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This study examined the efficiency of adenoviral-mediated gene transfer in experimental vein grafts and cultured human saphenous vein under physiologic conditions using clinically relevant exposure times, pressures, and viral concentrations. The external jugular veins of 25 male New Zealand White rabbits were exposed to 0.5 mL of replication-deficient adenovirus vectors encoding beta-galactosidase (AdlacZ), control adenovirus (AdBg/II), or vehicle at pressures ranging from 0 to 120 mmHg for 10 min. Veins were excised and grafted into the carotid circulation. After 5 days, the vessels were reexposed, excised, and stained with X-gal chromagen for beta-galactosidase (beta-gal) activity. Gene transfer was also performed in 13 segments of human saphenous vein discarded at the time of bypass grafting. The veins were cultured for 0-21 days and assayed for beta-gal activity as above. Rabbit vein grafts exposed to high-pressure AdlacZ transfection showed significant transgene expression in 100% of grafts (39 +/- 2% positive cells/hpf) while only 60% of those transfected at low pressure expressed beta-gal (9 +/- 3% positive cells/hpf). All human veins exposed to AdlacZ expressed beta-gal to a variable degree (range 10-50% positive cells/hpf). No control grafts or veins expressed the transgene. Efficient adenoviral-mediated gene transfer in experimental vein grafts and human saphenous vein segments can be achieved using clinically feasible parameters of exposure time, pressure, and viral concentration.

Atherosclerosis is a degenerative process characterized by endothelial cell dysfunction, inflammatory cell adhesion and infiltration, and the accumulation of cellular and matrix elements leading to the formation of fibrocellular plaques. In the end stages, advanced occlusive plaques limit blood flow and oxygen delivery resulting in the well-known ischemic syndromes of the coronary, skeletal muscle, mesenteric, and cerebrovascular circulation. Moreover, sudden critical ischemic events may be precipitated by plaque disturbance, rupture, hemorrhage, and/or thrombosis. Traditional pharmacologic approaches have been effective in reducing serum cholesterol and controlling thrombosis but, in the main, have had little impact on the treatment of advanced lesions. The purpose of this review is to examine the current status of gene therapy for vascular proliferation, aberrant endothelial function, thrombosis, peripheral ischemia, and modification of the blood/biomaterial interface.

The purpose of this investigation was to measure vascular input impedance in infrainguinal vein grafts and assess the importance of clinical and hemodynamic parameters in predicting graft patency. Fifty-seven patients undergoing infrainguinal vein bypass grafting for limb salvage (n = 40) or claudication (n = 17) were prospectively studied. At the time of revascularization, simultaneously acquired intraluminal pressure and blood flow waveforms were digitized at 200 Hz and subjected to Fourier transformation in near real-time. Input impedance was calculated at baseline (immediately after unclamping) and after stimulation with either papaverine or completion arteriography. Resistance (Rin) was calculated as mean pressure divided by mean blood flow (Q). Characteristic impedance (Z0) was calculated as the mean of harmonics 3-10. Intraoperative data acquisition required approximately 5 min, utilized the completion angiography cannula already in place, and was uncomplicated in all patients. Stimulation with either papaverine or arteriography resulted in increased Q (72 +/- 7 to 146 +/- 11 ml/min, p < 0.001), decreased Rin (126 +/- 13 to 52 +/- 4 x 10(3) dyne.s.cm-5, p < 0.001), and slightly decreased Z0 (18 +/- 2 to 15 +/- 1, p = 0.002). After a mean follow-up of 20 months, the 2-year primary patency, secondary patency, limb salvage, and survival rates were 61 +/- 8%, 74 +/- 7%, 76 +/- 6%, and 86 +/- 6%, respectively. Primary patency was not associated with any of the clinical variables studied including age, sex, smoking history, history of previous vascular surgery, hypertension, coronary artery disease, diabetes mellitus, creatinine, indication for revascularization (claudication versus limb salvage), anesthesia (general versus regional), or level of distal anastomosis (popliteal versus infrapopliteal). Furthermore, there was no association between primary patency and baseline Q, baseline Rin, or stimulated Z0. However, using univariate analysis, patency was positively associated with decreased stimulated Rin (p = 0.002), elevated stimulated Q (p = 0.006), and decreased baseline Z0 (p = 0.02). Multiple regression analysis identified stimulated Rin as the only independent predictor of primary patency (p = 0.002). Stimulated Rin > or = 50 x 10(3) dyne.s.cm-5 was 71% sensitive and 65% specific for graft failure. It is concluded that 1) vascular input impedance can be simply and reliably measured in the operating room, and 2) elevated stimulated Rin is an independent predictor of primary patency.