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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 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

The cardiopulmonary effects of constant-flow ventilation were investigated in dogs with normal heart function (control-phase, n = 14) and after development of acute myocardial ischaemia (ischaemia phase, n = 14). Heated, humidified and oxygen-enriched air was continuously delivered with an inspiratory flow rate of 1.21.kg-1.min-1 via two catheters positioned within each mainstem bronchus. Continuous positive pressure ventilation with a positive end-expiratory pressure of 0.5 kPa (5 cmH2O) was used as a reference. During control, neither continuous positive pressure ventilation nor constant-flow ventilation showed impairment of cardiopulmonary performance. Oxygenation and CO2 removal were more efficiently achieved by continuous positive pressure ventilation (P less than or equal to 0.05). Acute myocardial ischaemia was induced by occlusion of the left anterior descending (LAD) coronary artery; measurements during the ischaemia phase were performed 60 min following LAD occlusion. Myocardial ischaemia resulted in moderate changes of cardiac output, left ventricular end-diastolic pressure and dP/dtmax. Both modes of ventilation were well tolerated in the ischaemia phase, and cardiovascular performance revealed no significant differences between continuous positive pressure ventilation and constant-flow ventilation. Haemodynamic parameters could be more precisely assessed during constant-flow ventilation. Oxygenation deteriorated, but hypoxaemia did not occur in any animal and CO2 elimination remained unchanged. It is concluded that 'non-conventional' ventilation by continuous intrabronchial gas flow maintains adequate gas exchange with no adverse effects on haemodynamics in dogs with acute myocardial ischaemia. Constant-flow ventilation may be advantageous in the experimental setting to study cardiac function without cyclic heart-lung interaction due to airway pressure alterations.
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PMID:Cardiopulmonary effects of constant-flow ventilation in experimental myocardial ischaemia. 178 43

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 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

To examine the effects of acute myocardial ischemia and reperfusion on regional coronary vasodilator (or flow) reserve, peak reactive hyperemic blood flow following a 10 s occlusion was obtained in dogs subjected to circumflex (Cx) coronary artery occlusion for 1 h followed by reperfusion for 1 h. Acute myocardial ischemia resulting from Cx artery occlusion-reperfusion caused an attenuation in peak reactive hyperemic Cx flow (mean +/- S.E., from 215 +/- 29% to 87 +/- 17%, P less than or equal to 0.001). Acetylcholine-induced increase in Cx flow was also significantly (P less than or equal to 0.01) attenuated following Cx occlusion-reperfusion. These alterations were not observed in the left anterior descending (LAD) coronary artery, which was not subjected to occlusion. Pre-treatment of four dogs with indomethacin inhibited prostaglandin release (P less than or equal to 0.01), but did not affect peak reactive hyperemic coronary flow or acetylcholine-induced increase in coronary flow before or after occlusion-reperfusion. Histopathology revealed extensive myocardial neutrophil infiltration in the Cx-supplied region compared to the LAD-supplied region. Myocardial myeloperoxidase activity, an index of neutrophil infiltration, was also increased in the Cx compared to the LAD region (P less than or equal to 0.02). Myocardial neutrophil accumulation and myeloperoxidase activity were similar in the control and indomethacin-treated animals. These observations suggest that acute myocardial ischemia resulting from coronary artery occlusion-reperfusion impairs coronary vasodilator reserve in anesthetized dogs. This impairment, which was not modified by prostaglandin inhibition, may be related to the loss of endothelium-derived relaxing factor and/or decreased microvascular cross-sectional area resulting from capillary plugging by neutrophils.
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PMID:Reduction in coronary vasodilator reserve following coronary occlusion and reperfusion in anesthetized dog: role of endothelium-derived relaxing factor, myocardial neutrophil infiltration and prostaglandins. 285 Oct 52

Acute myocardial ischemia followed by protracted asynergy and subsequent resolution was defined as reversible ischemic myocardial damage. The purpose of this study was to confirm the existence of this entity and to illustrate the clinical features. The subjects consisted of 26 patients with typical acute myocardial ischemia who satisfied the above definition, and serial changes in left ventricular wall motion were observed by two-dimensional echocardiography. The left ventricle was divided into 11 segments and the movement was scored according to the dynamic behavior of each segment by five points ranging from normal (0) to dyskinesis (4), and evaluated semiquantitatively using the total score sum as the total asynergy score. Compared to the initial value, this score decreased to 57% after one week, 38% in two weeks, 22% in three weeks and 17% in four weeks. The asynergy persisted 23.7 +/- 13.5 days and ranged from two days to three months. The peak CPK ranged from 32 to 561 IU (mean 212 +/- 157 IU). Coronary arteriography revealed undisturbed flow of the responsible artery in both acute and chronic phases including four cases of successful PTCR. Comparison of the electrocardiographic changes and asynergy showed that diminished R wave amplitude, ST segment elevation and inverted T waves are frequently associated with persistence of asynergy, extensive asynergy can even occur in cases without a diminished R wave or abnormal Q wave and when asynergy resolves, ST segments tend to return to the baseline, but T wave inversion commonly persists. A transient Q wave was observed in 38% of the patients examined. The electrocardiogram became normal in an average of 111.3 +/- 75 days. In conclusion, there is a subgroup of reversible asynergy among cases of unstable angina pectoris or subendocardial infarction. The mechanism for this may be myocardial "stunning" following transient transmural ischemia. Recognition of this fact seems very important in the diagnosis and treatment of acute myocardial ischemia.
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PMID:[Reversible ischemic myocardial damage: clinical observation using two-dimensional echocardiography]. 365 11

To evaluate whether myocardial texture changes resulting from acute ischemia can be visualized with satisfactory spatial resolution, short axis compound echo images (CEI) (B-scan) were obtained from 12 excised canine hearts in vitro. Seven had myocardial ischemia produced by open chest ligation of the left anterior descending coronary artery (LAD) for 15-30 min prior to excision. The CEI were constructed by compounding 60 simple linear B-scans. Hearts were sectioned after scanning, and gross morphological changes were recorded. Microscopic comparison between grossly abnormal and normal regions were recorded. The CEI from the ischemic group revealed altered myocardial texture seen as bright coarsely granular echoes in the regions normally perfused by the ligated LAD artery. Corresponding anatomic sections revealed increased redness in these regions. Microscopically these regions revealed interstitial and intercellular edema as compared to the normal regions. Acute myocardial ischemia can be visualized in CEI and these regions have significantly increased backscatter, decreased attenuation, and decreased speed of ultrasound relative to normal regions in the same hearts. Myocardial edema is probably responsible for these changes.
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PMID:Echocardiographic visualization of acute myocardial ischemia--in vitro study. 379 86


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