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 effect of acids on activity of afferent sympathetic nerve fibers from the left ventricle has been examined. Action potentials were derived from the upper thoracic communicating rami of the left side of anesthetized dogs. Application of a solution of lactic acid to the left ventricular surface caused excitation in both myelinated and unmyelinated fibers. The minimum concentration required for excitation was 7.5-75 mug/ml for the unmyelinated fibers and 375-750 mug/ml for the myelinated fibers. Excitation of the unmyelinated fibers induced by coronary occlusion was suppressed by pretreatment with sodium bicarbonate, 500 mg/kg. However, excitation of the myelinated fibers was influenced little by the agent. Pretreatment with a large dose of Trasylol failed to suppress excitation induced by coronary occlusion. The result suggests that acidosis plays a role in excitation of the unmyelinated fibers induced by myocardial ischemia, but not in excitation of the myelinated fibers.
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PMID:Acid-induced excitation of afferent cardiac sympathetic nerve fibers. 108 16

Impaired metabolism interferes with the active extrusion of intracellular sodium and results in intracellular edema. In the brain and regionally in the kidney, elevation of extracellular osmolality is accompanied by a reduction of ischemic cell swelling and improvement of reflow of blood after arterial occlusion. Studies were therefore performed to examine the effect of elevation of extracellular osmolality on ischemic myocardial physiology and by morphologic examination on the extent of acute injury and subsequent necrosis. Under conditions of controlled hemodynamics, administration of hyperosmotic mannitol resulted in improvement of function of the canine heart with regional ischemia, a lessening of the extent of ischemic injury assessed by electrocardiographic ST segment mapping, and improved total and collateral blood flow. Metabolic studies under conditions of controlled hemodynamics revealed that hyperosmotic mannitol reduced the myocardial oxygen requirement of the ischemic heart. Mannitol dilated large collateral conductance vessels in addition to improving blood flow through the region of myocardial ischemia. Under conditions of ischemia induced by a prolonged reduction in coronary perfusion, hyperosmotic mannitol attenuated the progressive rise in vascular resistance. Direct morphologic examination of areas of myocardium subjected to total interruption of blood flow followed by reflow of blood revealed swelling of both myocardial and capillary endothelial cells early during the reflow period. The extent of swelling was substantially reduced with elevation of the extracellular osmolality with mannitol. Simarilty, osmolality elevation strikingly reduced the extent of eventual myocardial necrosis following prolonged periods of reflow of blood.
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PMID:Effects of hyperosmotic mannitol in reducing ischemic cell swelling and minimizing myocardial necrosis. 125 68

The metabolic and hemodynamic effects of methylprednisolone sodium succinate (40 mg/kg body weight) after acute myocardial ischemia were determined in 24 heparinized mongrel dogs. Myocardial ischemia was produced by ligation of the left anterior descending coronary artery. Catheters in the coronary sinus and the vein draining the left anterior descending coronary arterial area were used to collect blood samples from nonischemic and ischemic myocardium. Lactate, pyruvate, glucose, free fatty acids and oxygen were measured in arterial and venous blood from ischemic and nonischemic areas before and 3, 30 and 60 minutes after myocardial ischemia in animals with (Group II) and without (Group I) steroid treatment. In both Groups I and II glucose, lactate, free fatty acids, oxygen and coronary blood flow in nonischemic areas were not significantly changed, whereas glucose uptake in ischemic areas was significantly increased with myocardial ischemia and remained elevated. In Group I lactate uptake in ischemic areas became negative after coronary arterial ligation and remained so; in Group II, it increased after 30 (70%) and 60 (111%) minutes. Free fatty acid uptake in ischemic areas was reduced after myocardial ischemia in Group I, but in Group II it increased after 30 (224%) and 60 minutes (173%), and there was a concomitant increase in oxygen uptake. Pyruvate uptake in nonischemic areas decreased after 60 minutes in Group I, whereas it was reduced after 30 (68%) and 60 minutes (513%) in Group II. The changes were similar in ischemic myocardium. There were no significant changes in hemodynamic indexes. Coronary blood flow in ischemic areas decreased in Group I after myocardial ischemia and further after 30 and 60 minutes, but in Group II it increased after 30 (82%) and 60 minutes (53%). The data indicate that administration of methylprednisolone results in improved collateral blood flow into the infarcted area and a significantly improved metabolic response of ischemic myocardium. The glucocorticoid may also have a direct benefical effect on carbohydrate metabolism and cause the increased pyruvate neccesary to maintain the generation of energy-producing substrates. The results also suggest that methylprednisolone increases cell survival time and results in greater salvage of ischemic myocardium.
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PMID:Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia. 125 93

With a canine model of myocardial infarction [ligation of the left anterior descending (LAD) coronary artery] and an intracellular stain for lactic dehydrogenase (LDH) to directly measure size of infarction, the influence of 30 mg. per kilogram of methylprednisolone sodium succinate was evaluted. The intravenous administration of a pharmacologic dose of methylprednisolone one, 2, or 3 hours after the onset of myocardial infarction significantly reduced the ultimate extent of myocardial necrosis, with the greatest reduction seen following the injection of the drug one hour after ligation. The left atrial pressure was significantly decreased by corticosteroid administration, whereas the cardiac index and peripheral vascular tone were improved insignificantly. Inconsistent and/or insignificant effects were observed in the systemic and coronary sinus blood gases and in those indices of myocardial metabolism which were determined. The potential impact of these findings on the clinical applicability of methylprednisolone sodium succinate in acute myocardial ischemia is discussed.
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PMID:Temporal factors in the reduction of myocardial infarct volume by methylprednisolone. 127 68

Dofetilide is a potent and selective class III antiarrhythmic agent that is under development for the treatment of re-entrant tachyarrhythmias (ventricular tachycardia/ventricular fibrillation, atrial fibrillation/atrial flutter, and paraoxysmal supraventricular tachycardia). In animal studies, dofetilide selectively inhibits the rapid component of the time-dependent outward potassium current (IKr) and therefore increases the effective refractory period and action potential duration without affecting the fast inward sodium current. Studies in dogs have shown that dofetilide (a) prolongs the effective refractory period in a dose-dependent manner, (b) elevates ventricular fibrillation threshold, (c) facilitates conversion of electrically induced ventricular fibrillation or fibrilloflutter to sinus rhythm, (d) does not influence conduction within the His-Purkinje system or within the myocardium, (e) does not impair cardiac contractility, and (f) reduces dispersion of ventricular repolarization. Dofetilide has been administered to healthy volunteers as well as to patients with ischemic heart disease or with supraventricular arrhythmias; the compound has generally been well tolerated. Side effects have occasionally been reported, but have generally been transient and mild and occur in placebo-treated subjects as well. No clinically significant changes in laboratory safety tests have been detected. The pharmacokinetic profile of dofetilide both in healthy volunteers and patients includes a linear dose-plasma concentration relationship and also a linear plasma concentration-QTc relationship. The terminal plasma elimination half-life is approximately 9-10 h and systemic bioavailability in the region of 100%. The elimination pattern is balanced, with 50% being excreted unchanged via the kidney, the remaining 50% being metabolized in the liver to inactive metabolites, with greater than 90% of circulating drug-related material being unchanged dofetilide. After intravenous administration of the compound, a slight hysteresis in the plasma drug level-QTc relationship has been detected. Pharmacodynamic data demonstrate dose- and concentration-dependent effects on myocardial repolarization as evidenced by prolongations of the QTc interval. This is reflected in significant prolongations in the effective and functional refractory periods and monophasic action potential duration throughout the myocardium. No effects on sinus node function, conduction parameters, or cardiac contractility have been detected in any of the clinical studies, supporting the contention that dofetilide is a highly selective class III antiarrhythmic agent.
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PMID:Dofetilide, a novel class III antiarrhythmic agent. 127 16

Myocardial ischemia and reperfusion cause coronary vascular injury involving both the large epicardial arteries and the microcirculation. Although the mechanisms are unclear, leukocytes appear to play an important role. Since the methylxanthine derivative pentoxifylline (PTX) decreases neutrophil activity in vitro, we hypothesized that it might diminish coronary vascular injury due to ischemia and reperfusion. We investigated the effects of PTX on coronary microvascular and epicardial artery injury in open chest, anesthetized dogs undergoing moderate (60 min) or more prolonged (90 min) ischemia due to left anterior descending coronary artery occlusion followed by 60 min of reperfusion. As an index of microvascular injury, we assessed regional permeability with a dual radioisotope protein leak index (PLI) method. Both ischemic periods with reperfusion increased the PLI of severely ischemic (flow less than or equal to 20/ml/min/100 g) myocardium by 2.5- and 3-fold, respectively, compared to nonischemic (flow greater than or equal to 100 ml/min/100 g) myocardium. Treated dogs received PTX (20 mg/kg bolus plus 0.1 mg/kg/min infusion) before ischemia. PTX reduced the increase in the PLI by 40% after 60 min of ischemia (PLI = 5.87 +/- 0.48 vs. 4.10 +/- 0.52 untreated vs. PTX-treated; P less than .05), and by 25% after 90 min of ischemia (6.84 +/- 0.49 vs. 4.84 +/- 0.42; P less than .05). The amount of protein leak was inversely related to ischemic blood flow, and the magnitude of this relationship was significantly reduced in PTX-treated animals. In arterial rings from untreated dogs exposed to 90 min of ischemia followed by reperfusion, there was impaired relaxation to ADP and acetylcholine, but not to sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary vascular injury due to ischemia-reperfusion is reduced by pentoxifylline. 131 65

Reports have suggested that the fast inward sodium current (INa) in cardiac tissues may be modulated by beta-adrenergic stimulation and that such modulation may affect conduction in the setting of myocardial ischemia and infarction. However, many of these studies have used dissociated myocytes or broken cell preparations, whose responses need not necessarily reflect those of syncytial preparations. To investigate further the possibility that beta-adrenergic stimulation of INa may differ in various preparations, we compared the effects of the beta-agonist isoproterenol (ISO) on syncytial canine Purkinje fibers and ventricular muscle preparations, as well as isolated ventricular myocytes. Alterations of the maximum rate of rise of the action potential upstroke (Vmax) were used as an index of changes of INa. ISO (1 microM) had no effect on Vmax of upstrokes of normally polarized (fast responses) or partially depolarized (elevated [K+]o, depressed fast responses) syncytial ventricular muscle preparations or Purkinje fibers. In contrast, lower concentrations of ISO (0.5-1.0 microM) modulated Vmax of isolated ventricular myocytes, depending on the technique used to monitor transmembrane potential. When 2.7 M KCl-filled microelectrodes were used, ISO reduced Vmax of partially depolarized myocytes without affecting Vmax of normally polarized myocytes. However, when myocytes were dialyzed using patch pipettes, ISO reduced Vmax of partially depolarized myocytes and increased Vmax of normally polarized myocytes, effecting a hyperpolarized shift of the normalized inactivation curve relating Vmax to resting membrane potential. The different beta-adrenergic responses of syncytial preparations and nondialyzed and dialyzed myocytes suggest that differences in the ionic or metabolic condition of the preparations likely alter cAMP-dependent responses and channel phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenergic modulation of fast inward sodium current in canine myocardium. Syncytial preparations versus isolated myocytes. 131 13

A 56-year-old diabetic man underwent heart transplantation for end-stage ischemic heart disease; fever, progressive thrombocytopenia, and hepatitis developed 8 weeks after transplantation. Cytomegalovirus was cultured from the serum buffy coat. In spite of therapy with high-dose ganciclovir sodium, the patient died on the seventy-seventh postoperative day. Autopsy revealed a previously unsuspected high-grade B-cell lymphoma with extensive hepatic replacement.
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PMID:Lymphoma mimics cytomegalovirus-induced hepatitis in a heart transplant recipient. 132 29

Myocardial ischemia was shown to lead to modification of structural and functional organization of rat erythrocyte membranes. Thus, it was found that the activity of Na+, K+-ATP-ase markedly decreased, while accumulation of LPO products and of lysophosphatidylcholine (lyso--PC) took place in erythrocyte membranes of rats subjected to myocardial ischemia. Using nonpenetrating modifier trinitrobenzosulfonic acid, an increase in the content of modified phosphatidylethanolamine in erythrocyte membranes of ischemic rats was revealed as compared to the membranes of control animals. The intravenous administration of gangliosides (30 mg/kg) resulted in partial normalization of Na+, K+(-)ATPase activity, of LPO product and lysoPC content and of transbilayer distribution of lipids.
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PMID:[Ganglioside protection of the erythrocyte membranes in myocardial ischemia]. 133 4

Isolated perfused rat heart model was used to observe the protective effects of berbamine on myocardial ischemia/reperfusion injury. The hearts were significantly injured by 40 min global ischemia followed by 20 min reperfusion. Berbamine could significantly improve heart function, prevent ventricular fibrillation, reduce CK release, preserve Na,K-ATPase activity, and reduce Na+ gain and K+ loss during ischemia and Ca2+ overload during reperfusion. With the use of low temperature ESR technique, in hearts subjected to 40 min ischemia and 15 sec reperfusion, oxygen-centered free radical signals became much more intense. In the presence of berbamine, these signals decreased. Results showed that berbamine could alleviate myocardial ischemia/reperfusion injury. This effect might be due to: 1) preserved myocardial Na,K-ATPase activity and inhibition of sodium overload at the end of ischemia, which might further lead to attenuation of reperfusion-induced calcium overload, and 2) reduction of oxygen free radical generation during reperfusion.
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PMID:Mechanisms of protective effects of berbamine on ischemia/reperfusion injury in isolated rat heart. 133 20


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