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Quantitative MR measurements of regional and global left ventricular function and strain after intramyocardial transfer of VM202 into infarcted swine myocardium

Carlsson, Marcus LU ; Osman, Nael F. ; Ursell, Philip C. ; Martin, Alastair J. and Saeed, Maythem (2008) In American Journal of Physiology - Heart and Circulatory Physiology 295(2). p.522-532
Abstract

Previous studies have shown the beneficial effects of the hepatocyte growth factor (HGF) gene on myocardial perfusion and infarction size but not on the regional strain in relationship to global left ventricular function. A noninvasive magnetic resonance (MR) study was performed to determine the effect of a new HGF gene, VM202, expressing two isoforms of HGF, on regional and global left ventricular function. Pigs (8/group) were divided into three groups: 1) controls without infarction; 2) reperfused, infarcted controls; and 3) infarcted, treated (1 h after reperfusion) with VM202 injected at eight sites. Cine, tagging, and delayed enhancement MR images were acquired at 3 and 50 ± 3 days after infarction. At 50 days, ejection fraction in... (More)

Previous studies have shown the beneficial effects of the hepatocyte growth factor (HGF) gene on myocardial perfusion and infarction size but not on the regional strain in relationship to global left ventricular function. A noninvasive magnetic resonance (MR) study was performed to determine the effect of a new HGF gene, VM202, expressing two isoforms of HGF, on regional and global left ventricular function. Pigs (8/group) were divided into three groups: 1) controls without infarction; 2) reperfused, infarcted controls; and 3) infarcted, treated (1 h after reperfusion) with VM202 injected at eight sites. Cine, tagging, and delayed enhancement MR images were acquired at 3 and 50 ± 3 days after infarction. At 50 days, ejection fraction in infarcted, treated animals increased (38 ± 1% to 47 ± 2%, P < 0.01) to the level of controls without infarction (52 ± 1%, P = 0.16) but decreased in infarcted controls (41 ± 1% to 37 ± 1%, P < 0.05). Two-dimensional strain improved in remote, peri-infarcted, and infarcted myocardium. Furthermore, the infarction size was smaller in infarcted, treated animals (7.0 ± 0.5%) compared with infarcted controls (13.2 ± 1.6%, P < 0.05). Histopathology showed a lack of hypertrophy in myocytes in peri-infarcted and remote myocardium and the formation of islands/peninsulas of myocytes in infarcted, treated animals but not in infarcted controls. In conclusion, the plasmid HGF gene caused a near complete recovery of ejection fraction and improved the radial and circumferential strain of remote, peri-infarcted, and infarcted regions within 50 days. These beneficial effects may be explained by the combined effects of a speedy and significant infarct resorption and island/peninsulas of hypertrophied myocytes within the infarcted territory but not by compensatory hypertrophy. The combined use of cine and tagging MR imaging provides valuable information on the efficacy of gene therapy.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gene therapy, Heart failure, Infarction, Magnetic resonance imaging, Remodeling
in
American Journal of Physiology - Heart and Circulatory Physiology
volume
295
issue
2
pages
522 - 532
publisher
American Physiological Society
external identifiers
  • pmid:18539758
  • scopus:52449100395
ISSN
0363-6135
DOI
10.1152/ajpheart.00280.2008
language
English
LU publication?
no
id
1f8fd734-117f-4ed5-86fd-0b2ea74a4e64
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519203/
date added to LUP
2019-05-14 15:09:05
date last changed
2020-01-13 01:46:41
@article{1f8fd734-117f-4ed5-86fd-0b2ea74a4e64,
  abstract     = {<p>Previous studies have shown the beneficial effects of the hepatocyte growth factor (HGF) gene on myocardial perfusion and infarction size but not on the regional strain in relationship to global left ventricular function. A noninvasive magnetic resonance (MR) study was performed to determine the effect of a new HGF gene, VM202, expressing two isoforms of HGF, on regional and global left ventricular function. Pigs (8/group) were divided into three groups: 1) controls without infarction; 2) reperfused, infarcted controls; and 3) infarcted, treated (1 h after reperfusion) with VM202 injected at eight sites. Cine, tagging, and delayed enhancement MR images were acquired at 3 and 50 ± 3 days after infarction. At 50 days, ejection fraction in infarcted, treated animals increased (38 ± 1% to 47 ± 2%, P &lt; 0.01) to the level of controls without infarction (52 ± 1%, P = 0.16) but decreased in infarcted controls (41 ± 1% to 37 ± 1%, P &lt; 0.05). Two-dimensional strain improved in remote, peri-infarcted, and infarcted myocardium. Furthermore, the infarction size was smaller in infarcted, treated animals (7.0 ± 0.5%) compared with infarcted controls (13.2 ± 1.6%, P &lt; 0.05). Histopathology showed a lack of hypertrophy in myocytes in peri-infarcted and remote myocardium and the formation of islands/peninsulas of myocytes in infarcted, treated animals but not in infarcted controls. In conclusion, the plasmid HGF gene caused a near complete recovery of ejection fraction and improved the radial and circumferential strain of remote, peri-infarcted, and infarcted regions within 50 days. These beneficial effects may be explained by the combined effects of a speedy and significant infarct resorption and island/peninsulas of hypertrophied myocytes within the infarcted territory but not by compensatory hypertrophy. The combined use of cine and tagging MR imaging provides valuable information on the efficacy of gene therapy.</p>},
  author       = {Carlsson, Marcus and Osman, Nael F. and Ursell, Philip C. and Martin, Alastair J. and Saeed, Maythem},
  issn         = {0363-6135},
  language     = {eng},
  month        = {08},
  number       = {2},
  pages        = {522--532},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Heart and Circulatory Physiology},
  title        = {Quantitative MR measurements of regional and global left ventricular function and strain after intramyocardial transfer of VM202 into infarcted swine myocardium},
  url          = {http://dx.doi.org/10.1152/ajpheart.00280.2008},
  doi          = {10.1152/ajpheart.00280.2008},
  volume       = {295},
  year         = {2008},
}