Hideto Emoto

Effects of stent design and serum cholesterol level on the restenosis rate in atherosclerotic rabbits

We investigated the effect of serum cholesterol level and stent design on the restenosis rate within the stent after balloon angioplasty and stent implantation using atherosclerotic rabbits. Two types of nickel/titanium stents with gaps (open stent) and without gaps (closed stent) between the wire coils were implanted into the aorta of the rabbits 10 weeks after atherosclerosis had been induced using a standard high cholesterol diet and balloon abrasion. Each rabbit had an open stent and a closed stent implanted into the infrarenal abdominal aorta. Between these two stents a control segment of the aorta was treated with angioplasty alone. The animals were divided into two groups according to the diet protocol as follows: in group I (n = 9) a high cholesterol diet was stopped after stent implantation; in group II (n = 10) a high cholesterol diet was maintained after stent implantation. Digital subtraction angiograms were obtained every 4 weeks for up to 24 weeks and the narrowest diameter of the arterial segments within each stent and in the segment between stents was measured. The diameter narrowing within the closed stent was greater in the high cholesterol group compared with the low cholesterol group: 12 weeks (2.57 +/- 0.09 mm in group I vs 2.14 +/- 0.15 mm in group II, mean +/- S.E., p < 0.05); 16 weeks (2.55 +/- 0.09 mm vs 2.14 +/- 0.12 mm, p < 0.05); 20 weeks (2.59 +/- 0.06 mm vs 1.98 +/- 0.12 mm, p < 0.01); and 24 weeks (2.45 +/- 0.11 mm vs 2.01 +/- 0.11 mm, p < 0.05). No significant differences in the narrowest diameter of the arterial segments were observed between high and low cholesterol groups in the angioplasty alone areas or within the open stents. There was a significant difference in the narrowest diameter between stents with versus those without gaps (at 12, 16, and 20 weeks poststenting in group I and at 4, 8, 12, 16, 20, and 24 weeks in group II). Thus the stent with the least metal is correlated with less stenosis and intimal hyperplasia. From these data we conclude that both stent design and serum cholesterol are important factors for restenosis after stent implantation.

Vascular stenting in normal and atherosclerotic rabbits. Studies of the intravascular endoprosthesis of titanium-nickel-alloy.

Percutaneous transluminal balloon angioplasty would be more effective if the rate of recurrent stenosis were reduced. To evaluate the prevention of restenosis after percutaneous transluminal angioplasty, intravascular endoprosthetic stents of titanium-nickel-alloy were implanted transluminally in seven normal and 21 atherosclerotic rabbits. In normal rabbits, a 3.5-mm diameter stent was implanted in the aorta and a 2.5-mm diameter stent in the right iliac artery, which were followed with serial angiograms from 6 weeks (n = 7) to 8 months (n = 4). There was a mean stenosis of 13.1% in the 2.5-mm and 13.6% in the 3.5-mm stent. There was no significant narrowing compared with the adjacent control segments of artery; histopathology showed a thin, fibrous neointima with smooth muscle cells. Each atherosclerotic rabbit was balloon dilated at two separate stenotic sites; each site was 2.0 cm in length. The aortic site (with 28.8 +/- 13.8% mean stenosis [+/- SD]) was dilated with a 3.5-mm balloon, and the iliac site (with 36.5 +/- 14.2% stenosis) was dilated with a 2.5-mm balloon. In each site, an intravascular stent of corresponding diameter and 7-mm length was implanted in one half of the dilated segment, assigned randomly, and the other half served as the angioplasty control. Angiographically observed restenosis rates and the corresponding histopathology were similar in the atherosclerotic segments that had angioplasty alone versus the atherosclerotic segments that had angioplasty plus stenting. The mean neointimal thickness in the aortas and iliac arteries, respectively, measured 247 +/- 181 microns (+/- SD) and 218 +/- 77 microns after 6 weeks (n = 8) versus 321 +/- 168 and 308 +/- 189 microns after 20 weeks (n = 5, p = NS). At 20 weeks follow-up, there was 29.1 +/- 29.8% (median, 16.4%) stenosis in the aortic stent versus 38.9 +/- 24.1% (median, 34.0%) stenosis in the percutaneous transluminal angioplasty control segment of aorta (n = 5, p = NS) and 81.4 +/- 25.5% stenosis in the iliac artery stent versus 89.3 +/- 15.3% stenosis in the PTA control segment of the right iliac artery (n = 5, p = NS). Comparing stenotic arterial segments treated with angioplasty alone with angioplasty plus intravascular stenting in the atherosclerotic rabbits showed that there was no significant difference in either the histopathologic changes or the restenosis rates.

Compliance effect on patency of small diameter vascular grafts

The compliance mismatch hypothesis as a cause of failure of small diameter grafts was investigated using 4 mm internal diameter, 5 cm long Biolized polyurethane grafts. The luminal surface of 0.5 mm thick Biomer sponge grafts was covered with 100 microns of crosslinked gelatin. Compliance matched, and noncompliant grafts had in vivo compliance values of 13.5 +/- 2.89 and 1.0 +/- 0.7 X 10(-2%) per mmHg, respectively. In vivo compliance defined as 2 X dD/dP X 1/Do was measured in situ using the ultrasonic Hokanson probe. Compliance values of compliant grafts equaled that of the canine carotid artery at 100 mmHg mean arterial pressure. Grafts were implanted using an end-to-end anastomosis in 14 dogs for 6 wk. Patency rates for compliant vs. noncompliant grafts were 64% (9/14) and 50% (7/14). Compliance values for compliant grafts decreased to a mean of 7.14 X 10(-2%) per mmHg. Anastomotic intimal hyperplasia at the proximal and distal ends of compliant and noncompliant grafts measured 239.9 +/- 128, 197 +/- 129 microns, 338.9 +/- 273.6, and 304.3 +/- 179.3 microns, respectively. There were no significant differences in localized anastomotic intimal hyperplasia at either graft end for either graft type. This study did not show any positive effects of graft compliance.

Intravascular endoprostheses. Effect of surface geometry on restenosis and side branch patency.

To investigate the effects of gaps between the wire pitches of a shape memory Nitinol alloy intravascular endoprosthesis (IVEP), 42 stents with and without gaps were implanted transluminally into the infrarenal abdominal aortae of 11 normal and 10 atherosclerotic rabbits. Digital subtraction angiography was done every 4 weeks to examine the restenosis rate and major side branch patency. Restenosis rates within IVEPs with gaps were significantly lower than in stents without gaps in both normal and atherosclerotic rabbits. The side branch patency rate was significantly higher with IVEPs having gaps. These results suggest that the placement of gaps between wire pitches reduced the restenosis rate within IVEPs, and prevented the obstruction of major side branches.

In Vitro Analysis of Plasma Protein Diffusion in Crosslinked Gelatin Coatings Used for Blood Pumps

Glutaraldehyde crosslinked gelatin surfaces, used as blood pump coatings in calves, have shown excellent long term blood compatibility. The study evaluated the diffusion and kinetics of plasma proteins into gelatin gel matrices using SDS-PAGE and GPC (gel permeation chromatography). The effects of plasma protein diffusion within the gel and the reactivity of bovine platelets to this surface were evaluated in vitro. Five percent crosslinked gelatin gels, 30–50 μm thick, were incubated with fresh bovine plasma for intervals of 5 minutes to 24 hours. Platelet reactivity to the gel surface was examined by exposing the gel surfaces to platelet rich plasma for 2 hours. Changes in platelet morphology were observed by SEM.

Study of heat dissipation to the lung from a thermal ventricular assist system.

The thermally powered left ventricular assist system (LVAS) requires that heat be dissipated to surrounding lung tissue and blood. This acute study was conducted in three anesthetized calves (weighing 84.3 +/- 14.3 kg) to evaluate the mechanisms involved in the dissipation of heat to the lung tissue. The heaters were placed in contact with the left lung surface and skeletal muscle tissue. Compared to the muscle tissue, heat flux to the lung was approximately three times higher for the same surface temperatures. For a constant heat flux, lung interface temperature tended to vary inversely with the cardiac output and ventilatory flow. This preliminary study demonstrated that the level of heat generated by the thermal LVAS can be effectively dissipated to the lung, with the convection mechanisms of airflow and blood flow playing a major role.

Methods for volume assessment of an air filled compliance chamber.

The air-filled (120 ml) compliance chamber employs a Dacron covered Hexsyn-butyl bilaminar diaphragm to minimize gas diffusion. Finite permeability dictates the need for a means to detect the remaining air volume and a refill port for gas addition. X-ray studies were used to detect radiopaque chamber markers in cadavers. Tangential X-ray cinematography enabled detection of chamber volumes less than 100 ml and diaphragm center deflection predicted volume to within +/- 6 ml of the actual volume. An electrically driven left ventricular assist pump (90 cc) was used to evaluate motor current (MC) and intracompliance pressure (IP) as indicators of low compliance volume. Peak MC was a function of both hemodynamic output power and compliance volume. Thus, if the peak current for a given hemodynamic output is known, variances may be indicative of low compliance volumes. The cyclic minimum IP vs. volume was +1, -3, and -13 mmHg for compliance volumes of 120, 90, and 80 cc, respectively. Ejection velocity did not significantly affect IP. In conclusion, X-ray studies and MC are useful as noninvasive means of assessing the need for compliance refill. IP, though measured invasively, is the most sensitive volume-dependent parameter.