Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia.

Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4+/-15.4 capillaries per 100 myocytes in GI, 84.6+/-14.7 in GII (P<0.01 vs GI and GIII) and 49.3+/-13.6 in GIII, and arteriolar density was 1.9+/-0.6 arterioles per mm2 in GI, 3.0+/-0.9 in GII (P<0.01 vs GI and GIII) and 1.5+/-0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.

Densitometric quantitative analysis of intracoronary ultrasound images: anatomopathological correlation.

To establish if the videodensitometric analysis (VDA) of the intracoronary ultrasound images (IVUS) can predict the qualitative and quantitative composition of the atherosclerotic coronary plaques, thirty-one patients who had undergone anatomopathological study of directional coronary atherectomy (DCA) samples and pre- and post-intervention IVUS image were analyzed. The video IVUS images were digitized in a 512 x 512 matrix and analyzed for densitometric differences with an Automatic Image Analysis System (AIAS) (Vidas 2000, Zeiss Kontron). The components of the plaque were arbitrarily divided into three densitometric categories using a 256 gray scale: high density (HD) 121-255, medium (MD) 81-120 and low (LD) 30-80. The relative percentage of each component was automatically recorded. The DCA samples were microscopically examined and put into the AIAS. The components were divided into: collagenous tissue (CT); lipid-necrotic debris (LND); proliferative tissue (PT). The area of each component was expressed as a percentage of the total. Linear correlation analysis was applied. Comparison between the IVUS and the histological composition of the plaque showed that: HD corresponded to CT; MD to PT; LD to LND. The correlation between the percentage distribution of the densitometric categories and the anatomopathological components showed a correlation coefficient r = 0.91 between HD and CT; r = 0.87 between MD and PT; r = 0.88 between LD and LND. The VDA of the IVUS can distinguish three basic components of the atherosclerotic plaque: fibrous, lipid-necrotic and proliferative tissue, allowing absolute and relative quantitative analysis. This capability may be of interest for device selection and histopathological correlation.

ST-segment computerized monitoring before and after angioplasty: clinical correlation with recurrent angina during the short-term follow-up.

The purpose of this study was to determine whether computerized ST-segment monitoring previous to percutaneous transluminal coronary angioplasty (PTCA) and after performance of this procedure may be useful to discern a pattern of recurrent angina. For this purpose, we analyzed 57 patients (11 women and 46 men, mean age 60 years) before and after treatment with balloon procedure. These patients were followed up during the next 3 months. A computerized electrocardiographic (ECG) device was used which was capable of recording simultaneously all 12 leads at rest. It was programmed to store a complete ECG every 5 min and was capable of detecting any abnormal ST alteration > than 0.5 mV at 80 ms after J junction, including R-wave amplitude. Measurements were started before (mean time 7.26 h) and after (mean time 7.96 h) the procedure. The value for ST amplitude at the J junction was used as the 0 point; then the most negative depression or the most positive elevation value was considered as the most abnormal ST alteration during monitoring. The patients were followed up for 3 months for the purpose of recognizing recurrent angina or establishing the occurrence of death. Twelve patients (30%) had recurrent angina. Discriminant function analysis revealed that ST monitoring in these patients showed significant difference after PTCA in comparison with controls, both in the frontal plane [ST depression 170 +/- 52 mV vs. 231 +/- 23 (p = 0.02)] and in precordial leads [176 +/- 16 vs. 80 +/- 6.19 mV (p = 0.0001)].(ABSTRACT TRUNCATED AT 250 WORDS)