Quantitative MR measurements of regional and global left ventricular function and strain after intramyocardial transfer of VM202 into infarcted swine myocardium.
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.
Dept. of Radiology and Biomedical Imaging, UCSF, 513 Parnassus Ave., HSW207B, San Francisco, CA 94134-0628, USA.
Marcus
M
Carlsson
Nael F
NF
Osman
Philip C
PC
Ursell
Alastair J
AJ
Martin
Maythem
M
Saeed
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013318:Stroke Volume; D013552:Swine; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor