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

The activity of the adrenergic system plays an important role in the genesis of malignant arrhythmias and the spreading of the infarcted zone in acute myocardial ischemia. Acute myocardial ischemia induces an increased activity of adenylyl cyclase. This sensitization at the enzyme level as shown in the isolated perfused rat heart occurs rapidly after the onset of ischemia (5-15 minutes) and is rapidly reversible on reperfusion. With prolonged ischemia, it is only transient and is followed by a gradual loss of the adenylyl cyclase activity. The increased activity of adenylyl cyclase is even retained after partial purification, suggesting a covalent modification of the enzyme. Blockade of alpha 1-adrenergic receptors does not prevent this sensitization, demonstrating that it occurs independently of alpha 1-adrenergic receptor activation. Only blockade of protein kinase C by various inhibitors, such as polymyxin B or staurosporine, is able to completely prevent this sensitization process. Moreover, in acute myocardial ischemia an activation of protein kinase C could be identified using its translocation from the cytosol to the particulate fraction as an indicator. Blockade of alpha 1-adrenergic receptors using prazosin fails to prevent the activation of protein kinase C and consequently the sensitization of the adenylyl cyclase system, indicating that the ischemia-induced translocation of protein kinase C occurs independently of alpha 1-adrenergic receptors. These data characterize for the first time an important interaction of two effector enzymes of two distinct signal transduction pathways, i.e., the adenylyl cyclase system and the protein kinase C system in acute myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha 1-receptor-independent activation of protein kinase C in acute myocardial ischemia. Mechanisms for sensitization of the adenylyl cyclase system. 131 40

Reperfusion injury in early myocardial ischemia was studied in the dog with special reference to sarcoplasmic reticulum (SR) and contraction bands. Acute myocardial ischemia (I) was induced by occlusion of the left anterior descending coronary artery (LAD) for 10, 20 and 30 min followed by reperfusion for 15 min (R). Ca(++)-ATPase activity of SR in 10-min-R-Group was significantly reduced to 60% of control activity, but activity of 10-min-I-Group remained near the control level in subendomyocardium (Endo). ATPase activity in 30-min-I-Group diminished to 60% of control activity in Endo and it was similar for 30-min-R-Group. In ischemic myocardium, composition of major ATPase protein decreased significantly in 30-min-I-Group and similar reduction was observed in 20-min-R-Group in Endo. In morphology proportion of appearance of contraction bands in Endo was significantly increased in 20-min or longer-R-Groups. These results suggest that reperfusion injury is likely to occur when coronary artery is reflowed after 10 min of ischemia. This may be caused by increased intracellular Ca++ at a very early stage of reperfusion period, and reperfusion injury may be induced due to acceleration in the necrotic process of the membrane system in the myocytes during ischemia.
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PMID:Study on reperfusion injury on sarcoplasmic reticulum in acute myocardial ischemia. 153 89

Acute myocardial ischemia is the primary cause of concern during myocardial infarction and unstable angina, and the cornerstone of modern therapy is rapid establishment of antegrade blood flow. The ultimate success of reperfusion depends on the duration and severity of ischemia before revascularization. Even brief ischemia occurring during angioplasty may cause reversible myocardial dysfunction. Several interventions are available to minimize the negative effects of acute myocardial ischemia. Synchronized coronary venous retroperfusion is a myocardial support technique in which autologous arterial blood is shunted from the femoral artery into the ischemic myocardium via the coronary sinus. Retroperfusion has been studied clinically during angioplasty and has been shown to ameliorate and delay the onset of ischemia. It has also been beneficial during abrupt closure of the coronary artery after angioplasty as a bridge to definitive therapy. Preliminary reports have indicated the efficacy of retroperfusion in medically refractory unstable angina. Because of its retrograde approach, this technique may serve as an alternate route to an otherwise inaccessible, ischemic myocardium for delivery of blood and other cardioprotective agents.
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PMID:Coronary veins: an alternate route to ischemic myocardium. 154 8

Acute myocardial ischemia and reperfusion in rats increased glutamic oxalacetic transaminase (GOT), non-esterified fatty acid (FFA), malondialdehyde (MDA) content. Furyl-dihydropyridines I 10 mg.kg-1 decreased the release of GOT, FFA, MDA of ischemic myocardium, and prevent ischemia-reperfusion arrhythmia. Furyl-dihydropyridines I increased Na, K-ATPase activity and N-acethylneuraminic acid (NANA) content of erythrocyte membranes, inhibited Ca-ATPase activity of erythrocyte membranes in rats. The results suggested that the mechanism of protecting the ischemic-reperfused myocardium might be associated with the inhibition of cellular lipid peroxidation and Ca-ATPase activity of cell membranes.
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PMID:[Effects of furyl-dihydropyridines I on lipid peroxides of ischemic myocardium and ATPases activity of erythrocyte membranes in rats]. 166 69

Experimental studies were conducted into 170 adult male Wistar rats for the purpose of analysis of cellular adaptation processes of the myocardium to acute ischemia. One group of the animals were exposed to physical endurance training, i.e. 180 h of swimming exercises, up to 3 h daily. Positive verification of cardiac hypertrophy was considered a measure of accomplished cellular adaptation. Training-induced increase of relative and absolute heart weight was 25 and 30%, respectively. Acute myocardial ischemia had been produced by ligature of the left coronary artery. There were no significant differences between trained and untrained animals for incidence and size of infarction and postoperative lethality, while cardiac decompensation was less often recorded from trained animals. To study cellular adaptation as well as differences between trained and untrained animals, tissue samples were taken from the non-ischemic part of the left ventricle and checked by means of histology, electron microscopy, morphometry, quantitative histochemistry, and histo-autoradiography 1, 2, 4, 7, and 14 days after occlusion of the coronary artery. The studies have shown endurance training to result in unambiguous modification of structural as well as functional response of the nonischemic heart. Included in such structural modification at cellular level are significant changes in mitochondrial membranes, sarcoplasmic reticulum, and T-system. Structural modification was reflected in changes to the oxidative enzymes and DNA metabolism. Different patterns of cellular reaction could be positively verified up to 14 days after myocardial infarction.
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PMID:Morphometric, histochemical and autoradiographic studies on myocardial cells in experimental cardiac hypertrophy and ischemia. 182 34

Acute myocardial ischemia results from an increased cardiac workload in presence of a critical coronary stenosis (demand ischemia), coronary occlusion (supply ischemia) or a combination of both. It is complicated by cardiac arrhythmias and deterioration of function of ischemic myocardium and results in an increased load and dilatation of non-ischemic myocardium. Cardiac protection in acute myocardial ischemia can be related to preservation of coronary blood flow, function of ischemic and non-ischemic myocardium or prevention of cardiac arrhythmias. In control animals and humans, ACE-inhibitors have no major effect on coronary blood flow. Myocardial ischemia raises plasma-renin-activity, angiotensin I-conversion by passage through coronary circulation, and plasma-angiotensin-II-concentrations. ACE-inhibitors and angiotensin-II-receptor blockers increase coronary blood flow during myocardial ischemia. Other mechanisms (bradykinin potentiation) may be involved. We found a potentiation of the coronary dilatory effect of the neuropeptide neurotensin (which is probably mediated by prostaglandins) by ACE-inhibitor. ACE-inhibitor may delay infarct development in animal experiments and improve function of ischemic myocardium. The importance of early dilatation of non-ischemic myocardium is unknown and it is unclear whether it may be prevented by an ACE-inhibitor as was shown for late dilatation. Studies on the effect of ACE-inhibitors in exercise-induced angina pectoris are controversial. An antiischemic and coronary dilatory effect has been shown by invasive studies in patients. A preliminary study in unstable angina pectoris was positive. Beneficial hemodynamic and antiarrhythmic effects (as well as excessive hypotension, however) have been shown in patients with acute myocardial infarction.
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PMID:[Possibilities of ACE inhibitor therapy in acute myocardial ischemia]. 186 31

Acute myocardial ischemia was induced by reducing the lumen of the anterior descending branch of the left coronary artery in 32 mongrel dogs. Following 60 min of ischemia, 16 animals were infused perfluorine carbon emulsion (10 ml/kg) and 16 were given saline. Alteration in hemodynamics, myocardial contractility, coronary blood flow, as well as pH and pO2 in the ischemic area were examined. The analysis of the results showed that carbon tetrafluoride emulsion, in contrast to saline, substantially increased coronary blood flow and oxygen supply in the ischemic area decreased myocardial ischemic and reperfusion lesion, improved hemodynamic parameters and myocardial contractility.
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PMID:[An emulsion of fluorocarbons as a protective agent against myocardial ischemia]. 188 39

Acute myocardial ischemia provokes sensitization of the adenylyl cyclase system. This sensitization can be differentiated in a receptor-specific and an enzyme-specific sensitization. The receptor-linked sensitization is characterized by an increase of beta-adrenergic receptors in the plasma membranes after 15 mins of global ischemia (49.8 +/- 3.6 to 67 +/- 6 fmol/mg protein) followed by a further increase (89 +/- 4 fmol/mg protein) after 50 min of ischemia in isolated perfused hearts. Concomitantly functionally coupled receptors which are able to bind the beta-agonist with high affinity, increased by 32% after 15 min and by 57% after 50 min of ischemia. The affinities of the receptors for their agonists or their antagonists remain unchanged. Maximally isoproterenol-stimulated adenylyl cyclase activity rose from 66 +/- 7 to 101 +/- 10 pmol cAMP/min/mg protein after 15 min of global ischemia indicating the beta-receptor-specific sensitization of the beta-adrenergic system. This sensitization was followed by a gradual decline of the adenylyl cyclase activity after 30 and 50 min of global ischemia. Additionally, 15 min of myocardial ischemia induced an enzyme-linked sensitization of the adenylyl cyclase activity as indicated by an increase of the forskolin-stimulated activity by about 25% (300 +/- 20 vs 378 +/- 25 pmol cAMP/min/mg protein). In contrast after 50 min of ischemia the total adenylyl cyclase activity declined (232 +/- 24 pmol cAMP/min/mg protein) despite the persistent increase of beta-adrenergic receptors in the plasma membranes. These data demonstrate that the enzyme-specific sensitization is only transient. The early sensitization and late inactivation of the adenylyl cyclase activity occurred independently of receptor activation and could not be prevented by beta-blockade (10(-6) M alprenolol). Cyanide perfusion (1 mM), used to block energy metabolism, lead to energy depletion similar to acute myocardial ischemia. This resulted in an increase of functionally coupled receptors with a time course comparable to that of global ischemia. Additional perfusion with desensitizing concentrations of the beta-agonist isoproterenol did not induce uncoupling or internalization of beta-adrenergic receptors in cyanide treated hearts, suggesting that the rise in functionally coupled receptors is due to a redistribution in part caused by the abolition of continuous receptor internalization. In contrast, the enzyme-linked sensitization is independent of cellular localization of the beta-adrenergic receptors. The increased activity was carried by the enzyme even after partial purification with solubilization and wheat germ affinity chromatography. These data suggest an ischemia-induced, covalent modification of the adenylyl cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dual sensitization of the adrenergic system in early myocardial ischemia: independent regulation of the beta-adrenergic receptors and the adenylyl cyclase. 196 11

Acute myocardial ischemia leads to a gradual increase in beta-adrenergic receptors at the cell surface. This increase occurs rapidly after onset of global ischemia (15 minutes) and persists even after prolonged periods of global ischemia. This alteration can be observed both in vivo and in vitro in isolated perfused hearts. Several groups have previously shown that ischemia induces a local release of endogenous catecholamines. Here, we show that these endogenous catecholamines are sufficiently high to induce receptor desensitization with internalization of beta-adrenergic receptors in normal hearts. In acute myocardial ischemia, however, agonist-promoted internalization and functional uncoupling of beta-adrenergic receptors is abolished. Consequently, the balance of internalization and externalization of receptors is shifted toward an increase in functionally coupled receptors at the cell surface. Similarly, but inconsistently, the density of alpha 1-adrenergic receptors in the plasma membrane is increased in acute myocardial ischemia. In regard to function, the increase of coupled beta-adrenergic receptors leads to an augmented responsiveness of the adenylyl cyclase system to beta-adrenergic stimulation. This receptor-specific sensitization is superimposed by a transient increase of total adenylyl cyclase activity in the very early phase of global ischemia (0-20 minutes). The enhanced activity of adenylyl cyclase to direct stimulation is tightly associated with the partially purified enzyme, suggesting a covalent modification of the enzyme molecule. However, after prolonged periods (greater than 30 minutes) of global ischemia, the ischemia-induced enzyme-specific sensitization is displaced by a general reduction in enzyme activity, both in vivo and in vitro. The persistent sensitization at the receptor level then meets an unresponsive adenylyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adrenergic receptors and sensitization of adenylyl cyclase in acute myocardial ischemia. 216

Acute myocardial ischemia maintained for 30 and 60 min with subsequent reperfusion did not induced alterations in the cyclic AMP-mediated phosphorylation capacity of phospholamban and troponin I. Inotropic stimulation of the normal heart with 0.1/uM isoprenaline for 2 min resulted in a simultaneous P-incorporation into phospholamban and troponin I to 44.4 +/- 7.5 pmoles P/mg protein and 42.4 +/- 2.9 pmoles P/mg protein, respectively, assayed by a standardized back-phosphorylation procedure. The adrenergic responsiveness, however, was markedly reduced in the time course of ischemia. After an ischemic period of 60 min the adrenergic-stimulated phosphorylation of phospholamban was diminished to 41 per cent of the control value, whereas the increase of troponin I phosphorylation was completely lost. This differential effect can be discussed in terms of the existence of cytosolic compartments for cA, possessing different lability to ischemic injury of cardiac cells. After post-ischemic reperfusion the isoprenaline responsiveness of the phosphorylation of phospholamban and troponin I was found to be normal demonstrating a reversibility at the level of two important regulator proteins, if the transient ischemia do not exceed 60 min period.
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PMID:Phosphorylation of phospholamban and troponin I in the ischemic and reperfused heart: attenuation and restoration of isoprenaline responsiveness. 252 30


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