Effect of Scar Compaction on the Therapeutic Efficacy of Anisotropic Reinforcement Following Myocardial Infarction in the Dog.

Cardiac restraint devices have been used following myocardial infarction (MI) to limit left ventricular (LV) dilation, although isotropic restraints have not been shown to improve post-MI LV function. We have previously shown that anisotropic reinforcement of acute infarcts dramatically improves LV function. This study examined the effects of chronic, anisotropic infarct restraint on LV function and remodeling. Hemodynamics, infarct scar structure, and LV volumes were measured in 28 infarcted dogs (14 reinforced, 14 control). Longitudinal restraint reduced 48-h LV volumes, but no differences in LV volume, function, or infarct scar structure were observed after 8 weeks of healing. All scars underwent substantial compaction during healing; we hypothesize that compaction negated the effects of restraint therapy by mechanically unloading the restraint device. Our results lend support to the concept of adjustable restraint devices and suggest that scar compaction may explain some of the variability in published studies of local infarct restraint.

Comparison of quantitative wall-motion analysis and strain for detection of coronary stenosis with three-dimensional dobutamine stress echocardiography.

BACKGROUND: Quantitative analysis of wall motion from three-dimensional (3D) dobutamine stress echocardiography (DSE) could provide additional diagnostic information not available from qualitative analysis. In this study, we compare the effectiveness of 3D fractional shortening (3DFS), a measure of wall motion computed from 3D echocardiography (3DE), to strain and strain rate measured with sonomicrometry for detecting critical stenoses during DSE. METHODS: Eleven open-chest dogs underwent DSE both with and without a critical stenosis. 3DFS was measured from 3DE images acquired at peak stress. 3DFS was normalized by subtracting average 3DFS during control peak stress (∆3DFS). Strains in the perfusion defect (PD) were measured from sonomicrometry, and PD size and location were measured with microspheres. RESULTS: A ∆3DFS abnormality indicated the presence of a critical stenosis with high sensitivity and specificity (88% and 100%, respectively), and ∆3DFS abnormality size correlated with PD size (R(2) = 0.54). The sensitivity and specificity for ∆3DFS were similar to that for area strain (88%, 100%) and circumferential strain and strain rate (88%, 92% and 88%, 86%, respectively), while longitudinal strain and strain rate were less specific. ∆3DFS correlated significantly with both coronary flow reserve (R(2) = 0.71) and PD size (R(2) = 0.97), while area strain correlated with PD size only (R(2) = 0.67), and other measures were not significantly correlated with flow reserve or PD size. CONCLUSION: Quantitative wall-motion analysis using ∆3DFS is effective for detecting critical stenoses during DSE, performing similar to 3D strain, and provides potentially useful information on the size and location of a perfusion defect.

Myocardial uptake of 7'-(Z)-[(123)I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses.

BACKGROUND: There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[(125)I]iodorotenone ((125)I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of (123)I-ZIROT in an intact large-animal model. METHODS AND RESULTS: The (123)I-ZIROT was administered during adenosine A(2A) agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, (123)I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. (123)I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At (123)I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial (123)I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or (99m)Tc-sestamibi from previous studies using a similar model. Furthermore, the (123)I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09). CONCLUSIONS: The ability of (123)I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.

Molecular imaging identifies regions with microthromboemboli during primary angioplasty in acute coronary thrombosis.

UNLABELLED: Microthromboemboli (MTE) may contribute to the no-reflow phenomenon in acute myocardial infarction (AMI) either spontaneously or after primary percutaneous transluminal coronary angioplasty (PTCA). We hypothesized that myocardial MTE in acute coronary syndromes can be identified on imaging by in vivo (99m)Tc labeling of the coronary thrombus with a compound that binds to the glycoprotein IIb/IIIa present on activated platelets (DMP-444). METHODS: Fifteen dogs underwent left anterior descending coronary artery (LAD) injury in to produce thrombus, whereas 5 control dogs had LAD ligation. Before recanalization, the risk area (RA) and myocardial blood flow (MBF) were measured, and in vivo thrombus labeling was performed using (99m)Tc-labeled DMP-444. Nine of the 15 LAD injury dogs had occlusive thrombus on angiography and underwent PTCA. MBF measurements were repeated 30 and 60 min after recanalization, and (99m)Tc autoradiography (hot spot imaging) was performed ex vivo to determine the extent and magnitude of MTE. RESULTS: The ratio of hot spot size to RA size was higher in the 9 LAD injury dogs with thrombus compared with the 6 dogs with no thrombus (90% +/- 22% vs. 42% +/- 16%; P = 0.005). In control dogs, this ratio was significantly lower (29% +/- 11%; P = 0.05). (99m)Tc activity within the RA was higher in 8 of the 15 coronary injury dogs with AMI compared with those without AMI (1.8 +/- 0.48 vs. 1.24 +/- 0.22; P = 0.02). CONCLUSION: MTE can be detected and quantified after primary PTCA. The infarct size is proportional to the magnitude and extent of MTE, indicating that MTE may contribute to the AMI. Thus, in vivo thrombus labeling during reperfusion may provide important information in patients with AMI that may lead to better adjuvant therapy during PTCA.

Further insights into the no-reflow phenomenon after primary angioplasty in acute myocardial infarction: the role of microthromboemboli.

We tested the hypothesis that when acute coronary occlusion is caused by thrombus, part of the no-reflow phenomenon may result from spontaneous or coronary angioplasty-induced microthromboemboli, and that this phenomenon may be partly or wholly reversible. Accordingly, a thrombus was created in the left anterior descending coronary artery of 6 dogs and was labeled in vivo with (99m)Tc-DMP-444 that binds to the IIb/IIIa platelet receptor. Angioplasty was then performed to obtain thrombolysis in myocardial infarction grade-3 flow. Myocardial contrast echocardiography was performed 15 and 60 minutes after recanalization to define perfusion defect size. (99m)Tc-autoradiography and infarct size (IS) measurement were performed postmortem. An additional 5 dogs with coronary artery ligation followed by reperfusion served as control animals. These dogs also underwent myocardial contrast echocardiography and in vivo labeling with (99m)Tc-DMP-44. (99m)Tc uptake was significantly higher in the reperfused bed in dogs with thrombus compared with control dogs (2.7 +/- 0.9 vs 1.4 +/- 0.3 counts/pixel(-1)/min(-1), P =.01) indicating the presence of microthromboemboli. Perfusion defect size early (15 minutes) after recanalization was smaller than the hot spot on autoradiography and overestimated IS in dogs with thrombus. Perfusion defect size decreased with time and was closer to IS 60 minutes after recanalization. The dogs with thrombi demonstrated larger IS/risk area ratios compared with the 5 control dogs (46 +/- 6% vs 27 +/- 12%, P =.04). We conclude that part of the no-reflow phenomenon seen after angioplasty in acute coronary thrombosis is a result of microthromboemboli and is mostly reversible. No reflow late after reperfusion is a result of tissue necrosis. The thrombus burden also affects ultimate IS.