Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first?

Kloner, Robert A.; Rude, Robert E.; Carlson, Nancy; Maroko, Peter R.; DeBoer, Laurence W.V.; Braunwald, Eugene

doi:10.1161/01.cir.62.5.945

Cited by 466 publications

(186 citation statements)

References 15 publications

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“…Each dog was anesthetized with sodium pentobarbital, 25 mg/kg, intubated, ventilated with a Harvard respirator and maintained with 0.25% halothane. An arterial line was placed in the left femoral artery to measure arterial pressure and for withdrawal of a reference blood sample during radioactive microsphere injection.…”

Section: Experimental Preparationmentioning

confidence: 99%

The time course and characterization of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.

Higginson¹,

Beanlands²,

Nair³

et al. 1983

Circulation

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SUMMARY We quantitated hemorrhage associated with reperfusion after varying periods of myocardial ischemia and examined the flow characteristics that accompany reperfusion hemorrhage. Anesthetized dogs were reperfused after 2, 6 or 24 hours of circumflex occlusion. A control group underwent coronary occlusion without reperfusion. Radioactive microspheres were injected before and 5 minutes and 24 hours after reperfusion. The papillary muscles were analyzed for hemoglobin content, flow during myocardial ischemia and flow early and 24 hours after reperfusion. Myocardial creatine kinase activity was assayed to determine the severity of myocardial necrosis in the papillary muscles.Hemorrhage into the posterior papillary muscle was dependent upon the duration of coronary artery occlusion. Posterior papillary hemoglobin averaged 14 mglg in the 2-hour group, 28 mg/g in the 6-hour group and 36 mg/g in the group reperfused 24 hours after occlusion, compared with 8.7 mg/g in the control group. Myocardial hemorrhage was associated with severe depression in myocardial CK and marked depression in flow to the ischemic area (i.e., collateral flow) during the occlusion. Early reflow averaged 112 ml/min/100 g in the 2-hour group, 61 ml/min/100 g in the 6-hour group and only 5.8 ml/min/lO0 g in the 24-hour group. Therefore, myocardial hemorrhage induced by reperfusion of the acutel ischemic myocardium is associated with severe ischemia during occlusion and severe myocardial necrosis, but does not depend upon the magnitude of early reflow. Myocardial hemorrhage may occur even though initial reflow values are markedly decreased.REPERFUSION of the acutely ischemic myocardium might appear to be an easy way of reversing myocardial ischemia and limiting the eventual extent of myocardial infarction. Reperfusion after brief periods of myocardial ischemia does prevent the development of infarction, and reperfusion after 3 hours of myocardial ischemia may limit the eventual infarct size.'4 The benefits of reperfusion, however, are controversial.Some studies have demonstrated an exacerbation of ventricular arrhythmias, accelerated morphologic changes of ischemia and worsening metabolic function.5-10 The deleterious effects of reperfusion are often associated with myocardial hemorrhage.45' 7 9 This supposedly occurs because of irreversible damage to the microcirculation and the extravasation of blood on reperfusion. Hemorrhage on reperfusion has also been described in man, particularly after long periods of intraoperative myocardial ischemia. Coronary artery bypass surgery in the setting of acute myocardial infarction is being performed more and more frequently and streptokinase-induced reperfusion is receiving widespread acceptance."-14 Thus, reperfusion in the setting of myocardial infarction is a clinical reality and broader knowledge is required about the phenomenon of hemorrhage upon reperfusion.Accordingly, we examined the phenomenon of myocardial hemorrhage upon reperfusion of the acutely ischemic myocardium. We studied the frequency o...

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Section: Experimental Preparationmentioning

confidence: 99%

The time course and characterization of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.

Higginson¹,

Beanlands²,

Nair³

et al. 1983

Circulation

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“…With this rationale, thrombaspiration, protection devices and coronary vasodilators are used to reduce peri-interventional reperfusion injury [9]. However, vice versa there may be primary damage to cardiomyocytes which only subsequently progresses to coronary microvascular damage, as seen in animal models with mechanical occlusion/reperfusion of virgin coronary arteries without a culprit lesion [14]. Whether cardiomyocyte damage per se is causal for subsequent coronary microvascular damage or both are consequences of the same fundamental pathomechanism, e.g., excessive reactive oxygen species formation, remains unclear.…”

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confidence: 99%

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

2013

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Timely reperfusion is the only way to rescue ischemic myocardium from impending infarction. However, reperfusion also adds a component of injury to that incurred during ischemia and thus contributes to final infarct size [6,20,28]. It appears that all conditioning strategies which delay infarct size development and/or reduce infarct size act through attenuation of such reperfusion injury [7]. Apart from its contribution to cardiomyocyte necrosis, reperfusion is frequently also characterized by the development of areas of no-reflow within the previously ischemic myocardium [10]. Evidence for microvascular no-reflow by angiography or MRI despite successfully reopened epicardial coronary arteries in patients with myocardial infarction is associated with impaired recovery of ventricular function and worse survival [19].The coexistence of infarcted cardiomyocytes and areas of coronary microvascular no-reflow in reperfused myocardium is well established [13]; however the underlying mechanisms are not really clear. Several mechanisms can initiate no-reflow in previously ischemic myocardium: (a) embolization of particulate atherosclerotic debris from the culprit lesion into the coronary microcirculation, both after mechanical or thrombolytic reopening of epicardial coronary arteries The analysis of temporal and spatial relationships between infarcted myocardium and no-reflow is largely limited by methodological restraints. By definition, infarcted myocardium and no-reflow are confined to the previously ischemic area at risk. This appears trivial, but when analyzed by clinical imaging technology, the area at risk is often not determined or not clear. Slow/no-flow phenomena outside the area at risk may also occur but have a different underlying pathophysiology, e.g., reflex-mediated coronary vasoconstriction [4,8]. Myocardial infarction develops progressively during ischemia, and a separate component of irreversible injury is added during early reperfusion; the relative contribution of infarction which develops during ischemia and during reperfusion varies and depends on the duration of ischemia [3]. Even with gold standard technology (TTC staining) in the experiment, infarcted tissue is only recognized as such after several hours of reperfusion, and no distinction between myocardium infarcting during ischemia and during reperfusion is possible. No-reflow, as evidenced by lack of endothelial staining by thioflavin in the experiment [13], develops rapidly during early reperfusion and progresses over time [1,22,23]. Most studies indicate that no-reflow areas are This comment refers to the article available at

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“…[5][6][7] The failure to achieve adequate tissue perfusion is referred to as the no-reflow phenomenon, which occurs as a result of microvascular damage or intramyocardial edema induced by ischemia. 8,9 On angiograms, the no-reflow phenomenon is defined as substantial coronary antegrade flow reduction (less than Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) without epicardial mechanical obstruction. 10 Recent studies have shown that angiographic contrast velocity after successful percutaneous coronary intervention (PCI), as defined by the TIMI criteria, predicts poor left ventricular (LV) functional recovery and a higher risk of cardiac mortality.…”

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Coronary Flow Velocity Pattern Immediately After Percutaneous Coronary Intervention as a Predictor of Complications and In-Hospital Survival After Acute Myocardial Infarction

et al. 2002

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Background— Recently, it was reported that the degree of microvascular injury and left ventricular functional recovery during the chronic period can be predicted after treatment of the infarct-related artery based on the coronary flow velocity (CFV) pattern assessed using a Doppler guidewire. The aim of this prospective study was to examine whether the CFV pattern may predict complications and in-hospital survival after acute myocardial infarction (AMI). Methods and Results— The study population consisted of 169 consecutive patients with a first anterior AMI successfully treated with percutaneous coronary intervention (PCI). We examined the CFV pattern immediately after PCI using a Doppler guidewire. In accordance with previous findings, we defined severe microvascular injury as a diastolic deceleration time ≤600 ms and the presence of systolic flow reversal. Patients were divided into two groups: those without severe microvascular injury (n=118; group 1) and those with severe microvascular injury (n=51; group 2). All of the patients who had cardiac rupture were in group 2. Congestive heart failure (CHF) was observed more frequently in group 2 than in group 1 (53% versus 8%, P <0.001). The in-hospital cardiac mortality rate was significantly higher in group 2 than in group 1 (18% versus 0%, P <0.001). Nine patients in group 2 died, 5 patients because of CHF and 4 patients because of cardiac rupture. Conclusions— These findings suggest that the CFV pattern is an accurate predictor of the presence or absence of complications and of in-hospital survival after AMI.

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Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first?

Cited by 466 publications

References 15 publications

The time course and characterization of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.

The time course and characterization of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

Coronary Flow Velocity Pattern Immediately After Percutaneous Coronary Intervention as a Predictor of Complications and In-Hospital Survival After Acute Myocardial Infarction

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