Dong-Soo Lee

Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model

OBJECTIVEnWe evaluated the potency of therapeutic angiogenesis using intramyocardial injection of naked DNA expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in a porcine myocardial infarction model.nnnMETHODSnFour weeks after left anterior descending coronary artery ligation, 14 pigs were allocated to pCK-Null (negative control, n=7) or pCK-HGF-X7 (n=7) treatment groups. Gated myocardial single photon emission computed tomography was performed 4 and 8 weeks following coronary ligation. The effect of pCK-HGF-X7 on capillary density in the gene-injected myocardium was examined by histological analysis using alkaline phosphatase staining.nnnRESULTSnSegmental myocardial perfusion of the underperfused area (< or =70%) from coronary ligation increased in the pCK-HGF-X7 group (p=0.051), without significant differences in changes over time between the two groups (p=0.54). Systolic wall thickening (p=0.001), left ventricular end-diastolic (p=0.045) and end-systolic volumes (p=0.009), and left ventricular ejection fraction (p=0.041) changed in both groups without significant differences in changes over time between the two groups. The increase in the left stoke volume was higher in the pCK-HGF-X7 group than in the pCK-Null group (p=0.008). Histological analysis showed that capillary density was significantly higher in the pCK-HGF-X7 group than the pCK-Null group (p<0.001).nnnCONCLUSIONnIntramyocardial injection of pCK-HGF-X7 induced significant angiogenesis at infarct-border zone, and increased the left ventricular stroke volume probably caused by reverse remodeling process.

Improved Myocardial Perfusion and Thickening After Off-Pump Revascularization: 5-Year Follow-Up

BACKGROUNDnLate improvements in myocardial perfusion and thickening after off-pump revascularization were evaluated during a 5-year follow-up by myocardial single photon emission computed tomography.nnnMETHODSnBetween 2001 and 2003, 68 patients who underwent off-pump coronary artery bypass grafting using bilateral internal thoracic artery Y-composite (group Y, n = 41) or in situ (group I, n = 27) grafts for revascularization of the left coronary artery territory were enrolled. Myocardial single photon emission computed tomography was performed preoperatively and at 3 months, 1 year, and 5 years postoperatively. A 20-segment model was adopted. As an indicator of ischemic myocardium, the reversibility score was defined as a measure of rest minus stress perfusion values. A total of 374 segments that showed a reversibility score of > or = 7 preoperatively were included. Z values for thickening were calculated as observed values minus reference values divided by the reference standard deviation. Mixed-model analysis was used to compare the two groups with respect to the time sequences of myocardial reversibility scores and Z values.nnnRESULTSnPostoperative reversibility scores improved significantly at 3 months (p < 0.001) and further at 5 years (p = 0.030). Postoperative Z values improved significantly at 3 months (p < 0.001), between 1 year and 5 years (p = 0.006), and further at 5 years (p = 0.004). In the mixed models, there were no significant differences in reversibility scores and Z values between groups Y and I at any point.nnnCONCLUSIONSnReversibility scores and thickening gradually improved during 5 years after off-pump revascularization using bilateral internal thoracic arteries. No significant differences were observed between Y-composite and bilateral in situ grafts in terms of reversibility score and thickening improvement at 5 years postoperatively.