COMPLETE REVERSAL OF ISCHEMIC WALL-MOTION ABNORMALITIES BY COMBINED USE OF GENE-THERAPY WITH TRANSMYOCARDIAL LASER REVASCULARIZATION

SAYEEDSHAH U MANN MJ MARTIN J GRACHEV S REIMOLD S LAURENCE R DZAU V COHN LH

U. Sayeedshah et al., COMPLETE REVERSAL OF ISCHEMIC WALL-MOTION ABNORMALITIES BY COMBINED USE OF GENE-THERAPY WITH TRANSMYOCARDIAL LASER REVASCULARIZATION, Journal of thoracic and cardiovascular surgery, 116(5), 1998, pp. 763-768

29

INGLESE

Article

Cardiac & Cardiovascular System",Surgery

Journal of thoracic and cardiovascular surgery → ACNP

0022-5223

116

5

1998

763 - 768

ISI

0022-5223(1998)116:5<763:CROIWA>2.0.ZU;2-A

Introduction: Transmyocardial laser revascularization is believed to i nduce an angiogenic response within ischemic myocardium, We evaluated transgene expression in the setting of transmyocardial laser revascula rization and hypothesized that intramyocardial injection of plasmid DN A encoding the gene for vascular endothelial growth factor could enhan ce the revascularization achieved by transmyocardial laser revasculari zation, resulting in improved cardiac function. Methods: Ten Yorkshire pigs had carbon dioxide-transmyocardial laser revascularization or ac upuncture sites with injections of an expression plasmid encoding the gene for beta-galactosidase with or without HVJ-liposomes. Three days after transduction, transgene expression was determined by enzyme-link ed immunosorbent assay. Six weeks after placement of a constrictor on the left circumflex artery, 29 pigs were randomized to ischemic contro ls (n = 5), transmyocardial laser revascularization (n = 4), transmyoc ardial laser revascularization with expression plasmid beta-galactosid ase injections (n = 5), expression plasmid-vascular endothelial growth factor injections (n = 4), or transmyocardial laser revascularization with expression plasmid-vascular endothelial growth factor (n = 5) an d harvested 6 weeks after therapy. Six transmyocardial laser revascula rization pigs had either expression plasmid beta-galactosidase or expr ession plasmid-vascular endothelial growth factor injections and were harvested at 2 weeks. Normal pigs (n = 5) were included for comparison . Left ventricular free wall motion was assessed by a cardiologist in a blinded manner. Results: Transgene expression did not vary significa ntly with or without HVJ-liposomes in transfected transmyocardial lase r revascularization myocardium, However, expression was detected in 56 of 60 (93%) transmyocardial laser revascularization-transfected sites , but in only 10 of 20 (50%) non-transmyocardial laser revascularizati on sites (P < .001), All (5 of 5 hearts) of the transmyocardial laser revascularization-vascular endothelial growth factor treated hearts di splayed no evidence of wall motion abnormalities. Only these hearts ha d a statistically significantly different rate of wall motion abnormal ity compared with ischemic controls (P = .004). Conclusion: Transfecti on efficiency was improved with the use of transmyocardial laser revas cularization. Wall motion abnormalities were completely reversed withi n 6 weeks after transmyocardial laser revascularization with the direc t injection of an expression plasmid encoding vascular endothelial gro wth factor.