• Journal of Chest Surgery
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• v.38 no.5 s.250
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• pp.323-334
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• 2005

Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.95-103
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• 1996

Reverse redistribution(RRD) refers to a perfusion defect that develops or becomes more evident on rest imaging compared with the stress imaging. This phenomenon was not uncommonly noted on myocardial perfusion single photon emission computed tomography (SPECT). However, the clinical significance and pathophysiological mechanism of RRD were unclear. The aim of this study was to evaluate the incidence and clinical significance of RRD on either dipyridamole T1-201 or Tc-99m MIBI myocardial perfusion SPECT. RRD was defined as ${\geq}10%$ decrease in relative T1-201 and Tc-99m MIBI uptakes on rest images compared to the stress images or as an appearance of new perfusion defects on rest images. It was observed in both T1-201 (44/463, 9.5%) and Tc-99m MIBI (124/999, 12.4%) myocardial SPECTs similarly, with an overall incidence of 11.5%(168/1462). Many apparent)y unrelated disease groups showed the finding: post-revascularization(53.9%), coronary artery disease(24.6%), myocardial infarction(12.3%), and those with normal coro-nary arteries (9.2%). Clinical and angiographic characteristics of 65 consecutive patients who underwent coronary arteriography in 168 patients who had RRD on myocardial perfusion SPECT were reviewed. Tc-99m MIBI was used in 44 patients, and T1-201 was used in 21 patients. Of the 81 myocardial segments analyzed which showed RRD, 32 segments(39.5%) were in septum, 24(29.5%) in inferior wallL, 12(14.8%) in anterior wall, 7(8.7%) in apex and 6(7.4%) in lateral wall. There was no clear association between RRD and coronary arterial stenosis or Presence of collateral circulations. Ventriculographical wall motion was evaluated in 27 regions with RRD; it was normal in 12 regions, hypokinetic in 12 regions and dyskinetic in 3 regions. In 14 of 21 patients who showed RRD on T1-201 myocardial SPECT, T1-201 reinjection was performed immediately after the 3-4 hour redistribution studies. Ten of 14 (71.4%) showed enhanced T1-201 activity(${\geq}10%$ increased) after reinjection. We conclude that RRD is not related to mode of stress or radiopharmaceuticals. RRD might represent many inhomogeneous pathophysiological processes.