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)

Alternations of regional left ventricular myocardial function immediately after coronary artery branch ligation as related to the total left ventricular function were determined by utilizing left ventricular pressure-wall thickness loop in 6 anesthetized open-chest dogs. End-diastolic wall thickness was decreased immediately from 11.54+/-0.50 mm (standard error of the mean) of control to 10.99+/-0.50 mm in 5 to 10 min after ligation (p<0.05), while regional myocardial work calculated as the loop area, was also decreased from 27.5+/-6.1 to 19.3+/-5.8X10(3) dyn/cm (p<0.05), indicating that the local Frank-Starling curve at the myocardium was depressed during ischemia. At the site where the ligation did not have effect, end-diastolic wall thickness and the regional work did not change significantly. Analysis of the shape of the loop revealed that the myocardial shortening was incomplete during the systolic ejection phase, and that the myocardial relaxation occurred very early in the ventricular relaxation phase after ischemia without alterations in the isovolumic contraction phase. These findings are compatible with those reported on isolated cardiac muscle strips during anoxia. The left ventricular pressure-wall thickness loop is superior to the pressure-length loop in that the former can be applied easily for clinical purposes and that the former utilizes a more direct relationship of pressure to its generator than the latter. Thus, primary alterations of myocardial function during ischemia were clarified accurately by utilizing the present method in the left ventricle in situ.
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PMID:Alterations of myocardial function during early stages of mild experimental ischemia in dogs determined by left ventricular pressure-wall thickness loop. 742 Jul 35

Previous studies show that (1) hypoxemia depletes immature myocardium of amino acid substrates and their replenishment improves ischemic tolerance, (2) reoxygenation on cardiopulmonary bypass causes oxygen-mediated damage without added ischemia, and (3) this damage may be related to the nitric oxide-L-arginine pathway that is affected by amino acid metabolism. This study tests the hypothesis that priming the cardiopulmonary bypass circuit with glutamate and aspartate limits reoxygenation damage. Of 22 immature Duroc-Yorkshire piglets (< 3 weeks old), five were observed over a 5-hour period (control), and five others underwent 30 minutes of CPB without hypoxemia (cardiopulmonary bypass control). Twelve others became hypoxemic by reducing ventilator inspired oxygen fraction to 6% to 7% (oxygen tension about 25 mm Hg) before reoxygenation on cardiopulmonary bypass for 30 minutes. Of these five were untreated (no treatment), and the cardiopulmonary bypass circuit was primed with 5 mmol/L glutamate and aspartate in seven others (treatment). Left ventricular function before and after bypass was measured by inscribing pressure-volume loops (end-systolic elastance). Myocardial conjugated diene levels were measured to detect lipid peroxidation, and antioxidant reserve capacity was tested by incubating cardiac muscle with the oxidant t-butylhydroperoxide to determine the susceptibility to subsequent oxidant injury. CPB (no hypoxemia) allowed complete functional recovery without changing conjugated dienes and antioxidant reserve capacity, whereas reoxygenation injury developed in untreated hearts. This was characterized by reduced contractility (elastance end-systolic recovered only 37% +/- 8%*), increased conjugated diene levels (1.3 +/- 0.1 vs 0.7 +/- 0.1*), and decreased antioxidant reserve capacity (910 +/- 59 vs 471 +/- 30 malondialdehyde nmol/g protein at 2 mmol/L t-butylhydroperoxide*). In contrast, priming the cardiopulmonary bypass circuit with glutamate and aspartate resulted in significantly better left ventricular functional recovery (75% +/- 8% vs 37% +/- 8%*), minimal conjugated diene production (0.8 +/- 0.1 vs 1.3 +/- 0.1*), and improved antioxidant reserve capacity (726 +/- 27 vs 910 +/- 59 malondialdehyde nmol/g protein*) (*p < 0.05 vs cardiopulmonary bypass control). We conclude that reoxygenation of immature hypoxemic piglets by the initiation of cardiopulmonary bypass causes myocardial dysfunction, lipid peroxidation, and reduced tolerance to oxidant stress, which may increase vulnerability to subsequent ischemia (i.e., aortic crossclamping). These data suggest that supplementing the prime of cardiopulmonary bypass circuit with glutamate and aspartate may reduce these deleterious consequences of reoxygenation.
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PMID:Studies of hypoxemic/reoxygenation injury: without aortic clamping. VIII. Counteraction of oxidant damage by exogenous glutamate and aspartate. 747 74

Reducing reperfusion injury is effective in reducing flap loss after prolonged ischemia. Anti-inflammatory therapy reduces reperfusion injury in canine cardiac muscle and ex vivo rat cremaster muscle; however, to date, there are no studies involving the use of anti-inflammatory agents in ischemic skin flaps. This study was designed to assess the effects of dexamethasone and indomethacin on the viability of rat island groin flaps subjected to 10 hours of ischemia. The ischemic control and the treatment group flaps were subjected to 10 hours of ischemia by clamping the inferior epigastric vascular pedicle. The treatment groups received either intravenous dexamethasone or intravenous indomethacin after the flap vascular pedicles were clamped. Our results showed significant improvement (p < 0.05, Fisher's exact test) in ischemic flap survival using dexamethasone. The specific mode of action of dexamethasone was not investigated; however, its anti-inflammatory effects were most likely responsible for the improvement of flap survival by suppressing the circulating neutrophil and decreasing reperfusion injury. Dexamethasone is easily available for clinical use, and its use should be considered in cases of prolonged ischemia in skin flaps.
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PMID:Reducing ischemia-reperfusion injury in rat island groin flaps using dexamethasone. 750 23

A major determinant of survival in patients with advanced viral or bacterial infection, or following severe trauma or burns complicated by multiple organ failure, is the combination of clinical signs termed the systemic inflammatory response syndrome (SIRS). SIRS is characterized by hypotension, tachypnea, hypo- or hyperthermia and leukocytosis as well as other clinical signs and symptoms, including a depression in myocardial contractile function. Heart failure complicating systemic sepsis or other causes of SIRS is usually not accompanied by coronary artery ischemia due to hypotension, myocardial necrosis, or marked cardiac interstitial inflammatory infiltrates, and thus the cause of cardiac contractile dysfunction in this syndrome has remained unclear. However, recent evidence has implicated an endogenous nitric oxide (NO) signalling pathway within cardiac myocytes and other cellular constituents of cardiac muscle, including the microvascular endothelium, as a possible contributor to the pathogenesis of heart failure in this syndrome. Cardiac myocytes are now known to express both constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) activities. Activation of cNOS appears to modulate cardiac myocyte responsiveness to muscarinic cholinergic and beta-adrenergic receptor stimulation. Induction of iNOS by soluble inflammatory mediators, including cytokines, causes a marked depression in myocyte contractile responsiveness to beta-adrenergic agonists. Thus, inappropriate activation of cNOS or excessive or prolonged induction of iNOS in the myocardium may contribute to cardiac dysfunction complicating SIRS.
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PMID:Myocardial contractile dysfunction in the systemic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes. 753 82

We hypothesized that the slowly inactivating component of Na+ current, which is an integral part of the Na+ window current, is a major pathway for Na+ loading during myocardial ischemia. The putative protective effects of tetrodotoxin (TTX) and R-56865, at concentrations that selectively blocked the Na+ window current, as assessed by action potential plateau shortening without affecting maximum upstroke velocity (Vmax), were examined in isolated Langendorff-perfused guinea pig hearts subjected to 50 min of normothermic global ischemia and 60 min of reperfusion. In papillary muscles, TTX reduced action potential duration at > or = 10 nM but reduced Vmax only at > or = 1 microM. R-56865 (10 nM-10 microM) failed to affect Vmax but concentration dependently reduced action potential duration. Ischemia-induced cardiac dysfunction, including increases in left ventricular end-diastolic pressure and lactate dehydrogenase and creatine phosphokinase release at reperfusion, was attenuated by TTX and R-56865 (0.1-320 nM). Ischemic contracture (increase in left ventricular end-diastolic pressure) was abolished by drug concentrations as low as 1 nM, whereas higher concentrations (> 10 nM) of TTX and R-56865 were required to restore systolic function at reperfusion. TTX and R-56865 had little or no effect on hemodynamic variables. Evidence is provided of pronounced and direct cardioprotective effects of low concentrations of R-56865 and TTX in cardiac muscle during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alleviation of contractile dysfunction in ischemic hearts by slowly inactivating Na+ current blockers. 765 17

The effects of acute ischemia on conduction velocities in the longitudinal (theta L) and transverse (theta T) fiber axis were determined from epicardial activation patterns, recorded with 48 bipolar electrodes (plaque electrode, 25 x 35 mm) on the left anterior ventricular wall of eight dogs and the posterior wall of seven dogs. During left ventricular stimulation (cycle length = 300 msec) in the center of the plaque electrode, theta L, theta T, and the ratio of longitudinal to transverse conduction velocities (theta L/T) were measured before and 2 to 5 minutes after occlusion of the left anterior descending coronary artery or the left circumflex coronary artery. During the control state theta L was greater than theta T demonstrating anisotropic properties of cardiac muscle, not only in the anterior but also in the posterior wall. During acute ischemia theta L and theta T were decreased from the control value and theta T was decreased by a greater extent than theta L resulting in an increase in theta L/T from 1.83 +/- 0.31 (mean +/- SD) to 2.19 +/- 0.36 in the anterior wall and from 1.58 +/- 0.17 to 1.92 +/- 0.28 in the posterior wall. During ventricular fibrillation some lines of conduction block were parallel to the long axis of epicardial muscle fiber bundle and the others were perpendicular. In conclusion, acute ischemia increased anisotropic conduction (theta L/T) in the epicardial ventricular muscle mainly due to greater reduction in theta T, in the anterior and the posterior wall. This augmented anisotropic ventricular conduction may have some relation to the initiation of ventricular fibrillation during acute ischemia.
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PMID:Effects of acute ischemia on anisotropic conduction in canine ventricular muscle. 769 Sep 34

Muscle necrosis has been frequently observed in cardiomyoplasty patients and in experimental animal studies. The purpose of this study was to determine if heat shock could provide protection to skeletal muscle as has been shown in cardiac muscle. A 15-minute heat shock at 42 degrees C resulted in an immediate increase in HSP72 mRNA and was followed within 3 hours by a two-fold increase in HSP72. Surgical dissection of the latissimus dorsi muscle (LDM) followed by an ischemic period resulted in a two-fold increase in HSP72 in control LDM, whereas the already high levels in the heat-shocked LDM increased only slightly with surgery and ischemia. Citrate synthase activity and tissue histology indicated that heat shock did not protect the LDM from the imposed surgical trauma and ischemia insults used in this study.
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PMID:Cardiomyoplasty: preservation of the latissimus dorsi muscle. 777 73

The role of reactive metabolites of oxygen, oxygen radicals (O-Rs), as mediators of potentially arrhythmogenic alterations in cellular electrical properties and contractile dysfunction of cardiac muscle during reperfusion after ischemia was investigated. Electrical and mechanical activities of arterially perfused guinea pig right ventricular walls were recorded simultaneously with intracellular microelectrodes and a force transducer. Preparations were maintained in Krebs-Henseleit solution (perfusion rate, 1.5 mL/min) and subjected to 30 minutes of no-flow ischemia followed by 60 minutes of reperfusion or pretreated with O-R scavengers (superoxide dismutase, 50 U/mL; catalase, 600 U/mL; and mannitol, 2 mmol/L) for 10 to 20 minutes, followed by 30 minutes of ischemia and 60 minutes of reperfusion. Reperfusion in untreated preparations caused (1) depolarization of resting membrane potential by 8 to 10 mV and slow recovery of action potential duration requiring 60 minutes to attain the preischemic duration, (2) tachyarrhythmias and premature action potentials, (3) postischemic contractile dysfunction, and (4) increased coronary perfusion pressure in untreated preparations. Pretreatment with scavenger cocktail affected neither electrical nor contractile activity before or during no-flow ischemia, but it (1) accelerated recovery of resting membrane potential and action potential duration, (2) reduced the incidence of tachyarrhythmia, (3) improved contractile function, and (4) inhibited the rise in perfusion pressure on reflow. Reperfusion with an exogenous O-R-generating system containing xanthine/xanthine oxidase (X/XO, 2 mmol/L:10 mU/mL) inhibited recovery of action potential duration and contractility. Treatment of normoxic arterially perfused right ventricular walls with X/XO caused a decline in action potential duration by approximately 20% within 30 minutes. In contrast, X/XO caused a 30% increase in the duration of action potentials in superfused papillary muscles or small strips of right ventricular walls over the same time period. Pretreatment with sodium nitroprusside (10 mumol/L) inhibited the decline in duration induced by X/XO in normoxic right ventricular walls but was without effect on prolongation due to X/XO in papillary muscles. Reperfusion with nitroprusside after no-flow ischemia caused (1) accelerated recovery of preischemic action potential configuration, (2) a significant decline in the incidence of reperfusion arrhythmias, (3) improved postischemic contractile performance, and (4) inhibition of the increase in perfusion pressure associated with reflow. The data indicate that slow recovery of the action potential duration caused by O-Rs in reperfusion cannot be explained by the direct effects of O-Rs on cardiac myocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Arrhythmia and delayed recovery of cardiac action potential during reperfusion after ischemia. Role of oxygen radical-induced no-reflow phenomenon. 778 73

ATP-sensitive potassium (K+ATP) channel openers such as cromakalim and pinacidil exhibit both potent vasodilatory and anti-ischemic properties. U-89232, a cyanoguanidine analog of cromakalim, has recently been found to exhibit myocardial protection during ischemia without altering in vivo hemodynamics. We examined the effects of U-89232, cromakalim and pinacidil in isolated vascular and cardiac tissue and tested whether glyburide, a KATP channel blocker, could antagonize their effects. All three compounds produced concentration-dependent relaxation in isolated vascular segments, with cromakalim being approximately 100-fold more potent than either pinacidil or U-89232. Glyburide completely antagonized the effects of pinacidil but merely blunted the effects of cromakalim and U-89232. In an isolated rabbit cardiac tissue preparation, U-89232 had little effect on maximum tension in cardiac muscle, whereas cromakalim and pinacidil significantly decreased maximum developed tension in a concentration-dependent manner. Glyburide effectively antagonized the effects of cromakalim and pinacidil in cardiac tissue. These data suggest that U-89232, although chemically related to cromakalim, possesses activity which is not common to known potassium channel openers.
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PMID:Comparative effects of the potassium channel openers cromakalim and pinacidil and the cromakalim analog U-89232 on isolated vascular and cardiac tissue. 797 25

The prognosis of patients with coronary artery disease (CAD) is mainly influenced by organic factors such as cardiac muscle loss and extent of CAD. The aim of this study was to investigate whether a functional factor--reversible myocardial ischemia at rest--plays an independent prognostic role. Thus, 2 groups of patients were studied and followed up for 46 +/- 32 months: 1 group (483 patients) had ischemic electrocardiographic changes only on effort and another group (224 patients) both on effort and at rest. The 2 groups did not differ significantly as to age, gender, coronary risk factors, baseline electrocardiographic abnormalities, incidence of previous myocardial infarction, angiographic left ventricular dysfunction, and extent of coronary stenoses (> or = 50% diameter reduction). There were 65 deaths (40 of which were from cardiac causes) during the 5-year follow-up. Despite the similar incidence of known predictors of prognosis, Kaplan-Meier survival analysis revealed a significantly lower 5-year survival rate in patients with mixed (84.4%) rather than exertional (92.1%) ischemia (p < 0.05 by Mantel-Haenszel test). If only cardiac causes of deaths were considered, the 5-year survival rate was still lower in patients with mixed (89.6%) rather than exertional (93.9%) ischemia. Finally, reversible ischemia at rest was an independent predictor of survival by Cox multivariate regression analysis, preceded only by the extent of CAD and left ventricular dysfunction. Thus, reversible ischemia at rest plays an independent negative role in the long-term clinical outcome of patients with CAD and positive exercise stress test results.
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PMID:Clinical features and prognostic implications of myocardial ischemia at rest in patients with exertional angina pectoris. 805 23


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