Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelium is critically involved in the regulation of vascular function through its barrier role, via interaction with circulating cells such as platelets, which then release vasoactive or growth regulating agents, through production of substances which may modulate vascular tone and smooth muscle cell growth and also exert anti-thrombotic effects. The release of serotonin, adenosine diphosphate (ADP), or growth factors from platelets adhering to damaged endothelium, the release of endothelium-derived relaxing or contracting factors (nitric oxide, prostanoids, endothelin), the production of growth factors, all of which exert their effects in paracrine or even autocrine fashion, are some of the mechanisms whereby the endothelium influences vascular tone and growth and platelet aggregation. In different conditions such as hypertension, atherosclerosis, diabetes, heart failure, ischemic heart disease, sepsis, and shock, dysfunction of the endothelium plays an important pathophysiological role through reduction or enhancement of the release of these different products with significant hemodynamic and trophic effects. Therapeutic interventions targeting the endothelium hold promise in the treatment and prevention of some cardiovascular diseases and their complications.
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PMID:The endothelium and control of blood vessel function in health and disease. 789 24

Functional platelet characteristics were studied in hypertensive subjects having episodes of silent myocardial ischemia. A total of 36 patients with essential hypertension (EH) stage II (WHO criteria, 1979) underwent echocardiography and 24-h ECG monitoring. Platelet aggregation induced by adenosine diphosphate was assessed by laser aggregation analyzer. It is demonstrated that platelet aggregation in EH patients with silent ischemia was increased 5-fold as compared to healthy subjects and 2-fold versus EH patients without ischemia. No significant differences existed between the two groups by such parameters as systolic or diastolic pressure and left ventricular myocardial mass. An involvement of elevated platelet aggregation can be suggested in the genesis of coronary insufficiency in EH associated with episodes of silent myocardial ischemia.
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PMID:[The functional characteristics of the thrombocytes in patients with hypertension and "silent" myocardial ischemia]. 790 27

The endothelium has profound potential to modulate coronary arteriolar tone under a variety of physiological and pathophysiological situations. The endothelium in coronary microvessels is responsible for producing flow-dependent vasodilation, which is mediated by nitric oxide. The endothelium, however, does not mediate the myogenic response of coronary arterioles, but production of nitric oxide nevertheless modulates myogenic responses. The endothelium also has a role in coronary alpha-adrenergic vasoconstriction, because inhibition of nitric oxide synthesis augments coronary alpha 1 and alpha 2-adrenergic vasoconstriction. Other neurohumoral substances or autocoids also have their vasodilator actions mediated through the production of nitric oxide in coronary arterioles. Specifically, serotonin, adenosine diphosphate, and histamine all have their actions transduced through the production of nitric oxide. In the pathophysiological setting with impaired endothelial function, vasodilator responses to endothelium-dependent factors are significantly attenuated, and this can be reversed by administration of L-arginine. These impaired responses may contribute to the pathogenesis of ischaemic heart disease, especially that which occurs due to microvascular spasm.
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PMID:Endothelial regulation of coronary microvascular tone under physiological and pathophysiological conditions. 790 42

Depending on its duration, temporary myocardial ischemia leads to a disturbance of myocardial function before irreversible cellular necrosis is developed. Mechanical, electrical, and metabolic disturbances were suggested to be possible mechanisms accounting for the altered mechanical performance in ischemic hearts. To further investigate the alteration of myocardial energy metabolism on the subcellular level, we determined, by means of nonaqueous fractionation, the cytosolic-mitochondrial distribution of high-energy phosphates and other metabolites (ATP, ADP, phosphocreatine, creatine, and inorganic phosphate) in ischemic (zero-flow) guinea pig hearts after isolated perfused working heart preparation. Additional experiments using 31P nuclear magnetic resonance spectroscopy were performed to determine pHi and [Mg2+]i changes during global ischemia. The total ATP content of myocardial tissue dropped only slowly to 76% of control ATP at 10 minutes and to 51% at 30 minutes and reached almost zero at 60 minutes of ischemia. However, striking differences were observed on the subcellular level: While cytosolic phosphocreatine was almost completely consumed after 3 minutes of ischemia (from 19.1 +/- 1.6 to 3.3 +/- 0.5 mmol/L), ATP concentration in the cytosol decreased within 30 minutes from 8.4 +/- 0.6 to only 5.4 +/- 0.9 mmol/L. Mitochondrial ATP was rapidly and linearly reduced to 60% after 5 minutes of ischemia and was nearly unmeasurable after a further 20 minutes. Thus, in contrast to the breakdown of phosphocreatine in cytosol, the only slight alteration of cytosolic ATP reveals a reduction in cytosolic ATP utilization. Moreover, the unaffected cytosolic-mitochondrial difference in the phosphorylation potential of ATP demonstrates the intact function of the ADP/ATP carrier during early ischemia. These results might indicate a disturbance of the functional coupling between carrier and phosphocreatine kinase (phosphocreatine shuttle), which could be of importance for the early contractile failure in myocardial ischemia.
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PMID:Alteration of the cytosolic-mitochondrial distribution of high-energy phosphates during global myocardial ischemia may contribute to early contractile failure. 792 21

This study was done to determine whether abnormal receptor-dependent release of endothelium-derived relaxing factor (EDRF) might be caused by G-protein dysfunction. Dogs were exposed to global myocardial ischemia (45 minutes, induced by aortic cross-clamping) followed by reperfusion (60 minutes) while on cardiopulmonary bypass, and coronary arteries were then studied in vitro in organ chamber experiments. After reperfusion, endothelium-dependent relaxation to the receptor-dependent agonists adenosine diphosphate and acetyl-choline was significantly impaired as well as to sodium fluoride, which acts on a pertussis toxin-sensitive G-protein. In contrast, endothelium-dependent relaxations to the receptor-independent agonists A23187 and phospholipase C were normal. Furthermore, endothelium-dependent relaxation to poly-L-arginine (molecular weight, 139,200), which appears to induce endothelium-dependent relaxation of the canine coronary artery by a nonnitric oxide pathway, was unaffected by ischemia and reperfusion. These experiments suggest that global myocardial ischemia and reperfusion selectively impair receptor-mediated release of EDRF (nitric oxide) but that the ability of the endothelial cell to produce EDRF or generate endothelium-dependent relaxation to nonnitric oxide-dependent agonists remains intact. We hypothesize that coronary reperfusion injury leads to G-protein dysfunction in the endothelium.
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PMID:Impaired endothelium-dependent relaxation after coronary reperfusion injury: evidence for G-protein dysfunction. 801 Aug 1

Thirty-seven men with angiography or ultrasound confirmed peripheral arterial occlusive disease were divided into two groups. Group 1 included 24 patients treated with one daily infusion of 10 g of phosphocreatine in 200 ml of solvent for 10 days. Group 2 included 13 patients who were given 0.9% NaCl in the same scheme. Groups were comparable in: duration of intermittent claudication, maximal walking distance, Ketle index, cholesterol, triglycerides, frequency of ischemic heart disease, hypertension, diabetes, smoking. Patients were examined 4 times: before starting, on second day, after treatment period, and 1 month after. Treadmill-test; ADP-, PAF-, 5-HT-induced platelet aggregation; D-dimer; PAI-1 activity; blood viscosity at high and low shear rate; hematocrit were performed. After treatment maximal walking distance significantly increased in patients of Group 1. Mechanisms of this effects include positive influence of phosphocreatine on platelet aggregation, blood rheology, coagulation and fibrinolytic systems.
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PMID:The effect of exogenous phosphocreatine on maximal walking distance, blood rheology, platelet aggregation, and fibrinolysis in patients with intermittent claudication. 807

Myocardial ischemia is characterized by a decrease in phosphocreatine (PCr) and Mg(2+)-ATP contents as well as an accumulation of myosin ATPase reaction products (inorganic phosphate [P(i)], protons, and Mg(2+)-ADP). The possibility that these metabolites play a role in rigor tension development was checked in rat ventricular Triton X-100-skinned fibers. Rigor tension was induced by stepwise decreasing [Mg(2+)-ATP] in the presence or in the absence of 12 mmol/L PCr. To mimic the diastolic ionic environment of the myofibrils, [free Ca2+] was set at 100 nmol/L (pCa 7); [free Mg2+], at 1 mmol/L; and ionic strength, at 160 mmol/L. In control conditions (pH 7.1, with no added P(i) or Mg(2+)-ADP), the pMg(2+)-ATP for half-maximal rigor tension (pMg(2+)-ATP50) was 5.07 +/- 0.03 in the presence of PCr. After withdrawal of PCr, the pMg2+)-ATP50 value was shifted toward higher Mg(2+)-ATP values (3.57 +/- 0.03). Addition of 20 mmol/L P(i) shifted the pMg(2+)-ATP50 to 3.71 +/- 0.04 (P < .05) in the absence of PCr and in the opposite direction to 4.98 +/- 0.02 (P < .01) in the presence of PCr. Acidic pH (6.6) strongly increased pMg(2+)-ATP50 in both the absence (3.90 +/- 0.03, P < .001) and presence (5.44 +/- 0.02, P < .001) of PCr. Conversely, Mg(2+)-ADP (250 mumol/L) decreased pMg(2+)-ATP50 to 3.26 +/- 0.06 (P < .001) in the absence of PCr; at pMg(2+)-ATP 4, no rigor tension was observed until PCr concentration was decreased to < 2 mmol/L. At acidic pH, maximal rigor tension was lower by 29% compared with control conditions, whereas in the presence of Mg(2+)-ADP, maximal rigor tension developed to 143% of the control value; P(i) had no effect. The tension-to-stiffness (measured by the quick length-change technique) ratio was lower in rigor (no PCr and pMg(2+)-ATP 6) than during Ca2+ activation in the presence of both PCr and ATP. Compared with control rigor conditions, this parameter was unchanged by Mg(2+)-ADP and decreased by acidic pH, suggesting a proton-induced decrease in the amount of force per crossbridge. In addition to their known effects on active tension, Mg(2+)-ADP and protons affect rigor tension and influence ischemic contracture development. It is concluded that ischemic contracture and increased myocardial stiffness may be mediated by a decreased PCr and local Mg(2+)-ADP accumulation. This emphasizes the importance of myofibrillar creatine kinase activity in preventing ischemic contracture.
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PMID:Myocardial ischemic contracture. Metabolites affect rigor tension development and stiffness. 815 39

Activation of ATP-sensitive K+ (KATP) channels has been implicated as a cause of increased cellular K+ efflux and action potential duration (APD) shortening during myocardial ischemia, hypoxia, and selective glycolytic inhibition, since selective KATP channel antagonists partially or completely block increased cellular K+ efflux and APD shortening under these conditions. During substrate-free hypoxia or myocardial ischemia in intact rabbit ventricle, unidirectional K+ efflux rate during systole approximately doubled and APD decreased by approximately 40% after 10 minutes. In patch-clamped guinea pig ventricular myocytes, similar changes could be produced by activation of < 0.5% of the maximal KATP channel conductance. Furthermore, from studying the desensitizing effects of ADPi on the ATP sensitivity of KATP channels in excised inside-out patches, it was estimated that the rapid changes in the cytosolic ATP/ADP ratio during ischemia and hypoxia were of sufficient magnitude to activate KATP channels to this degree. During selective glycolytic inhibition, however, the global cytosolic ATP/ADP ratio in intact heart remained normal despite an increase in cellular K+ efflux comparable to ischemia and hypoxia. In patch-clamped saponin-permeabilized ventricular myocytes, KATP channels were preferentially suppressed by glycolytic ATP production compared to ATP generated by mitochondria or by the creatinine kinase reaction, and functional glycolytic enzymes were found to be associated with KATP channels in excised membrane patches. We hypothesize that sarcolemma-associated glycolytic enzymes may be important in maintaining a high local cytosolic ATP/ADP ratio in the vicinity of KATP channels, where sarcolemmal ATPases are tending to depress the local ATP/ADP ratio.
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PMID:Metabolic regulation of cardiac ATP-sensitive K+ channels. 825 19

During acute myocardial ischemia, passage of potassium ions across the sarcolemma to the extracellular space is a well-established phenomenon. A recent hypothesis is that the ATP-dependent potassium channel plays a role in contributing to the potassium loss. As the potassium loss starts while the overall level of ATP is still relatively high, and as the channel is inhibited by rather low concentrations of ATP, the question arises as to how the channel is opened. Among the proposals are that, in addition to the total concentration of ATP, there is modulation of the regulation by its breakdown products, such as ADP and adenosine. Alternatively, or in addition, breakdown products of anaerobic glycolysis, such as lactate and protons, may also play a role. Extracellular acidosis may help to activate the channel, and internal lactate accumulation may have a similar effect. In certain circumstances there is evidence that ATP produced by glycolysis plays a significant role in the control of potassium channel activity. The concept of subsarcolemmal ATP is another explanation for the activation of the channel at relatively high ATP concentrations. Potassium channel closing drugs, such as glibenclamide, may prolong the action potential duration (shortened by ischemia) and thereby decrease the incidence of early ventricular arrhythmias. This same category of drugs may reduce early potassium loss from the ischemic tissue, thereby lessening the potentially protective effect of the external accumulation of potassium on the ischemic zone, the so-called local cardioplegic effect. Conversely, drugs of the potassium channel activating group are likely to have opposite effects on these arrhythmias and on myocardial protection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of ischemia by regulation of the ATP-sensitive potassium channel. 825 20

Continuous retrograde warm blood cardioplegia was compared with two widely used hypothermic myocardial protection techniques in a canine model of acute regional myocardial ischemia with subsequent revascularization. Animals (n = 30) underwent 45 minutes of left anterior descending coronary artery occlusion then cardioplegic arrest (60 minutes), followed by separation from cardiopulmonary bypass and data collection. The cold oxygenated crystalloid cardioplegia group (CC; n = 8) and the cold blood cardioplegia group (CC; n = 10) had cardiopulmonary bypass at 28 degrees C, antegrade arrest, and intermittent retrograde delivery. The warm blood cardioplegia group (WB; n = 12) had normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde delivery. Overall ventricular function (preload recruitable stroke work relationship; ergs x 10(3)/mL) was significantly (p < 0.001) better for WB (WB, 80 +/- 11; CB, 67 +/- 13; CC, 57 +/- 12). Systolic function (maximum elastance relationship; mm Hg/mL) was also significantly (p < 0.001) better for WB (WB, 11.6 +/- 3.6; CB, 8.6 +/- 2.7; CC, 6.2 +/- 1.3). Diastolic function (stress-strain relationship; dynes x 10(3)/cm2) revealed significantly (p < 0.001) decreased compliance for CC (WB, 20 +/- 6; CB, 19 +/- 7; CC, 27 +/- 11). Left anterior descending coronary artery regional adenosine triphosphate/adenosine diphosphate ratios were significantly (p = 0.02) worse for CC (WB, 10.2 +/- 2.3; CB, 9.4 +/- 2.6; CC, 5.6 +/- 1.5). Myocardial edema significantly (p = 0.03) increased over time only in the CC animals (WB, 0.4% +/- 2.3%; CB, -0.3% +/- 3.6%; CC, 5.5% +/- 2.3%). In this model of acute regional myocardial ischemia and revascularization, continuous retrograde warm aerobic blood cardioplegia provided superior myocardial protection compared with cold oxygenated crystalloid cardioplegia with intermediate results for cold blood cardioplegia.
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PMID:Revascularization for acute regional infarct: superior protection with warm blood cardioplegia. 826 18


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