I11111

0 5 10 15 20 25 Relative infarct weight (%) Fig. 4. Correlation curve between relative infarct weight and cTnT concentration at 96 h after the onset of infarction in canine model of nonreperfused AMI. (Adapted from ref. 34.)

markers is most readily available and commonly performed using markers such as CK, CK-MB-isoform, hydroxybutyrate dehydrogenase, or lactic dehydrogeanase.

Ideally, infarct sizing involves serial collection of cardiac markers and integration of the area under the curve of a plot of enzyme activity or protein concentration vs time. Such calculations produce an estimate of the quantity of infarcted tissue that correlates to anatomic estimates of infarct size made at autopsy (30). In clinical practice, peak levels of markers ofnecrosis and, less frequently, area under the time release curve of CK-MB obtained from repetitive, serial sampling are used to estimate infarct sitze (31). However, missing the true peak value is associated with a high likelihood of underestimation of infarct size (32). For cardiac markers that exhibit the washout phenomenon, infarct-sizing estimates are inaccurate when reperfusion of occluded coronary arteries is successful (33). In addition, the quality of reperfusion and duration of ischemia may influence the washout of the marker.

The introduction of cardiac troponin may overcome some of the limitations of this approach because troponin T or I is exclusively cardiac specific and is almost completely bound to the contractile apparatus (6). With troponin T, only the initial rapid peak, which is owing to release of the cytoplasmic pool, depends on the reperfusion status, whereas the second late peak, which is owing to degradation from the contractile apparatus, is independent of the reperfusion status (6,9). Several animal experiments have documented the usefulness ofcTnT measurements for estimation ofinfarct size. In a canine nonreperfused experimental infarct model, Remppis et al. (34) plotted serial plasma cTnT concentrations against histochemical infarct size. They found a close relationship between area under the cTnT time release curve or peak cTnT concentrations and histological infarct size at autopsy (Fig. 4). However, the need for repetitive sampling over a long period and the possibility of incomplete recovery are costly and not practical in clinical routine. To provide a cost-effective and feasible protocol, receiver operating analysis was performed to compare the efficacy of a fixed-time protocol vs serial sampling algorithms. In the canine model, a single cTnT concentration measured at 96 h after the onset of ischemia correlated closely with histological infarct size. In humans, cTnT concentrations at 72 h after infarction were found to correlate with scintigraphically detected (thallium) infarct

cTnT Concentration

Fig. 5. Correlation curve between infarct weight measured by contrast-enhanced MRI and cTnT concentration at 96 h after onset of infarction in rabbit model of nonreperfused AMI (unpublished data).

cTnT Concentration

Fig. 5. Correlation curve between infarct weight measured by contrast-enhanced MRI and cTnT concentration at 96 h after onset of infarction in rabbit model of nonreperfused AMI (unpublished data).

Fig. 6. Correlation between area ofperfusion defect on myocardial contrast echocardiography and troponin T on admission (A) and at 96 h (B) after onset of symptoms in patients with an ACS without ST-elevation. (Adapted from ref. 37.)

size (35). Panteghini et al. (36) found that a single-point cTnT measurement at 72 h after MI correlated with infarct size measured from gated SPECT.

In a rabbit model of nonreperfused MI, areas of late hyperenhancement seen with contrast-enhanced MRT closely correlated with troponin T concentrations at 96 h after the onset of infarct (Fig. 5). This close relationship confirmed using myocardial contrast echocardiography in a series of 100 patients with ACS without ST-elevation (37) (Fig. 6).

Similarly, a correlation was found between early peak values oftroponin I and the volume of infarcted nonreperfused myocardium as detected by contrast-enhanced MRT (38). Not unexpectedly, the investigators failed to demonstrate a relationship between infarct size and troponin I peak within the first 24 h after the onset of infarct, proving again that early troponin release is strongly influenced by cytoplasmic release during reperfusion (6,9).

MRT is an excellent method for quantifying myocardial infarct of <1 g and is superior to SPECT for detection of subendocardial myocardial infarcts (39,40). Forthcoming clinical studies are likely to be useful in establishing the applicability of troponin for estimation of infarct size in reperfused and nonreperfused MI. In human studies, magnetic resonance imaging (MRI) may serve as the "gold standard" against which troponin concentrations may be plotted.

Given the different release kinetics of troponin I and the heterogeneity of troponin I assays, troponin I must be validated separately and for each troponin I assay.

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