Author + information
- John F. O'Sullivan, MD, PhD⁎,
- Anne-Laure Leblond, PhD⁎,
- John O'Dea, MD,
- Ivalina Hristova, BS,
- Sujith Kumar, DMRIT,
- Kenneth Martin, PhD,
- Arun H.S. Kumar, DVM, PhD and
- Noel M. Caplice, MD, PhD⁎ ()
- ↵⁎Centre for Research in Vascular Biology, Biosciences Institute, University College Cork, College Road, Cork, Ireland
To the Editor
Early percutaneous coronary intervention (PCI) and reperfusion of obstructed epicardial arteries have improved patient survival after myocardial infarction (MI), but downstream, microvascular obstruction (MVO) remains a significant negative predictor after acute infarct PCI (1). Recently, it has been suggested that dynamic contrast-enhanced multidetector computed tomography (MDCT) may be equally effective as magnetic resonance imaging (MRI) in predicting MVO in the clinical setting (2), but evidence validating this contention is scant. Nitrite ions are microvascular vasodilators, and have been demonstrated to reduce MRI-defined MVO, and to improve endocardial blood flow in a large-animal MI model, verified using the accepted gold standard: thioflavin S exclusion (TSE) to define MVO and microsphere analysis to measure regional blood flow (RBF) (3).
The purpose of this study was: 1) to correlate putative MVO contrast attenuation patterns (hypoenhancement area on MDCT image) with MVO derived from ex vivo TSE and RBF assessment; and 2) to determine whether nitrite-induced dynamic changes in MVO could be equally detected using RBF assessment and MDCT image analysis.
Sixteen female, 25 kg to 30 kg, Landrace pigs (of which 12 survived: 6 in the saline group; 6 in the nitrite group) underwent experimental MI by balloon occlusion of the mid left anterior descending artery for 90 min followed by reperfusion for 2 h (4). After balloon deflation, MDCT and microsphere delivery were performed at the same time point. Areas of hyperenhancement and hypoenhancement were determined using a 5-min delayed enhancement scan. The number of microspheres detected in each region of the heart, corrected for aortic blood flow, provided RBF for that region for each condition (5). Nitrite diluted in saline (0.2 μmol · min−1 · kg−1), or an equal volume of saline, was delivered in the mid left anterior descending artery at the onset of reperfusion. Twenty-four hours after MI, animals underwent repeat MDCT and microspheres administration. An injection of 20 ml 4% thioflavin S was made into the left ventricle (LV) 2 min before sacrifice. The heart was then explanted and sliced into short-axis slices 1 cm thick. A 2,3,5-triphenyltetrazolium chloride (TTC)-2% solution was used to delineate the infarct area.
The TTC- and TSE-defined regions for microspheres sampling identified distinct differences in RBF between remote, TTC-defined infarct, and TSE-defined MVO areas 24 h after MI at basal, mid, and apical ventricular levels: infarct and MVO areas had significantly reduced RBF (Fig. 1A and 1B), validating TTC- and TSE-defined areas. Microspheres analysis also showed a significant increase in RBF in remote and MVO (p < 0.05) regions in the nitrite-treated group compared with the saline-treated group (n = 6 pigs per group) (Figs. 1A and 1C), confirming nitrite beneficial effects on MVO after MI. Combined hypoenhancement and hyperenhancement areas on MDCT (putative infarct zone) correlated well with TTC-defined infarct area (r2 = 0.74, n = 12 pigs, p < 0.004) (Figs. 1A and 1D). However, MDCT hypoenhancement (putative MVO area) did not correlate well with TSE-defined MVO area (r2 = 0.42, n = 9 pigs, p = 0.21) (Figs. 1A and 1E). The MDCT imaging analysis after MI did not show any significant difference between saline- and nitrite-treated groups in terms of percent changes in infarct size (combined hypoenhancement and hyperenhancement/LV: −15.6 ± 6.9% and −10.0 ± 15.7%, respectively; p = 0.76) or hyperenhancement/LV ratio (43.1 ± 36.4% and 27.3 ± 36%, respectively; p = 0.77) and hypoenhancement/LV ratio (−38.7 ± 15.9% and −46.0 ± 18.5%, respectively; p = 0.78; n = 6 pigs per group) (Fig. 1F).
This study demonstrates that MDCT hypoenhancement area after MI does not accurately predict MVO area, suggesting limitations of MDCT for the detection of MVO. Thus, reduced RBF (impairing contrast penetration) may not be the only determinant of hypoenhancement on MDCT. Moreover, in this study, MDCT did not predict dynamic changes in MVO, suggesting that, as well as not being a good imaging modality to detect MVO changes after therapeutic intervention, it may also be suboptimal in detecting dynamic MVO responses to vasodilators. Our data do, however, confirm prior suggestions that combined hypoenhancement and hyperenhancement area on MDCT is a reliable measure of infarct area. In terms of imaging infarction, a significant advantage of MDCT over MRI is that signal density values are unique and determined by the physical properties of individual constituents of the heart resulting from direct attenuation of X-rays by iodine molecules, not an indirect measure resulting from gadolinium-induced alterations of water proton relativity, as on MRI. Therefore, MDCT may be, hypothetically at least, a more accurate modality for measuring infarct size. Our data have clinical implications, suggesting caution when using CT to detect MVO in post-MI patients.
↵⁎ Drs. O’Sullivan and Leblond contributed equally to this work.
Please note: Grants were provided by Molecular Medicine Ireland (R12699-JOS), Science Foundation Ireland (R11482-NMC, RFP06-NMC), and Health Research Board, Dublin, Ireland (R11831-NMC); National Biophotonics and Imaging Platform, Ireland; the Irish Government's Programme for Research in Third Level Institutions, Cycle 4, and Ireland's EU Structural Funds Programmes 2007 to 2013. The authors have reported they have no relationships relevant to the contents of this paper to disclose.
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