Early ReportVisualisation of cell death in vivo in patients with acute myocardial infarction
Introduction
In patients with an acute myocardial infarction, cardiomyocyte death occurs in the infarct area, leading to loss of contractile function of the heart. Several animal studies have shown that ischaemia of the heart, followed by reperfusion, results in a substantial loss of cardiomyocytes through apoptosis (programmed cell death).1, 2, 3 This observation implies that cardiomyocytes in the infarct area might be rescued if efficient blockade of the cell-death programme is possible.4 In cardiac biopsy samples obtained from patients with an acute myocardial infarction, DNA fragmentation—a hallmark of apoptotic cell death—has been shown.5, 6 However, since cardiac biopsy samples are necessary to show DNA fragmentation, information about the extent and time-frame of programmed cell death is difficult to obtain after an acute myocardial infarction. Hence, new therapeutic strategies that target myocardial cell death are difficult to assess owing to the lack of knowledge about the dynamics of cell death early after reperfusion.
One of the earliest events in programmed cell death is the externalisation of phosphatidylserine from the inner leaflet of the plasma membrane to the outer leaflet.7 Externalisation of phosphatidylserine is closely related to activation of important components of the cell death programme, and occurs, at least in vitro, downstream from the release of cytochrome C by mitochondria and activation of executioner caspases.8, 9 We and others have shown that labelled annexin-V, which has a high affinity for phosphatidylserine, is a specific and reliable tool for the detection of apoptotic cells under various conditions, including ischaemia and reperfusion in the murine heart.10, 11, 12, 13 On the basis of these studies, we decided to test radionuclide imaging with technetium-99m-labelled human recombinant annexin-V to visualise cardiac cell death after reperfusion therapy in patients with an acute myocardial infarction.
Section snippets
Patients
Seven patients with a first acute myocardial infarction who presented within 6 h of the onset of symptoms, were candidates for the study. The diagnosis of an acute myocardial infarction was made by electrocardiographic criteria and confirmed by biochemical detection of cardiac enzyme release. Six patients underwent primary percutaneous transluminal coronary angioplasty (PTCA) of the infarct-related vessel, resulting in thrombolysis in myocardial infarction (TIMI) III flow. In one patient, after
Results
We studied five men and two women (table). The mean age was 55·9 years (SD 6·6). In six of the seven patients, increased uptake of Tc-99m-labelled annexin-V in the infarct area was seen on early and late SPECT images. Figure 1 shows an example of increased annexin-V uptake in the anteroseptal area of the late SPECT of a patient with an acute anterior-wall myocardial infarction (patient 1). Increased annexin-V uptake was seen in the anteroseptal area on the images obtained 22 h after injection.
Discussion
Animal studies have shown detection of cell death in vivo with Tc-99m-labelled annexin-V and nuclear imaging. Blankenberg and colleagues reported detection of cell death in the heart in a cardiac transplant model in rats.14 Increased uptake of annexin-V was seen in transplanted hearts, which correlated with the in-vitro detection of DNA fragmentation by terminal deoxynucleotidylmediated-dUTP nick-end labelling (TUNEL). We have previously shown that reperfusion of the infarct area of the mouse
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