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The purpose of this study was to determine if the luminal surface of balloon-dilated arteries can be re-endothelialized circumferentially with use of normal endothelial cells (ECs) and superparamagnetic microsphere-containing endothelial cells (MagECs) to cover gravity-dependent and independent arterial surfaces, respectively.MagECs were obtained after phagocytosis of albumin-coated superparamagnetic polystyrene microspheres by rabbit microvascular ECs. The effect of microsphere internalization on cell adhesion was determined in vitro by comparing ECs and MagECs in terms of time courses of adhesion to fibronectin and cell retention after exposure to a shear stress. In vivo re-endothelialization was performed by delivering fluorescently labeled ECs and MagECs to a balloon-dilated artery with a double-balloon catheter, placing a magnet over the artery, and rotating the rabbit axially. Endoluminal coverage of arterial cross-sections was estimated by epifluorescence microscopy.Under the influence of gravity, in vitro cell adhesion to fibronectin after 5, 10, and 15 minutes was similar for the ECs (34%, 74%, and 70%) and MagECs (40%, 56%, and 93%). In vitro cell retention after exposure to a shear stress (25 dynes/cm2) was greater (P.05) for ECs than for MagECs (82% vs 69%). Use of ECs plus MagECs in vivo resulted in cell delivery that was nearly circumferential.Delivery of a mixture of ECs and MagECs in combination with animal rotation and a magnetic field provide nearly circumferential delivery of ECs to the luminal surface of balloon-dilated arteries. The presence of superparamagnetic microspheres in cells does not impede cell adhesion but does decrease cell retention after exposure to a fluid shear.

The placement of endothelial cells on the surfaces of arteries immediately after vascular interventions has the potential to limit restenosis by inhibiting intimal thickening and by stimulating arterial enlargement. Because such re-endothelialization is dependent on rapid formation of strong endothelial cell-matrix interactions, experiments were performed to identify the extracellular matrix that provided endothelial cells with the greatest resistance to detachment by a shear stress in the least amount of time.Rabbit microvascular endothelial cells were plated onto glass slides coated with collagen, laminin, vitronectin, or fibronectin. After allowing 5-45 minutes for cell adhesion, each slide was placed in a parallel plate chamber, and the number of cells present before and after exposure of the cells to shear stresses (1-25 dynes/cm2) were counted.Endothelial cell retention to the matrix-coated slides was time and matrix dependent. The percentages of endothelial cells retained after adhesion times of 5, 15, 30, and 45 minutes followed by exposure to 15 dynes/cm2 were 9%, 20%, 32%*, and 38%* for collagen; 7%, 20%, 36%*, and 49%* for laminin; 35%, 47%, 62%, and 76%* for vitronectin; and 64%, 58%, 71%, and 78% for fibronectin, respectively (*P.05 versus 5 minutes adhesion). Similar results were obtained for lower and higher shear stresses, indicating that cell retention was independent of shear stress above 1 dyne/cm2.The resistance of freshly adherent endothelial cells to detachment by shear stress is matrix- (fibronectin approximately equal to vitronectinlaminin approximately equal to COL) and time-dependent. Fibronectin provided the greatest cell retention in the least amount of time.

Purpose Pseudoaneurysms represent contained disruption of the arterial wall. Iatrogenic pseudoaneurysms frequently complicate complex endovascular procedures. With use of an animal model, the authors attempted to determine the safety and efficacy of using a perfusion balloon catheter (PBC) to thrombose surgically created pseudoaneurysms. Materials and Methods An in vitro system measured maximum flow volume through a 5-F PBC. Pseudoaneurysms were created in domestic swine with use of a jugular vein patch anastomosed to a femoral arteriotomy. The PBC was inflated across the pseudoaneurysm neck for 30-minute intervals until thrombosis was confirmed by ultrasound. Completion arteriography was performed to evaluate for vascular complications. Results Maximum flow through the PBC was 62.6 mL/min measured at a constant pressure gradient of 120 mm Hg. Five pseudoaneurysms were created in four animals. The PBC completely thrombosed all five lesions. The mean treatment duration was 129 minutes (± 39 minutes SD). No native arterial injury, in situ thrombus, or distal embolization occurred. Partial recanalization of three of the five treated pseudoaneurysms was identified on follow-up arteriography and gross sectioning ( n = 2 and n = 1, respectively). Conclusion The PBC safely and effectively thrombosed surgically created pseudoaneurysms. Partial recanalization of treated pseudoaneurysms was demonstrated. Clinical trials are warranted.

Purpose Experiments were performed to determine if the percutaneous placement of endothelial cells on denuded arterial surfaces is feasible. Materials and Methods For in vitro adhesion assays, rabbit microvascular endothelial cells were stained with a fluorescent marker and placed on the luminal surface of disks of denuded rabbit aorta. At varying times thereafter, the nonadherent cells were removed, and the adherent cells were quantitated with use of fluorescence microscopy. For in vivo studies, angioplasty was performed on external iliac arteries in five rabbits, and a double-balloon catheter, positioned at the dilatation site, was used to deliver fluorescent rabbit microvascular endothelial cells. Ten minutes ( n = 2), 1 hour ( n = 2), 1 day ( n = 1), or 3 days ( n = 1) after cell placement, the number of fluorescent cells remaining on each artery was determined. Results In vitro rabbit microvascular endothelial cell attachment was ( a ) serum-dependent, peaking with media containing 25% autologous serum; ( b ) time-dependent, peaking at 30 minutes; and ( c ) cell density-dependent. In vivo rabbit microvascular endothelial cell attachment was ( a ) noncircumferential, ( b ) appeared to be gravity-dependent, and ( c ) appeared unchanged over 3 days with respect to number of cells per cross-section and length of artery having endothelium. Conclusions Percutaneous delivery of endothelial cells onto denuded arterial surfaces with use of optimal conditions is feasible and these cells remain adherent for at least 3 days.

Purpose To determine the feasibility of using hydrogel-coated angioplasty balloons to deliver drugs that inhibit vascular smooth muscle cell (VSMC) proliferation. Materials and Methods In initial experiments, the tyrphostin RG-50872 (1 μmol/L) completely inhibited VSMC proliferation induced by platelet-derived growth factor (PDGF) in vitro when RG-50872 treatment preceeded PDGF exposure by 15 minutes. This inhibition was reversible and was not due to cell toxicity. In further experiments, hydrogel-coated and silicone-coated angioplasty balloons (2.5 mm in diameter by 20 mm in length) were coated with either 10 μL of RG-50872 (40 mmol/L in dimethyl sulfoxide [DMSO]) or DMSO vehicle, or were left uncoated. Afterward, each angioplasty balloon was inflated, submerged in 50 mL of culture media, and agitated for 2 minutes to promote drug release. Dilutions of this media were tested for their ability to inhibit VSMC proliferation. Results All hydrogel-coated balloons ( n = 5) released sufficient RG-50872 to inhibit PDGF-induced VSMC proliferation by 95% or more, whereas none of the silicone-coated balloons ( n = 4) did. DMSO-treated and untreated balloons had no effect on proliferation. Conclusion These findings demonstrate that the hydrogel-coating on angioplasty balloons can take up and release sufficient RG-50872 to significantly inhibit smooth muscle cell proliferation. Further in vivo experiments are needed to determine if hydrogel-coated balloons can deliver sufficient RG-50872 to the arterial wall to affect VSMC proliferation.

The purpose of this study was to determine if exposure of arteries to thrombin increases arterial sensitivity to serotonin and could thereby promote vasospasm. Rings of rabbit abdominal aorta, with endothelium intact or removed, were pretreated with vehicle or thrombin (2.5 U/mL). Thereafter, arterial contractions in response to cumulative additions of serotonin were recorded. Arterial contractions were expressed as a percentage of maximal potassium chloride-induced contractions. Arterial sensitivity was expressed as the EC50, the concentration of serotonin that produced a half-maximal contraction. Exposure of aortic rings to thrombin alone produced contractions of 11% and 22% for rings with and without endothelium, respectively. Removal of the endothelium had no effect on maximal serotonin-induced contractions (93% with endothelium vs 98% without). In contrast, maximal serotonin-induced contractile force was increased after pretreatment with thrombin (107% vs 121% for rings with and without endothelium, respectively; P less than .01). Arterial sensitivity to serotonin was not affected by the removal of endothelium. However, thrombin pretreatment increased (P less than .01) arterial sensitivity to serotonin 2.6-fold and 4.7-fold for rings with and without endothelium, respectively. The results of this study demonstrate that arterial contractions due to serotonin are amplified by thrombin and suggest that vasospasm may be more likely to occur at sites in arteries where the endothelium is absent and both thrombin and serotonin are present.

The effects of balloon angioplasty (BA) and laser-assisted balloon angioplasty (LABA) on arteries were compared. Atherosclerosis was induced in the iliac arteries of New Zealand White rabbits by means of balloon denudation and a diet supplemented with 1% cholesterol and 3% peanut oil. Six weeks later, one iliac artery was dilated with a 2.5- or 3.0-mm-diameter balloon. The contralateral iliac artery was treated with a 1.5-mm-diameter laser probe heated with 6 W of argon laser energy, and then BA was performed. Four weeks later, the mean luminal diameter of the LABA-treated arteries was smaller than that of the BA-treated arteries (BA, 1.57 mm +/- 0.15; LABA, 0.82 mm +/- 0.19; P less than .01). This restenosis was due to greater intimal fibrocellular proliferation (intimal area: BA, 0.83 mm2 +/- 0.16; LABA, 1.41 mm2 +/- 0.26; P less than .05). The LABA-treated arteries produced less potassium chloride-induced maximal force (P less than .01) and had smaller incremental elastic moduli (P less than .05) than did the BA-treated arteries. LABA is not the treatment of choice for small-caliber arteries, in which thermal injury to the arterial wall would be significant.