Primary stenting in femoropopliteal occlusive disease - what is the appropriate role?

Endovascular treatment of femoropopliteal occlusive disease is challenging and often limited by its unique anatomic, hemodynamic and biomechanical constraints. Despite technical improvement, percutaneous transluminal angioplasty alone is not adequate to provide satisfactory long-term patency. Several randomized controlled trials have shown that primary nitinol stenting can provide a better short-term radiological patency in intermediate lesion, but the results were often limited by intrinsic stent complications, particularly in-stent restenosis. Solutions to long lesions have been more elusive. To date, many novel technologies have been developed with a goal of improving stent design for this specific environment. Interwoven stents are made to provide a higher radial strength and kink resistance. Covered stents are designed to prevent the ingrowth of intimal hyperplasia, which is the main cause of restenosis in bare metal stent. Drug-eluting stents have shown improved patency in clinical trials. Bioabsorbable stents, combining biological agents and mechanical scaffold, provide temporary vascular support while reducing implant-related vascular inflammation in the long term. New developments in balloon angioplasty, such as drug elution, provide a challenge to stenting in this arena. Although these technologies look promising, a uniform reporting system and large-scale comparative studies with longer follow-up are needed to evaluate their clinical effectiveness in the future.

A morphologic study of chronic type B aortic dissections and aneurysms after thoracic endovascular stent grafting.

BACKGROUND: The long-term results of treating chronic aortic dissections and aneurysms in association with dissections with thoracic endovascular aortic repair (TEVAR) are unknown, and the timing for intervention is uncertain. We evaluated the morphology of stent graft and aorta remodeling and the volumetric changes in these patients after successful TEVAR. METHODS: Serial computed tomography scans of 32 patients who underwent TEVAR for uncomplicated chronic dissections (group A, n = 17) and chronic dissections with aneurysms (group B, n = 15) were analyzed at 1, 6, 12, and 36 months. Stent graft diameter changes and positional migration were assessed three-dimensionally using Mimics 14.0 (Materialize, Leuven, Belgium). Volumetric data for true lumen, false lumen, thrombus load, and aortic size were measured by Aquarius iNtuition 4.4 software (TeraRecon, San Mateo, Calif). Results were compared between the two groups and with stent graft diameter, length, and oversizing. RESULTS: Aortic stent grafts remodeled progressively, with inlet area increasing 4.4%, 10.1%, and 14.2% and outlet area increasing 42.6%, 67.2%, and 72.3%, respectively, at 6, 12, and 36 months. True lumen volume increased progressively in group A (114 to 174 mL) and group B (124 to 190 mL) from baseline to 36 months. False lumen volume decreased in group A (150 to 88 mL) and group B (351 to 250 mL), whereas thrombus load in the false lumen increased from 73% to 80% in group A and 84% to 87% in group B in 3 years. Eight patients (4 in each group) showed an increase in total aortic volume of >10%, 12 showed a static volume, and 12 showed shrinkage. Aortic volume change had no relationship to pathology, stent graft sizing, and thrombus load but was positively associated with the placement of a longer graft. A small but progressive distal migration of stent grafts was noted in all patients (3.1, 4.5, and 5.1 mm at 6, 12, and 36 months) but was more prominent in shorter stent grafts (≤ 162 mm). No deaths, rupture, or secondary interventions occurred during follow-up. CONCLUSIONS: Aortic remodeling after TEVAR in chronic dissection is a continuous process. There were no significant differences between chronic dissections and aneurysms in all volumetric parameters. Treating chronic dissections early, before aneurysm formation, did not appear to have a morphologic advantage.

The effects of freezing versus supercooling on vascular cells: implications for balloon cryoplasty.

PURPOSE: To investigate the effects of supercooling, a phase whereby cells are below 0 degrees C but still in a liquid state, and freezing, the phase when cells become solid, of vascular cells in culture. MATERIALS AND METHODS: Bovine aortic endothelial cells and smooth muscle cells were supercooled to -10 degrees C with or without freezing for 3, 30, or 60 seconds and then rewarmed to 37 degrees C for 24 hours. Viability was assessed by means of trypan blue exclusion, and apoptosis was assessed with the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay. RESULTS: Viability of smooth muscle cells decreased 49% after freezing versus supercooling (P< .05). Endothelial cells maintained greater viability rates. A 19.5% smooth muscle cell apoptotic rate was observed after freezing, whereas smooth muscle cell supercooling yielded rates of only 11% (P< .05). A 4.17% endothelial cell apoptotic rate was observed after freezing, whereas supercooled endothelial cells yielded a 1.76% rate (P< .05). CONCLUSIONS: Freezing results in decreased viability and increased apoptosis compared to supercooling in both cell lines. Smooth muscle cells appear more susceptible to freezing. The biologic effects of freezing on vascular cells may elucidate the mechanisms behind the enhanced patency after cryoplasty of atherosclerotic lesions.

Synergistic effect of cool/thaw cycles on vascular cells in an in vitro model of cryoplasty.

PURPOSE: Cryoplasty combines mechanical dilation with supercooling of the vessel and has shown encouraging preliminary results in the management of atherosclerotic lesions. However, the mechanisms of action and the optimum inflation regimen are still not well established. This study investigates the effects of single and dual supercooling and rewarming cycles on the survival responses of smooth muscle cells (SMCs) and endothelial cells (ECs). MATERIALS AND METHODS: Bovine aortic SMCs and ECs were cultured separately in six-well plates with medium supplemented with 10% fetal bovine serum. In the one-cycle treatment group, the cells were supercooled for 60 seconds to -10 degrees C and then rewarmed rapidly in a water bath at 37 degrees C for another 60 seconds. Two-cycle treatment was done by supercooling and rewarming the cells twice. The samples were then put into an incubator at 37 degrees C for 0, 6, 12, and 24 hours. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure apoptosis and phospho-Akt immunohistochemistry and immunoblot analysis were employed to assess activation of Akt. RESULTS: A significant increase of apoptotic cells was observed in the two-cycle procedure versus the one-cycle procedure. In both groups, there were more apoptotic SMCs than ECs. Akt activation was higher in ECs by a factor of three compared with SMCs (P < .05). CONCLUSIONS: The higher apoptotic rate and the absence of Akt activation of SMCs versus controls in both treatment groups may imply the potential of a lower restenosis rate, especially after two cycles of supercooling and rewarming. Further in vivo and clinical investigations are needed to confirm results of the in vitro testing.

Direct comparison of endothelial cell and smooth muscle cell response to supercooling and rewarming.

BACKGROUND: Cryoplasty combines mechanical dilatation with the delivery of hypothermia to atherosclerotic plaques. The response of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to supercooling and subsequent rewarming is still not clear. This study investigated the differential effects of vascular cell survival and proliferation in an in vitro model simulating cryoplasty. METHODS: Bovine aortic ECs and SMCs were cultured separately with medium supplemented with 10% fetal bovine serum. The samples were supercooled to -10 degrees C for 0, 60, or 120 seconds on a cooling stage and then rewarmed in an incubator at 37 degrees C for 0, 6, 12, or 24 hours. Terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) and 5'-bromo-2'-deoxyuridine incorporation were used to measure the degree of apoptosis and proliferation respectively. Activation of protein kinase B (AKT), P70 S6 kinase, and P44/42 mitogen-activated protein kinase (MAPK) were assessed by Western blot and quantified using densitometry. Results are given as mean +/- standard error of mean and analyzed by analysis of variance. RESULTS: SMC and EC apoptosis were significantly increased with increasing supercooling and rewarming time, with a higher rate in SMCs. SMC apoptosis was maximal at 60 seconds cooling, followed by 24 hours rewarming (17.05% +/- 0.44%), whereas maximal EC apoptosis was after 120 seconds cooling, followed by 24 hours rewarming (4.21% +/- 0.22%, P < .05). Higher AKT activation was observed in ECs, with a maximum obtained of 3.34-fold at 120 seconds cooling with 24 hours rewarming (P < .05); only modest activation was found in SMCs. ECs had a decreased proliferation with cooling and rewarming time, and although SMCs maintained their low proliferative rate, ECs still had a higher overall proliferation rate that was statistically significant at 60 and 120 seconds cooling without rewarming compared with noncooling and nonrewarming (P < .05). Both p70S6 kinase and p44/42 MAPK activities decreased in SMCs, with significant drop at 60 seconds cooling, followed by 12 hours rewarming (P < .05). However, ECs showed a significant rise of P70 S6 kinase activity at 60 seconds cooling with 12 hours rewarming by 1.62-fold and P44/42 MAPK at 120 seconds cooling with 24 hours rewarming by 1.74-fold (P < .05). CONCLUSION: The higher apoptosis and lower proliferation of SMCs compared with ECs demonstrate the different effects of supercooling and rewarming on different vascular cell types. This information may be important in helping to understand the mechanism by which cryoplasty of atherosclerotic lesions may result in less restenosis.

Cryosurgery: A review.

Cryosurgery dates back to the 19th century, with the description of the benefits of local application of cooling for conditions such as pain control. Once commercial liquefied gases became available, more progress was made in the use of cryotherapy for localized lesions. As understanding of disease response to freezing increased, safer techniques for performing freezing procedures helped prepare its clinical application in different clinical situations, such as prostate disease and bronchial cancers. Cryosurgical techniques are less invasive and have lower morbidity compared with surgical resection. However, the use of cryosurgery has been limited by a lack of good understanding of the underlying mechanisms of tissue destruction. To apply cryosurgery clinically, and to extend its use, it is important to understand the mechanisms of freeze injury on cells, and to control the thermal parameters.

Vascular smooth muscle cell apoptosis induced by "supercooling" and rewarming.

PURPOSE: The underlying mechanisms for the reduction in restenosis caused by cryoplasty for peripheral atherosclerotic lesions are not well understood. Because vascular smooth muscle cells (SMCs) are known to play a critical role in restenosis and neointimal hyperplasia, the aim of this study was to determine SMC survival under conditions of "supercooling" and/or rewarming. MATERIALS AND METHODS: Bovine aortic SMCs were supercooled to -10 degrees C for 0, 60, or 120 seconds with a custom-designed conduction cooling stage and then rewarmed to 37 degrees C in an incubator for 0, 12, or 24 hours. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was used to measure the degree of apoptosis. Activation of Akt (ie, protein kinase B), a key signal protein involved in cell survival, was assessed by Western blot analysis. RESULTS: An increase in apoptotic SMCs was observed with increasing supercooling and rewarming time. Akt was significantly activated at only the most severe condition (120 seconds of supercooling and 24 hours of rewarming), which showed a 2.03-fold increase compared with the group without rewarming. CONCLUSIONS: The data suggest that SMC apoptosis occurs with supercooling and rewarming. Protective cell survival mechanisms were activated only late in the rewarming phase. This may partially explain the long-term patency observed with cryoplasty of atherosclerotic peripheral lesions.