Use of exercise technetium-99m sestamibi SPECT imaging to detect residual ischemia and for risk stratification after acute myocardial infarction

The clinical presentation, electrocardiographic findings, and technetium-99m sestamibi single-photon emission computed tomography (SPECT) imaging results of 134 consecutive patients who underwent nuclear exercise testing within 14 days of an acute myocardial infarction (AMI) were correlated with cardiac events over a 15 +/- 10-month follow-up. Whereas only 23 patients (17%) had chest pain and 31 (23%) had ischemic ST-segment depression during exercise, 94 (70%) had ischemia on SPECT (p < 0.001). On follow-up, 13 patients experienced a cardiac event: 7 were rehospitalized for unstable angina, 3 had recurrent AMI, and 3 died of cardiac causes. Ischemia on the sestamibi images identified 11 of these patients (85%), whereas chest pain identified only 3 (23%, p = 0.006), and electrocardiographic ischemia identified only 4 (31%, p = 0.017). The presence of either ischemia as seen on SPECT or defects in multiple vascular territories identified 12 patients (92%) with an event, including all who had cardiac death. By Cox regression analysis of clinical, stress, and image parameters, the number of ischemic defects on SPECT was the only significant correlate of a future event (chi-square = 4.62, p = 0.03), and patients with > or = 3 reversible sestamibi defects had an event rate of 38%. The extent of ischemia as seen on nuclear imaging remained a strong correlate (p = 0.008) of an event in the 54 patients (40%) who had received thrombolytic therapy. Thus, exercise technetium-99m sestamibi SPECT after AMI frequently reveals residual ischemia, and is better than clinical data, symptoms, and stress electrocardiographic data in identifying patients who will have a subsequent cardiac event.     

Ligands with affinity to specific sequences of DNA base pairs. X. Synthesis and binding of netropsin analogs, containing a chelating copper ion peptide, with DNA

An analogue of netropsin has been synthesized consisting of two N-propylpyrrolcarboxamide units linked covalently to a copper-chelating tripeptide Gly-Gly-L-His by means of two and three glycine residues. Binding to DNA and synthetic polynucleotides of netropsin analogue containing three glycine residues between Gly-Gly-L-His tripeptide and the N-end of netropsin analogue (His-Nt) has been studied. It is shown that this netropsin analogue chelates a copper ion with 1:1 stoichiometry, similar to a free Gly-Gly-L-His peptide. It is found that this netropsin analogue occupies 3 to 4 base pairs upon binding to poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers, irrespective of whether it binds in Cu(2+)-ligated or unligated forms. Binding constants and binding site sizes have been calculated for netropsin analogue complexes with DNA, poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers at the [Cu2+]/[His-Nt] ratio equal to 0 and 1.0. In the three-component system including His-Nt and Cu(2+)-His-Nt, cooperative effects are recognized which can be explained by heterodimer generation on interaction of His-Nt and Cu(2+)-His-Nt at adjacent binding sites.