Quantification of myocardial injury produced by temporary coronary artery occlusion and reflow with technetium-99m-pyrophosphate.

Abstract

Previously, technetium-99m-stannous pyrophosphate (99mTc-PPi) has been used to localize and estimate the size of myocardial infarcts in animals after permanent coronary artery occlusion. This study tested the hypothesis that 99mTc-PPi accurately sizes myocardial infarctions produced by temporary coronary artery occlusion and reflow in dogs. Three groups of dogs were studied: group A underwent 3 hr of occlusion followed by 2 hr of reperfusion, with 99mTc-PPi injected 10 min after reflow (n = 10); group B underwent 3 hr of occlusion followed by 2 hr of reperfusion, with 99mTc-PPi injected 90 min after reflow (n = 11); and group C underwent 3 hr of occlusion followed by reflow with 99mTc-PPi injected at 10 min and again at 48 hr after reflow (n = 5). Myocardial slices from group A and B dogs were imaged in vitro. Group C dogs were imaged with single photon-emission computed tomography (SPECT) in vivo, and myocardial slices were imaged in vitro at the conclusion of the study. The extent of myocardial infarction was defined with triphenyltetrazolium chloride (TTC) staining, and coronary blood flow was estimated with radioactive microspheres. In addition, transmural myocardial tissue samples were taken from the center of the myocardial infarction, the lateral portion of the myocardial infarction, the normal myocardium adjacent to the lateral aspect of the infarcts, and from the normal myocardium and counted for 99mTc-PPi activity. A significant correlation was found between infarct size determined by areas of increased 99mTc-PPi uptake and that estimated from TTC staining for both group A (r = .89) and group B animals (r = .98). However, the intercepts and slopes relating estimates of infarct size from 99mTc-PPi uptake and TTC staining indicated that 99mTc-PPi overestimated size of infarction when injected early after reflow (group A), especially that of small infarcts (.5 g). Results in group C dogs confirmed that, in the same dogs, estimates of infarct size were smaller when 99mTc-PPi was injected relatively late as compared with early after reperfusion. Thus, 99mTc-PPi injected 90 min or later after reperfusion provides an excellent means to identify and size myocardial infarcts produced by temporary coronary artery occlusion and reflow in this canine preparation. 99mTc-PPi uptake early, but not late, after reperfusion probably occurs in some myocardial cells that are severely injured but viable after reperfusion, and possibly in cells with excess cytosolic calcium that recover with longer periods of reperfusion. Circulation 75, No. 3, 611-617, 1987. REPERFUSION early after acute myocardial infarction is presently being evaluated as a potential means to reduce infarct size and mortality, and preserve regional ventricular function.' Evaluation of reperfu-

Imaging of Acute Myocardial Infarction and Reperf usion

“…These authors hypothesized that in clinical imaging, and depending on the threshold level required for tracer detection, there could be a very marked discrepancy between scintigraphic estimates of infarct size with 99mTc PYP and "'In Ab, particularly in reperfused infarcts. This is supported by the data of Jan sen et al [12] who demonstrated that scintigraphic infarct size with 99mTc PYP is significantly larger when 99mTc PYP is injected after 3 h of reperfusion rather than after 48 h of reperfusion, following a 3-hour coronary occlu sion. This observation is consistent with 99mTc uptake in injured but viable myocytes.…”

Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with reperfusion therapy

“…The use of infarct size as a surrogate outcome in phase II clinical trials as a preliminary estimate of treatment effect is predicated on the previously demonstrated relationship between CK-MB and infarct size [4,5,7,8], and between infarct size and meaningful clinical outcomes [8-22]. Thus, it is important to define the most accurate and reliable method to estimate infarct size using CK-MB measures as surrogate endpoints in clinical trials of treatment effect.…”

“…The relationship between creatine kinase (CK)-MB measured in the blood and infarct size has been well-established through both pathological and imaging correlations [1-8]. Furthermore, infarct size, measured by release of CK-MB for example, is associated with short- and long-term cardiovascular complications such as cardiac death, reinfarction, congestive heart failure, stroke and unstable angina requiring hospitalization [9-19].…”

“…Furthermore, infarct size, measured by release of CK-MB for example, is associated with short- and long-term cardiovascular complications such as cardiac death, reinfarction, congestive heart failure, stroke and unstable angina requiring hospitalization [9-19]. Infarct size determined by other methods of quantification, such as single-photon emission computed tomography, left ventricular angiography, echocardiogram and contrast-enhanced magnetic resonance imaging, have also been associated with subsequent clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) [8,20-22]. …”

Circulating myosin light chain I levels after coronary reperfusion: A comparison with myocardial necrosis evaluated from single photon emission computed tomography with pyrophosphate

“…Several studies have described an overestimation of infarct size calculated by Tc-99m PYP in preparations of temporary coronary occlusions followed by reperfusion, but Jansen reported that SPECT imaging with adequate threshold makes possible accurate localization and determination of infarct size when Tc-99m PYP was injected 90 min or more after reflow. 12 So SPECT with Tc-99m PYP is attractive for the evaluation of acute infarct size.…”