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Review
. 2010 Dec;17(6):1107-15.
doi: 10.1007/s12350-010-9292-5.

Dysinnervated but viable myocardium in ischemic heart disease

James A Fallavollita  1 , John M Canty Jr
Affiliations
Review

Dysinnervated but viable myocardium in ischemic heart disease

James A Fallavollita et al. J Nucl Cardiol. 2010 Dec.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Viable, denervated myocardium after myocardial infarction. These PET polar tomograms and wire diagrams of the left ventricle from a subject in the PAREPET study illustrate the relative uptake of the sympathetic nerve tracer 11C-meta-hydroyxephedrine (HED, left images) and the viability tracer 18F-2-deoxyglucose (FDG, right images). Tracer retention is color coded from maximum activity in red to minimum activity in blue. The extent of sympathetic denervation extends beyond that of the inferolateral infarct. In addition to denervation at the periphery of the infarct, there is apical extension due to interruption of the sympathetic nerves that course across the heart from the base to the apex. A and Ant, anterior wall; S and Sep, interventricular septum; L and Lat, lateral wall; I and Inf, inferior wall.
Figure 2
Figure 2
Progression of HED defects during the development of hibernating myocardium in chronically instrumented pigs. Preserved HED uptake at 1 month confirmed that LAD instrumentation did not affect regional sympathetic nerve function. The polar maps at 2 and 3 months after instrumentation were serially obtained in the same animal. These studies show a clear progression from a small, localized defect in the apex at 2 months (relative uptake, LAD/normal = .76) to a larger and more severe defect 3 months after instrumentation (relative uptake = .50). The increasing size and severity of the HED defects parallels the changes in stenosis severity as this model progresses from chronically stunned to hibernating myocardium. Modified from Luisi et al. Reprinted with permission of the Society of Nuclear Medicine, Inc. Ant, anterior; Lat, lateral, Inf, inferior; Sep, septum.
Figure 3
Figure 3
HED images in pigs with normal, hibernating, and subendocardially infarcted myocardium. Standard imaging views demonstrate homogeneous HED uptake in a normal control animal. In contrast, there is a severe and extensive HED defect involving the LAD distribution in a pig with hibernating myocardium, consistent with partial sympathetic denervation. In an animal with subendocardial infarction in the LAD distribution, the defect in HED uptake is actually less severe and extensive than that in hibernating myocardium. Modified from Luisi et al. Reprinted with permission of the Society of Nuclear Medicine, Inc. SA, short axis; HLA, horizontal long axis; VLA, vertical long axis).
Figure 4
Figure 4
Partial sympathetic denervation in porcine hibernating myocardium. These photomicrographs illustrate the immunohistochemical staining of tyrosine hydroxylase (yellow) in a sham control pig (left) and an animal with hibernating myocardium (right). Sympathetic nerves (arrows) are present in hibernating myocardium, although they are not as abundant as in control myocardium. These images are consistent with the reduced (but not absent) functional responses to sympathetic stimulation and candidate sympathetic nerve protein expression, confirming partial sympathetic denervation in pigs with hibernating myocardium.
Figure 5
Figure 5
HED imaging before and after therapeutic intervention in pigs with hibernating myocardium. Each pair of images is from a pig with hibernating myocardium serially imaged before and 1 month after therapy with either pravastatin (A) or percutaneous coronary intervention (PCI, B). The polar tomograms illustrate that the size and severity of the HED defects remained remarkably stable between the two studies, despite the fact that each therapy resulted in significant improvement in regional and global function in pigs with hibernating myocardium.- Representative reconstructed short axis (SA), vertical long axis (VLA), and horizontal long axis (HLA) views are also shown. Reprinted from Fallavollita et al. S, interventricular septum; L, lateral wall; I, inferior wall.
Figure 6
Figure 6
Extent of the MIBG defect correlates with area at risk during acute coronary occlusion. These polar tomograms were obtained from a patient with an acute anterior myocardial infarction. The risk area was quantified with 99mTc-sestamibi prior to reperfusion with percutaneous coronary intervention, and infarct size was documented from repeat imaging 1 week later. The defect in sympathetic nerve function assessed with MIBG was significantly larger than the area of infarction and was almost identical to the original extent of myocardial ischemia. Figure source: Dr. Markus Schwaiger. Ant, anterior; Lat, lateral; Inf, inferior; Sep, septum.
Figure 7
Figure 7
Regional differences in HED are greater than MIBG in hibernating myocardium. PET imaging demonstrated a 48 ± 3% reduction in HED retention in hibernating myocardium (black bars) as compared to the remote, normally perfused region (gray bars) of chronically instrumented pigs. In contrast, the regional difference in MIBG retention was only 25 ± 3% despite the fact that activity was quantified by ex vivo counting. This significant difference in relative retention (LAD/remote) was the result of improved specificity of HED due to less non-specific uptake than MIBG. Modified from Luisi et al. *P < 0.05 vs remote. †P < 0.05 vs MIBG. Reprinted with permission of the Society of Nuclear Medicine, Inc.
Figure 8
Figure 8
Representative patterns of resting flow, viability, and sympathetic innervation in subjects with ischemic cardio-myopathy. The tomograms within each row are from the same subject. The integrated volumes of infarction and dysinnervation as a percentage of the left ventricle are to the right of each image. The upper row (A) shows a subject with an extensive area of viable dysinnervated myocardium involving the anterior, lateral, and inferior myocardium. In (B), the inferolateral defect in sympathetic innervation is primarily the result of a large infarct with a concomitant reduction in resting flow and metabolic viability. The lower row (C) shows a mixed pattern of abnormal sympathetic innervation involving both viable and nonviable myocardium. Reprinted from Fallavollita et al. With permission of Elsevier, copyright 2006. A, anterior; L, lateral; I, inferior, S, septal.
Figure 9
Figure 9
Mismatch between pre-synaptic and post-synaptic sympathetic functions may predict mortality. These short-axis PET images of pre-synaptic norepinephrine transport function (HED) and post-synaptic β-adrenergic receptor density (11C-CGP 12177) were obtained in a patient with NYHA Class III ischemic heart failure. Extensive mismatch between the two tracers is most evident in the apical and basal segments. The box and whisker plot (right graph) shows the ratio between β-receptor density and norepinephrine (NE) transport function for patients with ischemic heart failure (N = 13) as compared to normal controls (N = 19). The four patients who died within 15 months of imaging had significantly greater mismatch ratios than the nine survivors. The boxes span the 25th to 75th percentiles with the 95% confidence intervals delineated by the error bars. Modified from Link and Caldwell and reprinted with permission of MacMillan Publishers Ltd. Nature Clinical Practice Cardiovascular Medicine, copyright 2008.
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