together compelling, suggests that senile plaques are the dump rather than the driving force of AD. Moreover, the neurotoxic action of fibrillar Abeta is a likely in vitro artifact but does not contribute significantly to the in vivo pathophysiological events. This archaic program, conserved from bacteria to man, aims to ensure the survival of a deprived organism and controls such divergent processes as sporulation, hibernation, aging and aging-related diseases. In contrast to the immature brain, ketone body utilization of the aged brain is no longer sufficient to meet the energetic demands and is later supplemented by lactate, thus recapitulating in reverse order the sequential fuel utilization of the immature brain. The transduction pathways which operate to switch metabolism also convey the programming and balancing of the de-/redifferentiation/apoptosis cell cycle decisions. This encompasses the reiteration of developmental processes such as transcription factor activation, tau hyperphosphorylation, and establishment of growth factor independence by means of Ca2+ set point shift. Thus, the increasing energetic insufficiency results in the progressive centralization of metabolic activity to the neuronal soma, leading to pruning of the axonal/dendritic trees, loss of neuronal polarity, downregulation of neuronal plasticity and, eventually, depending on the Ca2+ -energy-redox homeostasis, degeneration of vulnerable neurons. Finally, it is outlined that genetic (e.g. Down's syndrome, APP and presenilin mutations and apoE4) and environmental risk factors represent progeroid factors which accelerate the aging process and precipitate the manifestation of AD as a progeroid systemic disease. Aging and AD are related to each other by threshold phenomena, corresponding to stage 2, the stage of resistance, and stage 3, exhaustion, of a metabolic stress response.
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PMID:A unifying hypothesis of Alzheimer's disease. IV. Causation and sequence of events. 1106 71

Rat genetic models of intrinsic (i.e., untrained) low-capacity runners (LCR) and high-capacity runners (HCR) are being developed by artificial selective breeding for treadmill running. At generation 3, these lines differed in running capacity by 114%. We used generation 3 rats to test the hypotheses that HCR, relative to LCR, have 1) greater isolated cardiac performance and 2) more resistance to myocardial ischemic insult. The LCR ran for 227 +/- 7 m, and the HCR ran 994 +/- 11 m at exhaustion (337% difference, P < 0.001). Isolated heart performance was assessed from cardiac output (CO) generated at constant preload (15 mmHg) and afterload (70 mmHg) using a Langendorff-Neely working heart preparation. CO averaged 33.5 +/- 2.0 ml. min(-1). g(-1) in LCR hearts and 49.9 +/- 1.4 ml. min(-1). g(-1) in HCR hearts (49% difference, P < 0.001). Recovery of CO after 25 min of global ischemia was not different between the lines. These results suggest that 1) increased cardiac performance accounts for part of the difference in running capacity between the lines; and 2) unlike exercise training, genetically determined intrinsic capacity for exercise does not influence the recovery from 25 min of global low-flow cardiac ischemia.
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PMID:Cardiac function in rats selectively bred for low- and high-capacity running. 1170 62

The transport of sodium and potassium between the intra- and extracellular pools and the maintenance of the transmembrane concentration gradients are important to cell function and integrity. The early disruption of the sodium pump in myocardial infarction in response to the exhaustion of energy reserves following ischemia and reperfusion results in increased intracellular (and thus total) sodium levels. In this study a method for noninvasively quantifying myocardial sodium levels directly from sodium (23Na) MRI is presented. It was used to measure total myocardial sodium on a clinical 1.5T system in six normal dogs and five dogs with experimentally-induced myocardial infarction (MI). The technique was validated by comparing total sodium content measured by 23Na MRI with that measured by atomic absorption spectrophotometry (AAS) in biopsied tissue. Total sodium measured by 23Na MRI was significantly elevated in regions of infarction (81.3 +/- 14.3 mmol/kg wet wt, mean +/- SD) compared to noninfarcted myocardial tissue from both infarcted dogs (36.2 +/- 1.1, P < 0.001) and from normal controls (34.4 +/- 2.8, P < 0.0001). Myocardial tissue sodium content as measured by 23Na MRI did not vary regionally in the lateral, anterior, or inferior regions in normal hearts (ANOVA, P = NS). Sodium content measured by 23Na MRI agreed with the mean AAS estimates of 31.3 +/- 5.6 mmol/kg wet wt (P = NS) in normal hearts, and did not differ significantly from AAS measurements in MI (P = NS). Thus, local tissue sodium levels can be accurately quantified noninvasively using 23Na MRI in normal and acutely reperfused MI. The detection of regional myocardial sodium elevations may help differentiate viable from nonviable, infarcted tissue.
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PMID:Noninvasive quantification of total sodium concentrations in acute reperfused myocardial infarction using 23Na MRI. 1174 81

All the advancements in the understanding of the molecular and cellular processes leading to the great investments in developing neuroprotection against cerebral ischemic/hypoxic damage cannot obscure the simple fact that exhaustion of energy supplies is still at the basis of this disorder. Much has been investigated and postulated over the years about the quick collapse of energy metabolism that follows oxygen and glucose deprivation in the brain. Anaerobic glycolysis, recognized as a pathway of paramount importance in keeping energy supplies, although, at bare minimum, has also presented a dilemma-a significant increase in lactate production during ischemia/hypoxia (IH). The dogma of lactate as a useless end product of anaerobic glycolysis and its postulated role as a detrimental player in the demise of the ischemic cell has persisted for the past quarter of a century. This persistence is due to, at least in part, the well-documented phenomenon termed "the glucose paradox of cerebral ischemia," the unexplained aggravation of postischemic neuronal damage by preischemic hyperglycemia. Recent studies have questioned the deleterious effect of lactic acid, while others even have offered the possibility that this monocarboxylate serves as an aerobic energy substrate during recovery from IH. Reviewed here are studies published over the past few years along with some key older papers on the topic of energy metabolism and recovery of neural tissue from IH. New insights gained from both in vitro and in vivo studies on energy metabolism of the ischemic/hypoxic brain should improve our understanding of this key metabolic process and the chances of protecting this organ from the consequences of energy deprivation.
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PMID:Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. 1191 66

Exercise training for patients with coronary artery disease (CAD) is recommended in a wide range between 40-85% of maximum functional capacity (MFC) or 55-90% of maximum heart rate (HR). During exercise, high levels of catecholamines and metabolic acidosis could induce arrhythmia and ischemia. But catecholamines have never been determined in CAD during constant load exercise in the upper range of recommended intensities. In 11 CAD patients (age 58+/-8 years, BMI 26.1+/-4.0 kg x m(-2), NYHA I n=7, II n=4) we tested the maximum functional capacity (MFC), norepinephrine (NE), epinephrine (E) and blood lactate ([Lac(-)](B)) in a symptom-limited incremental ergometer test. Related to the exercise recommendation, the kinetics of NE, E and [Lac(-)](B) were determined in two 30 min constant load tests in randomized order: one was performed at the anaerobic lactate threshold (CTAT), a second was performed 10% above the individual threshold intensity (CT+10%). In the incremental tests maximum workload and VO(2) were 141+/-54 W and 1766+/-532 ml x min(-1), respectively (85+/-22% of normal; [Lac(-)](B) 5.7+/-1.9 mmol x l(-1), HR 138+/-28 b x min(-1), NE 11.7+/-5.1, E 1.6+/-1.4 nmol x l(-1)). In CTAT the anaerobic threshold (63+/-7% of MFC) represented the mean range of recommended exercise intensity for CAD (40-85%) and could be validated as steady-state intensity because catecholamines and [Lac(-)](B) concentrations remained constant after the initial increase (workload 88+/-35 W, [Lac(-)](B) 3.3+/-1.4 mmol x l(-1), HR 117+/- 23 b x min(-1), NE 8.3+/-3.5, E 0.8+/- 0.7 nmol x l(-1)). In all patients CT+10% (71+/-7% of MFC) led to a continuous rise in [Lac(-)](B), to a NE overload and to earlier exhaustion, although the intensities were in the recommended training range (workload 100+/-38 W, [Lac(-)](B) 5.8+/- 1.9 mmol x l(-1), HR 129+/- 29 b x min(-1), NE 13.9+/-6.9, E 1.5+/- 1.7 nmol x l(-1); p<0.01 against CTAT for all except E). Conclusions In the upper range of recommended training intensity for CAD patients, norepinephrine and lactate were higher during endurance exercise than at MFC in incremental tests. Endurance exercise with intensities >70% of MFC could overload the cardiac patient and increase the risk of arryhthmia and ischemia. Therefore, endurance exercise should be performed below 70% of MFC or below 85% of maximum HR, respectively, whereas higher intensities should apply to interval exercise.
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PMID:[Exercise recommendation and catecholamines in patients with coronary artery disease]. 1244 96

Retinal ischemia is the main chain in the pathogenesis of vascular diseases of the eye. It was established that nitric oxide (NO) plays the key role in the development of ischemia. Recent understanding of the NO role, as a universal regulator of the cellular and tissue metabolism, is presented. The authors' and published data were used to design a scheme of pathogenesis of retinal ischemia with regard for the NO role. NO can produce both positive and negative effects depending on a stage of the process, NO concentration and on a number of other factors if they are present. Initial stages of hypoxia/ischemia are accompanied by an activation of all forms of NO-synthases (NOS) caused by the influence of biologically active substances (cytokines, prostaglandins, serotonin, bradykinin, glycolisis suboxide products etc.). The activation of inducible NOS, which synthesize a bigger quantity of NO possessing a direct cytotoxic action and contributing to the production of highly toxic radical of peroxinitrit, is in the focus of attention. The damage of cellular structures due to free-radical processes leads to the development of endothelial, macrophage and thrombocyte malfunctions, which manifest itself through a reduced activity of endothelial NOS and through disruption of NO-dependent processes (vasospasm, an increased aggregation of platelets and a reduced fibrinolytic activity). A sharp reduction of NO synthesis substrate (L-arginine) is observed in patients with retinal ischemia. The aggravation of ischemia causes a decrease of NO synthesis due to an exhaustion of L-arginine and its intensified consumption in the course of free-radical processes. The use of NO-inhibitors and of NO-donors at different stages of retinal ischemia prevents the development of neovascularization and proliferation.
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PMID:[Retinal ischemia and nitric oxide]. 1280 Apr 88

The mechanism by which inhibition of Na+/H+ exchanger (NHE) reduces cell death in ischemic-reperfused myocardium remains controversial. This study investigated whether cariporide could inhibit mitochondrial NHE during ischemia, delaying H+ gradient dissipation and ATP exhaustion. Mouse cardiac myocytes (HL-1) were submitted to 1 h of simulated ischemia (SI) with NaCN/deoxyglucose (pH 6.4), with or without 7 microM cariporide, and mitochondrial concentration of Ca2+ (Rhod-2), 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and the charge difference across the mitochondrial membrane potential (Deltapsim, JC-1) were assessed. ATP content was measured by bioluminescence and mitochondrial swelling by spectrophotometry in isolated mitochondria. Cariporide significantly attenuated the acidification of the mitochondrial matrix induced by SI without modifying Deltapsim decay, and this effect was associated to a delayed ATP exhaustion and increased mitochondrial Ca2+ load. These effects were reproduced in sarcolemma-permeabilized cells exposed to SI. In these cells, cariporide markedly attenuated the fall in mitochondrial pH induced by removal of Na+ from the medium. In isolated mitochondria, cariporide significantly reduced the rate and magnitude of passive matrix swelling induced by Na+ acetate. In isolated rat hearts submitted to 40-min ischemia at different temperatures (35.5 degrees, 37 degrees, or 38.5 degrees C) pretreatment with cariporide limited ATP depletion during the first 10 min of ischemia and cell death (lactate dehydrogenase release) during reperfusion. These effects were mimicked when a similar ATP preservation was achieved by hypothermia and were abolished when the sparing effect of cariporide on ATP was suppressed by hyperthermia. We conclude that cariporide acts at the mitochondrial level, delaying mitochondrial matrix acidification and delaying ATP exhaustion during ischemia. These effects can contribute to reduce cell death secondary to ischemia-reperfusion.
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PMID:Cariporide preserves mitochondrial proton gradient and delays ATP depletion in cardiomyocytes during ischemic conditions. 1291 86


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