Morphological and pharmacological characterization of the porcine popliteal artery: A novel model for study of lower limb arterial disease.

OBJECTIVE: This study was undertaken to characterize structural and pharmacological properties of the pig popliteal artery in order to develop a novel system for the examination of lower limb blood flow regulation in a variety of cardiovascular pathologies, such as diabetes-induced peripheral artery disease. METHODS: Popliteal arteries were isolated from streptozocin-induced diabetic pigs or age-matched saline-injected control pigs for morphological study using transmission electron microscopy and for examination of vasoreactivity to pharmacological agents using wire myography. RESULTS: Transmission electron microscopy of the porcine popliteal artery wall revealed the presence of endothelial cell-smooth muscle cell interactions (myoendothelial junctions) and smooth muscle cell-smooth muscle cell interactions, for which we have coined the term "myo-myo junctions." These myo-myo junctions were shown to feature plaques indicative of connexin expression. Further, the pig popliteal artery was highly responsive to a variety of vasoconstrictors including norepinephrine, phenylephrine, and U46619, and vasodilators including acetylcholine, adenosine 5'-[ß-thio] diphosphate, and bradykinin. Finally, 2 weeks after streptozocin-induced diabetes, the normalized vasoconstriction of the pig popliteal artery to norepinephrine was unaltered compared to control. CONCLUSIONS: The pig popliteal artery displays structural and pharmacological properties that might prove useful in future studies of diabetes-associated peripheral artery disease and other lower limb cardiovascular diseases.

Contemporary management of critical lower limb ischemia in TASC D lesions with subintimal angioplasty in femoro-popliteal lesions, tibial angioplasty and sequential compression biomechanical device for infra-inguinal arterial occlusion. Experience and quality of life outcome learned over 25 years.

AIM: Patients with end-stage critical limb ischemia (CLI) survive on borrowed time and amputation is inevitable if an aggressive management stratagem is not instigated. Our primary aim was to equate effectiveness of subintimal angioplasty (SIA) and tibial balloon angioplasty (TBA) in sustaining clinical improvement and amputation free survival (AFS) in patients with CLI TASD II D. Moreover, patients with severe CLI, who were not suitable for revascularization and who were offered therapy with a sequential compression biomechanical device (SCBD) were scrutinised as part of a comprehensive lower limb salvage program. METHODS: From 2002-2012, 5876 patients were referred with peripheral vascular disease (PVD); 987 presented with CLI and 798 had intervention; 189 patients presenting with CLI were not candidates for revascularisation, out of which 171 were offered SCBD. We formed a prospective observational group study of 441 patient who had TASC D disease. All of these patients presented as emergencies and were allocated to the next available treatment list. Duplex ultrasound arterial mapping (DUAM) was the sole preoperative investigation tool in 92% of all cases. Of the 441 patients studied, 190 patients (206 procedures) has SIA for TASC D femero-popliteal occlusions, 80 patients (89 procedures) had TBA and cool eximer laser angioplasty (CELA) for tibial artery occlusions and 171 patients with severe CLI were not suitable for revascularization and joined the SCBD program. Mean age (SIA 73±13 years vs. TBA/CELA 74±8 years vs. SCBD 75±13 years), and comorbidity severity scores (P>0.05) were similar between groups. RESULTS: Perioperative mortality within the SIA group was 1.6% vs. 0% within the TBA group and 0.6% in SCBD. Length of hospital stay within the TBA group was 3.8±2 days vs. SIA 14±16 days, P<0.0001. The 5-year freedom from major adverse events (MAE) for the SIA group was 68% that was comparable to the results obtained for both the TBA group; 59%, and SCBD group: 62.5% (P=0.1935). Five-year freedom from target lesion revascularization was 85.9% within the SIA group and 79% within the TBA group. A sustained clinical improvement was seen in 82.8% of primary SIA and 68% of TBA, which mimics the outcome of SCBD at 68% at one year. A total of 83% SCBD patients had no rest pain within one week of starting the program and gangrene remained dry and non-progressive. Ulceration healed in all but 12 patients. There were no device-related complications. Limb salvage was 94% at 5 years. All-cause survival was 69%. Quality time spent without symptoms of disease or toxicity of treatment (Q-TWiST) was 24.7 months for SIA and 8.5 months for TBA and was 38.13 for SCBD for a total of 708 months of usage. Cost per quality adjusted-life years (QALY) for SIA was € 5662.79, € 12,935.18 for TBA and € 2943.56 for SCBD. CONCLUSION: All treatment pathways augmented patient-specific Q-TWiST with substantial cost reduction. SIA, TBA and SCBD expand AFS and symptom-free survival. All treatment modalities are minimally invasive and allow for a high patient turnover without compromising limb salvage, once they are performed by experienced vascular surgeons in high deliberate practice volume centers.

Color-flow duplex scanning of the leg arteries by use of a new echo-enhancing agent.

OBJECTIVE: This was a dose-finding and effectiveness study of a newly developed contrast-enhancing agent, sulphur hexafluoride (SF(6)), in patients with peripheral arterial disease in whom the therapeutic policy could not be established on the basis of standard color-flow duplex scanning of the leg arteries. METHODS: In this open-label, randomized, dose-ranging, crossover design, 14 patients in whom the assessment of vessel patency was difficult because of poor visibility (low-flow state) or extensive wall calcifications were studied. Contrast-enhanced duplex scanning was performed on the upper leg (n = 4), lower leg (n = 6), or pedal (n = 4) arteries after intravenous injection of four different dosages of SF(6). The results were compared with those from selective angiography of the vessel of interest. Contrast duration and agreement about the diagnosis and the confidence in the diagnosis were obtained before and after administration of the contrast agent. RESULTS: No adverse effects of the contrast agent were seen. Overall agreement was reasonable with regard to vessel patency between contrast-enhanced duplex scanning and angiography (71%). Nine of 14 vessels (64%) appeared open when contrast was applied. In four cases this could not be confirmed by angiography; in two of these cases this was due to the presence of collateral vessels. All vessels that appeared occluded with the contrast agent were also occluded on the angiogram. The confidence in the diagnosis increased from 56% to 91% after contrast administration (P <.0001). CONCLUSION: SF(6)-enhanced color-flow duplex scanning is a safe method that may improve the assessment of the patency of leg arteries, particularly in low-flow states. The visualization of collateral vessles during (enhanced) duplex scanning may be misleading because they may be regarded as the vessel of interest.

Clinical and morphological aspects of Buerger's disease.

BACKGROUND: Thirty-five patients with TAO and 35 with ASO have been studied. To determine differences between these two arterial diseases, we used clinical criteria, arteriographic and morphological methods. The peripheral (below the bifurcation of the popliteal artery) angiographic changes were found in TAO with 94% sensitivity, 94% specificity and with 96% of positive predictive value. Other clinical diagnostic criteria for differential diagnosis had a lower value (they had high sensitivity and low specificity or low sensitivity and high specificity). RESULTS: The histologic studies confirmed the clinical diagnoses of Buerger's disease in 92,9% cases. The pathologic findings in TAO and ASO were different. CONCLUSIONS: Our investigations proved that the characteristics of Buerger's disease include the development of changes not only in small and medium size arteries or veins, but also in microcirculation.

Histologic and morphologic effects of rotary atherectomy on human cadaver arteries.

Intimal splitting and medial dissection caused by balloon angioplasty and thermal burns and subintimal vacuolization caused by laser angioplasty have been proposed as potential causes of failure from these respective procedures. The purpose of this study was to evaluate the histologic and morphologic effects of a new high speed rotary atherectomy device (the Rotoblator) on human cadaver arteries. Fifteen stenotic human cadaver superficial femoral and popliteal arteries were harvested and atherectomized using the Rotoblator. Histologically, on cross-section, the atherectomized arteries exhibited a denuded endothelial layer, a smooth rounded luminal contour, minute plaque separation from the media, absence of plaque fragmentation, and variable remaining rim of atheromatous plaque. The media showed variable loss of the internal elastic lamina, normal remaining elastin, and normal smooth muscle cells. The adventitia was normal and completely intact in all sections with no media/adventitia separation or perforations. Scanning electron microscopy revealed endothelial peeling, etching from the atherectomy devices within the smooth muscle layer, and a tapered atherectomy distal endpoint. The arterial branches were preserved without evidence of any disruption of the branch artery orifice. Compared to balloon angioplasty and laser angioplasty, the Rotoblator atherectomy device appears to leave a smoother, more rounded luminal surface that may result in less risk of embolic complications and arterial wall damage.