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

To investigate excitation-contraction coupling in stunned myocardium, intracellular free calcium concentration [( Ca2+]i) was measured before and after ischemia in perfused hearts using gated 19F NMR and the Ca2+ indicator 5F-BAPTA. Maximal Ca(2+)-activated force was also measured in parallel experiments. Stunned myocardium was created by reperfusion after 15 min global ischemia at 37 degrees C in isolated ferret hearts. In stunned myocardium, peak [Ca2+]i was paradoxically higher than that in control, but maximal Ca(2+)-activated pressure was lower in stunned hearts. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to a decrease in maximal Ca(2+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The role of intracellular calcium overload in the pathogenesis of stunned myocardium was also investigated. Time-averaged 19F NMR measurements directly revealed the increase in [Ca2+]i during ischemia and in the early phase of reperfusion. The strategies to prevent Ca overload during reperfusion with modified reperfusate succeeded in preserving contractile function. Transient Ca overload without ischemia induced by different causes, i.e., high [Ca]0 perfusion, ventricular fibrillation or treatment with adriamycin, also produced contractile dysfunction that outlasted the interventions themselves. Thus, we propose that transient Ca overload during ischemia and early reperfusion initiates long-lasting contractile dysfunction in stunned myocardium.
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PMID:Pathophysiology and pathogenesis of contractile failure in stunned myocardium. 194 93

Myocardium that is not functioning may be dead (infarct or scar), viable but stunned (postischemic ventricular dysfunction), viable but hibernating (chronic low flow state), or acutely ischemic. Stunned myocardium has clearly been documented (a) in experimental studies of brief coronary artery occlusion followed by reperfusion, and (b) in myocardial infarct models in which early reperfusion salvages viable tissue. Recent clinical studies have confirmed the existence of stunned myocardium in humans. Evidence supporting the concept of hibernating myocardium comes from clinical studies in which patients with chronic low flow ischemia exhibit improvement in left ventricular function (sometimes immediately) following revascularization.
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PMID:Stunned and hibernating myocardium. 203 55

Stunned myocardium can be produced by repeated short episodes of ischemia. Histochemical and ultrastructural abnormalities such as sarcomere lengthening and myofiber thinning have been noted in myocardium soon after the onset of ischemia and have been attributed to the mechanical stretching that occurs during ventricular systole. To test whether mechanical forces alone could produce the residual dysfunction seen in stunned myocardium, regional dyskinesia was produced in open chest dogs by six repeated intracoronary infusions of either potassium chloride, 0.2 mEq/min for 2.5 minutes, or lidocaine, a 10 mg bolus followed by 1 to 3 mg/min for 5 minutes. These dogs were matched with dogs that had six repeated coronary occlusions of 2.5 and 5 minutes' duration, respectively. Regional function was analyzed using fractional systolic shortening and the load-independent end-systolic pressure-length relation. Both potassium chloride and lidocaine produced regional dyskinesia that was similar to the dyskinesia produced by coronary occlusion. Although regional ventricular function after repeated coronary occlusions remained significantly reduced, function returned completely to normal within 5 minutes after the last drug-induced dyskinesia. In conclusion, regional dysfunction produced by potassium chloride and lidocaine does not produce residual dysfunction despite mechanical forces during systole similar to those seen during coronary occlusion.
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PMID:Effect of repeated episodes of drug-induced ventricular dyskinesia on subsequent regional function in the dog: comparison with myocardial stunning produced by repeated coronary occlusions. 358 22

The effect of recurrent periods of ischemia on the myocardium was investigated in 15 open-chest dogs. Ischemia was produced by 3 minutes of proximal occlusion of the left anterior descending coronary artery. Each occlusion was followed by reperfusion of 3 minutes duration. Forty occlusions with a total of 120 minutes of ischemia were performed, and regional function (sonomicrometry) as well as high energy phosphates (needle biopsies) were determined at the end of the 5th, 20th, and 40th period of ischemia and reperfusion. The first periods of ischemia had a cumulative effect both on regional postischemic function (44% and 59% respectively of preischemic control after 20 occlusions) and on the ATP content, but with increasing number of occlusions the additive effects became smaller (ATP reduction/mumol/g w w/per occlusion). The ATP breakdown per occlusion was diminished with increasing number of periods of ischemia, and no significant adenosine was measured in the ischemic myocardium. Higher than normal postischemic creatine phosphate levels (9.1 mumol/g w w at the 40th reperfusion vs. 6.7 mumol/g w w control) indicated a functioning oxidative phosphorylation in the presence of an ATP utilization problem at the sarcomere level, because indicators of the cellular energy level (energy charge, free energy change of ATP hydrolysis) quickly normalized during reperfusion. Stunned myocardium is therefore not a problem of energy supply but rather of energy utilization. Reduced ATP utilization and regional dysfunction are the expressions of the same cellular defect which resides either in the ATP-splitting contractile apparatus or in the electromechanical coupling. Contractile dysfunction during reperfusion protects the heart against subsequent periods of ischemia because ATP turnover is reduced.
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PMID:Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels. 377 16

Stunned myocardium is defined as postischemic dysfunction of viable myocardium. This phenomenon was initially described in animal models of brief ischemia followed by reperfusion, but is becoming increasingly recognized in clinical situations. One of these situations is ventricular dysfunction following coronary artery bypass surgery. Several clinical reports have demonstrated depressed ventricular function in the initial hours after coronary artery bypass surgery: this dysfunction is usually resolved within 24 to 48 hours, and does not appear to be dependent upon alterations in preload, afterload, or temperature. New therapies for improving postischemic myocardial function following cardiopulmonary bypass are under investigation.
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PMID:Clinical evidence for stunned myocardium after coronary artery bypass surgery. 806 26

Dysfunctional myocardium may be viable in patients with acute myocardial infarction. Although viable but dyssynergic myocardium may be recognized a posteriori by the occurrence of functional recovery, prospective identification of the actual myocardial state is more important for optimal therapeutic management. Echocardiography during pharmacological interventions is a useful clinical tool, as changes in regional myocardial thickening may be continuously monitored. Stunned myocardium exhibits contractile dysfunction after an ischemic episode despite normalized or near normalized myocardial flow, but stunned myocardium retains contractile reserve. It may be identified by improvement in contractility during a low dose dobutamine infusion in segments showing a mismatch between normal perfusion and reduced contractility. In regions of viable but stunned myocardium corresponding to an artery with reduced coronary flow reserve, contractility may improve at low dose dobutamine infusion and may later deteriorate at high dose, indicating the presence of jeopardized myocardium. Ischemia at a distance observed with dobutamine indicates the presence of multivessel coronary artery disease. These informations are useful for clinical decision making.
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PMID:Comparison of approaches in the assessment of myocardial viability and follow-up of PTCA/CABG. The role of echocardiography. 840 39

Timely coronary reperfusion as treatment for acute myocardial infarction reduces myocardial infarct size, improves left ventricular function and survival. There is still concern that at the time of reperfusion, a further injury occurs to the myocardium. Theoretically, if this "reperfusion injury" could be treated and eliminated, the outcome for patients with myocardial infarction might further improve. The concept of reperfusion injury is closely tied to the concept that oxygen radicals generated at the time of reperfusion cause tissue damage. There are four basic forms of reperfusion injury. Lethal reperfusion injury is described as myocyte cell death due to reperfusion itself rather than to the preceding ischemia. This concept continues to be controversial in both experimental animal and clinical studies. Vascular reperfusion injury refers to progressive damage to the vasculature over time during the phase of reperfusion. Manifestations of vascular reperfusion injury include an expanding zone of no reflow and a deterioration of coronary flow reserve. This form of reperfusion injury has been documented in animal models and probably occurs in humans. Stunned myocardium refers to postischemic ventricular dysfunction of viable myocytes and probably represents a form of "functional reperfusion injury." This phenomenon is well documented in both animal models and humans. Reperfusion arrhythmias represent the fourth form of reperfusion injury. They include ventricular tachycardia and fibrillation that occur within seconds to minutes of restoration of coronary flow after brief (5 to 15 min) episodes of myocardial ischemia. True reperfusion arrhythmias occur in only a small percentage of patients receiving thrombolytic therapy for acute myocardial infarction and are not a sensitive indicator for successful reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does reperfusion injury exist in humans? 842 22

Stunned myocardium produced by 1 hour of critical coronary artery stenosis was evaluated for alteration in regional mechanical function and overall oxidative and fatty acid metabolism by positron emission tomography (PET) in chronically instrumented dogs. Twenty-seven dogs, chronically instrumented for measurements of left ventricular pressure and regional myocardial wall thickening in normal and ischemic zones, were subjected to a 1-hour period of myocardial ischemia produced by graded left circumflex coronary artery stenosis, resulting in minimal residual flow. Mean transmural myocardial flow during 1-hour coronary stenosis decreased to 0.34 +/- 0.04 ml/min per gram in the ischemic zones (normal zone transmural flow, 0.96 +/- 0.10 ml/min per gram). Systolic wall thickening in the ischemic zone was almost completely abolished (-97 +/- 4%). On reperfusion, systolic wall thickening immediately resumed but remained depressed. Progressive recovery was noted with time. At 24 hours, systolic wall thickening was still depressed (-20 +/- 6%, p < 0.01). At 1 week, wall thickening had completely recovered and was no longer significantly different from the control condition. In addition, the absence of necrosis at the site of wall thickness measurements was confirmed at autopsy in all dogs. No abnormalities were found by electron microscopy in four dogs undergoing myocardial biopsies at the time of PET studies. Dynamic PET studies using [1-11C]acetate tracer (performed at 6 hours, 1 week, and 2 weeks after reperfusion) and [1-11C]palmitic acid tracer (performed at 6 hours, 12 hours, 24 hours, 1 week, and 2 weeks after reperfusion) allowed the computation of regional tissue time-activity curves in different regions of interest at different times during follow-up. Despite full reperfusion, abnormal [1-11C]acetate and [1-11C]palmitic acid kinetics were observed in the posterior segments, previously subjected to ischemia, as evidenced by a significant decrease in the slope of the early 11C clearance curve component. Repeat PET studies revealed progressive normalization of overall oxidative metabolism and fatty acid metabolism, which paralleled the time course of recovery of mechanical function. Thus, myocardial ischemia, produced by 1-hour coronary artery stenosis, followed by full reperfusion is associated with a prolonged period of postischemic mechanical and metabolic dysfunction. This transient reduction in oxygen delivery induced a prolonged impairment in fatty acid beta-oxidation as well as a reduction in overall oxidative metabolism despite full reoxygenation. A similar time course for recovery of function and metabolism was observed.
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PMID:Recovery of regional contractile function and oxidative metabolism in stunned myocardium induced by 1-hour circumflex coronary artery stenosis in chronically instrumented dogs. 844 76

Effect of verapamil post-treatment (0.2 mg/kg bolus, followed by 0.01 mg/kg/min infusion) on the functional and metabolic changes of the heart after a brief regional ischemia (20 min) followed by 1 hr of reperfusion was studied in open-chest pentobarbitone anaesthetized dogs. In control dogs 1 hr of reperfusion failed to cause any improvement of depressed myocardial contractility (LVdP/dtmax and LVEDP) caused by 20 min of ischemia, which confirmed the earlier reported phenomenon of 'Stunned Myocardium'. Myocardial ischemia caused a significant loss of high-energy phosphate (HEP) content of the affected myocardium (ATP decreased by 60% and CP decreased by 75% of non-ischemic level). Following 1 hr of reperfusion, myocardial ATP was not replenished, though creatine phosphate became near normal. When verapamil was administered just before reperfusion, it showed a profound beneficial effect on the incidence of fatal reperfusion arrhythmias. At the end of 1 hr of reperfusion in this group, the recovery of the myocardial contractility was incomplete, but a significant replenishment of the myocardial HEP content was observed. Thus verapamil post-treatment can prevent reperfusion-induced myocardial injury but functional recovery may be delayed due to the drug's inherent direct myocardial depressant effect.
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PMID:Effect of verapamil post-treatment in myocardial reperfusion injury. 850 Aug 27

Stunned myocardium may occur after an episode of prolonged or transient ischemia. This phenomenon can occur in a variety of patient groups including medical, surgical, neurologic, and cardiac patients. In the stunned myocardium, myocardial contractility is temporarily depressed, causing symptoms similar to those of cardiogenic shock. When critical care nurses are familiar with the clinical characteristics and risk factors of stunned myocardium, they can start the appropriate interventions and left ventricular function returns to normal within days with no residual hypokinesis. Critical care nurses play a key role in assisting surgeons and other noncardiac physicians in the diagnosis and care of the patient with stunned myocardium.
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PMID:Stunned myocardium: theoretical mechanisms of injury. 869 89


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