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

Ischemia of the heart is accompanied by the tissue accumulation of long-chain fatty acids and their metabolic derivatives such as beta-hydroxy fatty acids and fatty acyl-CoA and acyl-L-carnitine esters. These substances might be detrimental for proper myocardial function. Previously, it has been suggested that intracellular lipid binding proteins like cytoplasmic fatty acid-binding protein (FABP) and acyl-CoA binding protein (ACBP) may bind these accumulating fatty acyl moieties to prevent their elevated levels from potentially harmful actions. In addition, the suggestion has been made that the abundantly present FABP may scavenge free radicals which are generated during reperfusion of the ischemic heart. However, these protective actions are challenged by the continuous physico-chemical partition of fatty acyl moieties between FABP and membrane structures and by the rapid release of FABP from ischemic and reperfused cardiac muscle. Careful evaluation of the available literature data reveals that at present no definite conclusion can be drawn about the potential protective effect of FABP on the ischemic and reperfused heart.
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PMID:Significance of cytoplasmic fatty acid-binding protein for the ischemic heart. 823 60

The effects of global ischemia on the contractile system and on sarcoplasmic reticulum (SR) function were studied by measuring the isometric tension and the SR Ca2+ release activity of chemically skinned cardiac fiber preparations from seven patients undergoing open-heart surgery. Ten minutes of ischemia caused 1) a decrease in the myofilament sensitivity to Ca2+ (expected Ca2+ concentration giving half-maximal tension; from 0.69 +/- 0.04 to 1.38 +/- 0.06 microM, n = 7) and in the cooperativity index (Hill coefficient; from 2.61 +/- 0.45 to 0.92 +/- 0.15, n = 7), 2) a decrease in myosin light chain phosphorylation, and 3) a 300% increase in the threshold caffeine concentration for SR Ca2+ efflux channel activation, with a 30% reduction in the rate of Ca2+ release by caffeine at threshold concentrations and a 23% reduction in the rate of release by 20 mM caffeine. After preincubation with 5 microM trifluoperazine, a calmodulin antagonist, the caffeine threshold of ischemic and control cardiac muscle became comparable. Most changes were reversed by reperfusion, while the caffeine threshold was still two times greater than control. These results indicate that ischemia caused alterations of the cardiac muscle contractile apparatus and the SR that were reversed only after reperfusion.
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PMID:Effects of ischemia on sarcoplasmic reticulum and contractile myofilament activity in human myocardium. 823 22

Cromakalim is a member of the new antihypertensive drug family possessing an action that involves an increased K efflux in vascular and cardiac muscle. We studied the contribution of opening of ATP-sensitive K channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na, K, Ca and Mg in isolated rat hearts. After 30 min of global ischemia, cromakalim (1 to 30 microM) failed to reduce reperfusion arrhythmias. On the postischemic-reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (duration of ischemia was reduced to 25 min), cromakalim treatment was associated with a higher incidence of reperfusion ventricular fibrillation (VF) and ventricular tachycardia (VT) as compared to the controls (100% VF and 100% VT in treated vs. 41% VF and 50% VT in controls, P < .05). Proarrhythmic effects of cromakalim were also reflected in a maldistribution of myocardial ions. At concentrations of 3, 10 and 30 microM of glibenclamide, a K channel blocker, a significant reduction in the incidence of reperfusion-induced VF and VT was observed, and an attenuation in the maldistribution of myocardial ion contents induced by ischemia/reperfusion was found. The reduction in myocardial contractility was detected at relatively high concentrations (10 and 30 microM) in both cromakalim- and glibenclamide-treated groups. The proarrhythmic effect of cromakalim (30 microM) was abolished by 3 microM of glibenclamide, suggesting that the increased tendency to develop reperfusion arrhythmias is associated with the cromakalim-induced K efflux.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potassium channel openers and blockers: do they possess proarrhythmic or antiarrhythmic activity in ischemic and reperfused rat hearts? 826 98

The present study was designed to test if prophylactic intravenous nifedipine or nitroglycerine could reduce myocardial damage after cardiopulmonary bypass. 45 patients scheduled for elective coronary artery bypass grafting were divided at random into three groups: Group 1: control; group 2: nifedipine (0.25 microgram/kg/min); group 3: nitroglycerine (1.5 micrograms/kg/min). Infusion period reached from the beginning of anaesthesia until crossclamp of the aorta. Myocardial damage was estimated by troponin T (TnT), CK-MB and ST-segment analysis of the ECG. TnT is a cardiospecific protein from the contractile apparatus of striated muscle cells. TnT-levels might provide a very sensitive marker of small amounts of cardiac muscle necrosis. It was tested with an ELISA/one-step sandwich-assay with streptavidin-technology [9]. Criteria for ischemia in the ST-segment analysis were (according to Smith et al. [19]): ST-depression > 1 mm from baseline or ST-elevation > 2 mm from baseline at J-point + 60 ms. Statistical interpretation was done by one- and two-factorial analyses of variance (including multivariate analyses of variance). Correlation between two variables was tested by regression analysis. A level of p < 0.05 was taken for indicating statistical significance. Biometrical data, circulation data and data from cardiopulmonary bypass were without significant differences among all groups (Tables 1 and 2). Starting from normal values (< 0.05 ng/ml) TnT significantly rose in all groups immediately after cardiopulmonary bypass and remained elevated until the forth day after operation (values between 0.4 and 0.6 microgram/ml) (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cardiac protection in heart surgery interventions by preventive drug administration before extracorporeal circulation. Studies with troponin T as a parameter for perioperative myocardial damage]. 830 54

Ca(2+)-release channel or ryanodine receptor is known to be involved in physiologic Ca(2+)-release from sarcoplasmic reticulum in skeletal and cardiac muscle. A variety of chemical oxidants and in particular SH-oxidizing reagents have been shown to activate Ca2+ release. However, the role of the oxidative modification of the channel in the physiologic mechanism(s) of Ca2+ release and in pathologic states of the muscle remains to be elucidated. Ascorbate/iron redox couple is known to be an efficient generator of oxygen radicals and semidehydroascorbyl radicals. Ascorbate/iron was shown to be released from cardiomyocytes during ischemia-reperfusion and was suggested to be involved in the ischemia-reperfusion injury and cardiomyocyte death. To understand the potential contribution of ascorbate/iron to Ca2+ release mechanism(s), calcium release channels from skeletal sarcoplasmic reticulum (SR) were reconstituted in artificial planar bilayers to examine the effects of this redox couple on the channel activity. Ascorbate elicited a transient (about 2 min) but dramatic increase of open-time probability of the channel. At pCa = 7.0, the presence of EGTA blocked ascorbate induced activation of release channels. However, when exogenous iron was added, ascorbate activated Ca2+ release channels, even in the presence of EGTA. ESR measurements demonstrated that semidehydroascorbyl radicals were generated from ascorbate in the absence of EGTA. The semidehydroascorbyl radical ESR signal was quenched by EGTA in the absence (but not in the presence) of exogenous iron. Thus, the production of ascorbyl radicals was associated with increased channel activity. In the presence of heparin, ascorbate plus iron elicited a long-lasting activation of the channel which had conductance gCa2+ = 100 pS characteristic for the ryanodine receptor and which could be blocked by the ryanodine channel inhibitor, ruthenium red. In conclusion the physiologically relevant redox couple--ascorbate/iron--at physiologic concentrations can activate Ca2+ channels in sarcoplasmic reticulum vesicles.
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PMID:Ascorbate/iron activates Ca(2+)-release channels of skeletal sarcoplasmic reticulum vesicles reconstituted in lipid bilayers. 831 55

The effect of direct electric current (DEC), 0.4 mA, on the ultrastructure of normal perfusing isolated heart and in the course of its postischemic reperfusion was studied on the model of isolated rat heart using Langedorf method. DEC was shown to exert a normalizing, membrane-stabilizing effect on the subcellular organization of isolated heart CMC in the course of its normothermic perfusion. The observed changes are considered to attest to the adaptive aspect of the current effect on the ultrastructure of the myocardium under these conditions. In ischemia-reperfusion, DEC also facilitated marked stabilization of cardiomyocytes membranes and stimulation of intracellular reparative processes of the affected cardiac muscle.
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PMID:[The characteristics of the action of a direct electric (galvanic) current on the ultrastructure of the normal perfused isolated heart and during its postischemic reperfusion]. 840 Jan 68

Depressed contractile function plays a primary role in the pathophysiology of acute myocardial ischemia. Intracellular acidification is an important factor underlying the inhibition of force production in the ischemic myocardium. The effect of acidosis to depress contractility is markedly greater in cardiac as compared to skeletal muscle; however, the molecular basis of this difference in sensitivity to acidosis is not clearly understood. In this report, we describe transgenic mice that express the fast skeletal isoform of troponin C (sTnC) in cardiac muscle. In permeabilized single cardiac myocytes the shift in the midpoint of the tension-pCa relationship (i.e., pCa50, where pCa is -log[Ca2+]) due to lowering pH from 7.00 to 6.20 was 1.27 +/- 0.03 (n = 7) pCa units in control cardiac TnC (cTnC) expressing myocytes and 0.96 +/- 0.04 (n = 11) pCa unit in transgenic cardiac myocytes (P < 0.001). The effect of pH to alter maximum Ca(2+)-activated tension was unchanged by TnC isoforms in these cardiac myocytes. In a reciprocal experiment, contractile sensitivity to acidosis was increased in fast skeletal muscle fibers following extraction of endogenous sTnC and reconstitution with purified cTnC in vitro. Our findings demonstrate that TnC plays an important role in determining the profound sensitivity of cardiac muscle to acidosis and identify cTnC as a target for therapeutic interventions designed to modify ischemia-induced myocardial contractile dysfunction.
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PMID:Skeletal troponin C reduces contractile sensitivity to acidosis in cardiac myocytes from transgenic mice. 841 50

The addition of a paramagnetic contrast agent reduces the magnetization transfer effect between the free and restricted proton pools in both agar phantoms and cardiac muscle tissue. This reduction is due to the reduction in the intrinsic T1 of the free proton pool and increases the signal observed after a given magnetization transfer sequence. Images of ex vivo piglet hearts were obtained with a segmented snapshot FLASH (fast low-angle shot) sequence with a 128 x 128 matrix, four segments, and two signals averaged, resulting in an imaging time of 7 seconds. Magnetization transfer was induced by applying a DANTE (delays alternating with nutations for tailored excitations) pulse sequence in the intersegment interval. This was an efficient method of inducing magnetization transfer because it excites the restricted proton pool across the full frequency spectrum. Ischemia due to occlusion of the left anterior descending branch of the coronary artery could be visualized after infusion of gadolinium diethylenetriaminepentaacetic acid-bis(methylamide) (DTPA-BMA). Although the ischemia could be seen with the basic sequence, the contrast between ischemic and non-ischemic tissue improved when the magnetization transfer sequence was included. The most marked improvements in magnetization transfer were achieved with low doses of Gd-DTPA-BMA.
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PMID:Effect of Gd-DTPA-BMA on magnetization transfer: application to rapid imaging of cardiac ischemia. 842 99

In the present study we compared the quantitatively most important, Pi-activated mechanisms for conserving ATP during ischemia in dog and rat cardiac muscle. Earlier studies by ourselves showed that dog heart, like all slow heart rate mammalian hearts examined, possesses the ability to inhibit its mitochondrial ATPase by binding IF1, the ATPase inhibitor protein, during ischemia. Rat heart, like other fast heart rate mammalian hearts studied, does not. The present study demonstrated that this IF1-mediated ATPase inhibition in ischemic dog heart, as in other slow heart rate hearts, appears to depend on matrix space acidification mediated largely by Pi-H+ symport via the mitochondrial Pi carrier. The present study further confirmed that maximal glycolytic flux rates are five- to sixfold greater in ischemic rat than in ischemic dog heart. Both of these systems are activated by increasing Pi concentration ([Pi]) during ischemia, and both appear to be regulated somewhat differently in dog than in rat heart. Thus intact dog heart mitochondria exhibited a [Pi]-dependent ATPase inhibition at low external pH, whereas rat heart mitochondria did not. The [Pi] required for maximal ATPase inhibition in dog heart mitochondria was approximately 6 mM. Although both dog and rat heart phosphofructokinase were stimulated by Pi, the enzyme in dog heart was maximally activated by approximately 6 mM Pi, whereas the rat heart enzyme required only approximately 3 mM Pi for its maximal stimulation under otherwise identical conditions. The most active nonmitochondrial ATPase in ischemic dog and rat cardiac muscle, the Ca(2+)-activated actomyosin ATPase, accounted for approximately one-half of the total nonmitochondrial ATPase activity in each species.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of ATP conservation during ischemia in slow and fast heart rate hearts. 843 Jul 69

Earlier studies by Rouslin and coworkers showed that, during myocardial ischemia in slow heart-rate species which include rabbits and all larger mammals examined including humans, there is an IF1-mediated inhibition of the mitochondrial ATPase due to an increase in the amount of IF1 bound to the ATPase (Rouslin, W., and Pullman, M.E., J. Mol. Cell. Cardiol. 19,661-668, 1987). Earlier work by Guerrieri and colleagues demonstrated that IF1 binding to bovine heart ESMP was accompanied by parallel decreases in ATPase activity and in passive proton conduction (Guerrieri, F., et al., FEBS Lett. 213, 67-72, 1987). In the present study rabbit was used as the slow heart-rate species and rat as the fast heart-rate species. Rat is a fast heart-rate species that contains too little IF1 to down regulate the ATPase activity present. Mitochondria were prepared from control and ischemic hearts and ESMP were made from aliquots by sonication at pH 8.0 with 2 mM EDTA. Oligomycin-sensitive ATPase activity and IF1 content were measured in SMP prepared from the control and ischemic mitochondrial samples. After identical incubation procedures, oligomycin-sensitive ATPase activity, oligomycin-sensitive proton conductivity, and IF1 content were also measured in ESMP samples. The study was undertaken to corroborate further what appear to be fundamental differences in ATPase regulation between slow and fast heart-rate mammalian hearts evident during total myocardial ischemia. Thus, passive proton conductivity was used as an independent measure of these regulatory differences. The results show that, consistent with the low IF1 content of rat heart cardiac muscle mitochondria, control rat heart ESMP exhibit approximately twice as much passive proton conductivity as control rabbit heart ESMP regardless of the pH of the incubation and assay. Moreover, while total ischemia caused an increase in IF1 binding and a commensurate decrease in passive proton conductivity in rabbit heart ESMP regardless of pH, neither IF1 content nor proton conductivity changed significantly in rat heart ESMP as a result of ischemia.
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PMID:ATPase activity, IF1 content, and proton conductivity of ESMP from control and ischemic slow and fast heart-rate hearts. 859 81


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