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BACKGROUND Establishing central venous access is important to provide fluid resuscitation or medications intravenously to patients. OBSERVATIONS Although accidental cannulation of the internal carotid artery has been reported in the literature, to our knowledge this report is the first documented intraoperative ultrasound video demonstrating accidental and simultaneous common carotid artery and internal jugular cannulation during central line placement in the internal jugular vein. LESSONS Ultrasound use minimizes accidental carotid cannulation during central line placement in the internal jugular vein. Carotid artery puncture can be managed by external application of pressure or surgical reexploration.

Introduction: We showed that myoblasts (Mb) in peripheral arterial disease (PAD) differentiate poorly and have evidence of inflammasome activation. Absent-in-melanoma 2 (AIM2), an inflammasome and mediator of pyroptosis, binds damaged DNA which also triggers the G2/M DNA damage checkpoint including CDC2 and its regulator, polo-like kinase 1 (PLK1). Dysregulated checkpoints can cause faulty replication, but a link between checkpoint function and AIM2 is not known. We hypothesize that AIM2 expression in PAD Mb correlates with increased DNA damage and a dysregulated G2/M DNA damage checkpoint. Methods: Cells were harvested from ischemic and perfused muscle obtained during amputations for PAD. Mb (Pax7-/MyoD+) were isolated using sequential plating and cell sorting. Mb from healthy donors (PAD -) were purchased (Cook MyoSite®). AIM2, γH2AX (DNA damage marker), PLK1 and CDC2 were measured with immunofluorescence (5 images/dish). Mb were treated with the PLK1-inhibitor BI2536 (10nM; 1h) to assess checkpoint responsiveness. ANOVA with post-hoc analysis confirmed statistical significance (α=0.05). Results: γH2AX expression was elevated in all PAD groups compared to PAD (-) Mb (N=3-4/PAD group). While PLK1 expression was similar across groups, CDC2 was lower in all ischemic PAD groups relative to perfused PAD Mb. BI2536 attenuated CDC2 expression in perfused PAD Mb (p = 0.006) while Mb in ischemic PAD remained unresponsive. AIM2 expression was significantly higher in ischemic Mb compared to perfused and PAD (-) Mb, correlating with high γH2AX and low CDC2. Results are summarized in Figure 1. Conclusion: Here, we show that in PAD Mb, AIM2 correlates with DNA damage, attenuated DNA damage checkpoint protein expression and diminished CDC2 responsiveness to BI2536. Thus, AIM2 may promote pyroptosis in the setting of defective DNA damage mechanisms that would otherwise prompt apoptosis. Whether these pathways are reversed by revascularization is a topic of further study.

Multivisceral transplantation is a life-saving treatment for many chronically ill patients with advanced abdominal pathologies. For such transplants, a complex arterial reconstruction is required, with numerous anastomoses on a composite donor graft and the native aorta. In these patients, anastomotic disruption or pseudoaneurysm formation, often in the setting of infection, are deadly complications. Open surgical repair is hazardous, because many of these patients have dense adhesions. Reported cases of disruption at the aortic anastomosis to date have resulted in patient demise. We report the case of a pediatric multivisceral transplant recipient with ruptured aortic pseudoaneurysm. He underwent an emergent endovascular parallel stent grafting technique, which successfully controlled bleeding and maintained graft perfusion.

Although most work has focused on resolution of collagen ECM, fibrosis resolution involves changes to several ECM proteins. The purpose of the current study was two-fold: 1) to examine the role of MMP12 and elastin; and 2) to investigate the changes in degraded proteins in plasma (i.e., the “degradome”) in a preclinical model of fibrosis resolution. Fibrosis was induced by 4 weeks carbon tetrachloride (CCl4) exposure, and recovery was monitored for an additional 4 weeks. Some mice were treated with daily MMP12 inhibitor (MMP408) during the resolution phase. Liver injury and fibrosis was monitored by clinical chemistry, histology and gene expression. The release of degraded ECM peptides in the plasma was analyzed using by 1D-LC-MS/MS, coupled with PEAKS Studio (v10) peptide identification. Hepatic fibrosis and liver injury rapidly resolved in this mouse model. However, some collagen fibrils were still present 28d after cessation of CCl4. Despite this persistent collagen presence, expression of canonical markers of fibrosis were also normalized. The inhibition of MMP12 dramatically delayed fibrosis resolution under these conditions. LC-MS/MS analysis identified that several proteins were being degraded even at late stages of fibrosis resolution. Calpains 1/2 were identified as potential new proteases involved in fibrosis resolution. CONCLUSION. The results of this study indicate that remodeling of the liver during recovery from fibrosis is a complex and highly coordinated process that extends well beyond the degradation of the collagenous scar. These results also indicate that analysis of the plasma degradome may yield new insight into the mechanisms of fibrosis recovery, and by extension, new “theragnostic” targets. Lastly, a novel potential role for calpain activation in the degradation and turnover of proteins was identified.

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that decon-struction of the extracellular matrix is essential to the remodeling of smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of in-ternal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content is low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension as demonstrated by straight-ening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

Lower extremity arterial occlusive disease (AOD) results in significant morbidity and mortality for the population, with up to 10% of patients ultimately requiring amputation. An alternative method for non-surgical revascularization which is yet to be fully understood is the optimization of the body's own natural collateral arterial network in a process known as arteriogenesis. Under conditions of conductance vessel stenosis or occlusion resulting in increased flow, shear forces, and pressure gradients within collaterals, positive remodeling occurs to increase the diameter and capacity of these vessels. The creation of a distal arteriovenous fistula (AVF) will drive increased arteriogenesis as compared to collateral formation with the occlusion of a conductance vessel alone by further increasing flow through these arterioles, demonstrating the capacity for arteriogenesis to form larger, more efficient collaterals beyond what is spontaneously achieved after arterial occlusion. Arteries rely on an extracellular matrix (ECM) composed of elastic fibers and collagens that provide stability under hemodynamic stress, and ECM remodeling is necessary to allow for increased diameter and flow conductance in mature arterial structures. When positive remodeling occurs, digestion of lamella and the internal elastic lamina (IEL) by matrix metalloproteinases (MMPs) and other elastases results in the rearrangement and thinning of elastic structures and may be replaced with disordered elastin synthesis without recovery of elastic function. This results in transmission of wall strain to collagen and potential for aneurysmal degeneration along collateral networks, as is seen in the pancreaticoduodenal artery (PDA) after celiac occlusion and inferior mesenteric artery (IMA) with concurrent celiac and superior mesenteric artery (SMA) occlusions. Further understanding into the development of collaterals is required to both better understand aneurysmal degeneration and optimize collateral formation in AOD.

Arteriogenesis represents the maturation of preformed vascular connections in response to flow changes and shear stress. These collateral vessels can restore up to 60% of the native blood flow. Shear stress and vascular injury can induce the release of nucleotides from vascular smooth muscle cells and platelets that can serve as signaling ligands, suggesting they may be involved in mediating arteriogenesis. The P2Y2 nucleotide receptor (P2Y2R) has also been shown to mediate smooth muscle migration and arterial remodeling. Thus, we hypothesize that P2Y2R mediates arteriogenesis in response to ischemia.Hind limb ischemia was induced by femoral artery ligation (FAL) in C57Bl/6NJ or P2Y2R negative mice (P2Y2(-/-)). Hind limb perfusion was measured with laser Doppler perfusion imaging and compared with the sham-operated contralateral limb immediately and at 3, 7, 14, 21, and 28 days after ligation. Collateral vessel size was measured by Microfil casting. Muscle specimens were harvested and analyzed with immunohistochemistry for Ki67, vascular cell adhesion molecule, macrophages, and muscle viability by hematoxylin and essoin stain.Hind limb ischemia induced by FAL in C57Bl/6NJ mice resulted in significant ischemia as measured by laser Doppler perfusion imaging. There was rapid recovery to nearly normal levels of perfusion by 2 weeks. FAL in P2Y2(-/-) mice resulted in severe ischemia with greater tissue loss. Recovery of perfusion was impaired, achieving only 40% compared with wild-type mice by 28 days. Collateral vessels in the P2Y2(-/-) mice were underdeveloped, with reduced vascular cell proliferation and smaller vessel size. The collaterals were ∼65% the size of wild-type collateral vessels (P = .011). Angiogenesis at 28 days in the ischemic muscle, however, was greater in the P2Y2(-/-) mice (P.001), possibly related to persistent ischemia leading and angiogenic drive. Early macrophage recruitment was reduced by nearly 70% in P2Y2(-/-) despite significantly more myocyte necrosis. However, inflammation was greater at 28 days in the P2Y2(-/-) mice.P2Y2R deficiency does not alter baseline collateral vessel formation but does significantly impair collateral maturation, with resultant persistent limb ischemia despite enhanced angiogenesis. These findings reinforce the importance of arteriogenesis in the recovery of perfusion in ischemic tissues compared with angiogenesis. They also support the role of P2Y2R in mediating this process. The mechanism by which P2Y2R mediates arteriogenesis may involve the recruitment of inflammatory cells to the ischemic tissues, which is essential to arteriogenesis. Approaches to target P2Y2R may yield new therapeutic strategies for the treatment of arterial occlusive disease.

Purinergic signaling plays a role in vessel remodeling among developing collateral arteries. We have previously shown that the P2Y 2 receptor, an ATP/UTP receptor, mediates arteriogenesis in a murine model of hindlimb ischemia. Intra-arterial administration of UTP increases perivascular inflammation and macrophage accumulation, necessary early events of arteriogenesis, an effect which was abolished among P2Y 2 -/- mice. Extracellular nucleotides can be dephosphorylated by ectonuclotidases which are expressed in various tissues, converting ATP/UTP into ADP/UDP. Our objective was to identify whether receptors for these derivative nucleotides would also have a role in arteriogenesis. Muscular branches of the caudal femoral artery were explanted from rat and assessed for purinergic receptor expression by immunofluorescence. Baseline expression of P2Y 2 is found among endothelial cells predominantly. Conversely, the P2Y 6 receptor is highly expressed in the media, with no appreciable staining in the endothelium. CD39, an ectonucleotidase, is expressed among VSMCs in developing collateral arteries (Figure). We then sought to identify whether inhibition of the P2Y 6 receptor, the ligand for which is UDP, would alter perfusion recovery after femoral artery ligation (FAL). Selective P2Y 6 receptor antagonist MRS2578 was intraperitoneally delivered via osmotic minipump at a rate of 20 ng/hr. FAL was performed and perfusion recovery monitored over 14 days using laser Doppler perfusion imaging (LDPI). Perfusion recovery was reduced in animals treated with MRS2578 when compared to vehicle (DMSO) at 7 and 14 days (figure). Two (out of 12) animals receiving MRS2578 were euthanized due to gangrene of the hindlimb. We have demonstrated in this work that the P2Y 6 receptor is another mediator of arteriogenesis. Our results also suggest an interesting spatial localization of purinergic receptors among resident vascular cells which may facilitate their function in arteriogenesis.

Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H2O2, 0.15%) or allopurinol (30 μg) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H2O2 and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H2O2 restored wound healing in tungsten-fed mice. In vitro, nitrite and H2O2 both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production.

BACKGROUND Noncompressible hemorrhage of the torso remains a challenging surgical dilemma. Stent graft repair requires endovascular expertise, imaging, and inventory that are not available within the critical window of massive hemorrhage. We developed a retrievable stent graft for rapid hemorrhage. We further investigated a radiofrequency (RF) positioning approach as a possible alternative to the logistics of fluoroscopy. METHODS A retrievable stent graft was constructed with a novel "petal and stem" design from nitinol and covered with a sleeve of electrospun polyurethane. The stent graft was tested using an in vitro model of simulated hemorrhage. Next, the stent graft was examined in vivo using a porcine model of noncompressible hemorrhage. The stent was examined for hemorrhage control in a porcine model of either aortic or caval injury. An RF reader was assembled from an Arduino processor while RF tags were affixed to the ends of the stent graft. Detection accuracy of a handheld RF wand for an RF tag was quantified both in vitro and through tissue. RESULTS The retrievable RESCUEstent graft was deployed within minutes and rapidly controlled traumatic hemorrhage angiographically in both aortic injury (n = 3) and caval injury (n = 2). Stent grafts were easily recaptured in both models in under 15 seconds. The LED light of a handheld RF detector illuminated when positioned directly over an RF tag. The RF detection approach revealed positioning accuracy to within 1 cm of the intended target, despite tissue interference. CONCLUSION This study demonstrates the rapid deployment and retrieval of a RESCUE stent graft as well as the ability to tamponade injuries of the aorta and cava. In addition, this study demonstrates the feasibility of RF tags to guide stent placement through tissue. More rigorous models are needed to define the effectiveness of this approach in the setting of vascular injury and shock.

Nutcracker syndrome is a rare condition of left renal vein entrapment manifesting with hematuria, flank pain, and, occasionally, pelvic congestion in females or varicocele in males. Diagnosis requires a high index of suspicion upon careful history delineation. The gold standard for definite confirmation remains venography with renocaval pressure gradient. Treatment is mainly guided by the severity of symptoms. For the majority of centers, it appears that surgery remains the first-line therapy, however, endovascular alternatives are rapidly evolving into the field with favorable outcomes. This article reviews current concepts on nutcracker syndrome with particular focus on contemporary surgical and endovascular techniques and their outcomes.

ObjectiveEndovascular interventions for critical limb ischemia (CLI) continue to have variable reported results. The purpose of this study is to determine the effect of disease level and distribution on the outcomes of tibial interventions.MethodsA retrospective analysis of all tibial interventions done for CLI between 2006 and 2009 was performed. Outcomes of isolated tibial (group I) and multilevel interventions (group II) (femoropopliteal and tibial) were compared.ResultsEndovascular interventions were utilized to treat 136 limbs in 123 patients for CLI: 54 isolated tibial (85% tissue loss), and 82 multilevel (80% tissue loss). Mean age and baseline comorbidities were comparable. The mean ankle-brachial index (ABI) was significantly lower prior to intervention in group II (0.53 vs 0.74; P < .001) but was similar postintervention (0.86 vs 0.88; P = NS). Wound healing or improvement was achieved in 69% in group I and in 87% in group II (P = .05). Mean overall follow-up was 12.6 ± 5.3 months. Time to healing was significantly longer in group I: 11.5 ± 8.8 months vs 7.7 ± 6.6 months (P = .03). Limb salvage was achieved in 81% of group I and 95% of group II (P = .05). The rate of reintervention was similar (13% vs 18%, P = NS), so was the rate of late surgical conversion (0% vs 6%; P = NS). Limb loss resulted from lack of conduit or initial target vessel for bypass and high-risk systemic comorbidities. Overall mortality rates were similar among both groups. An isolated tibial intervention was a predictor of limb loss at 1 year on multivariate analysis and resulted in a lower rate of limb salvage at 1 year compared with multilevel interventions. Additionally, despite comparable primary patency rates, there was improved secondary patency with multilevel interventions compared with the isolated tibial interventions. Predictors of limb loss in patients treated with isolated tibial intervention included multiple synchronous tibial revascularization (P = .005) and advanced coronary artery disease requiring revascularization (P = .005).ConclusionsAdequate rates of limb salvage can be achieved in patients undergoing multilevel interventions for CLI, and improved patency is seen with multilevel compared to isolated tibial interventions. Patients with isolated tibial disease appear to have a higher incidence of limb loss secondary to poor initial pedal runoff, more extensive distal disease, and severe comorbidities precluding surgical bypass. Other therapeutic strategies should be considered in these patients, including primary amputation or pedal bypass when applicable.

Arteriogenesis (collateral artery development) is an adaptive pathway critical for salvage of tissue in the setting of arterial occlusion. Rodent models of arteriogenesis typically involve an experimental occlusion (ligation) of a hindlimb artery and then rely on indirect measures such as laser Doppler perfusion imaging to assess blood flow recovery. Unfortunately, the more commonly utilized measures of distal tissue perfusion at rest are unable to account for hemodynamic and vasoactive variables and thus provide an incomplete assessment of collateral network capacity. We provide a detailed description of modifications to the commonly used model of femoral artery ligation. These serve to alter and then directly assess collateral network’s hemodynamic capacity. By incorporating an arteriovenous fistula distal to the arterial ligation, arterial growth is maximized. Hindlimb perfusion may be isolated to measure minimum resistance of flow around the arterial occlusion, which provides a direct measure of collateral network capacity. Our results reinforce that arteriogenesis is driven by hemodynamic variables, and it can be reliably augmented and measured in absolute terms. Using these modifications to a widely used model, functional arteriogenesis may be more directly studied.

Objectives: Arteriogenesis is a process by which small resistance vessels mature into large caliber collateral arteries in response to arterial occlusive disease. Inflammatory cells of monocyte/macrophage lineage are necessary to promote vascular remodeling. We have previously reported that mice lacking the P2Y2 receptor, a purinergic receptor whose agonists include ATP and UTP, exhibited impaired collateral development and persistently reduced perfusion when subjected to femoral artery ligation (FAL). Thus, we hypothesize that purinergic signaling via the P2Y2 receptor mediates inflammatory cell recruitment during arteriogenesis. Methods: C57Bl6 mice underwent FAL and intra-arterial infusion of 200uL of PBS or 100uM UTP in PBS (N=3 each group). Hindlimb perfusion was assessed with laser Doppler imaging at day 7. In a separate experiment, P2Y2 -/- mice underwent femoral artery ligation alongside C57Bl/6 (wild type receptor) mice without UTP infusion. Thigh adductor muscles were fixed, sectioned, and immunostaining was performed for inflammatory cells (anti-CD45) and macrophages/monocytes (anti-F4/80). Two collateral vessels were analyzed per animal, and positive cells were quantified per high-power field. Results: UTP treated mice showed a trend toward increased peri-collateral CD45 positive cells at 12hr, and significantly increased F4/80 positive cells at day 3 (18.3+/-3.3 vs 11.5+/-1.3, p=0.044). This corresponded to improved perfusion at 7 days in UTP treated mice (58.5%+/-3.9 vs 36.0%+/-2.8, p=0.026). P2Y2 -/- mice recruited fewer F4/80 positive cells to the collateral vessels at day 3 when compared to the wild type (1.8 ± 1.3 vs 11.8 ± 2.9, p=.012). Conclusion: UTP treatment increases macrophage recruitment to the immature collateral vessel wall and improves perfusion recovery following FAL. In the absence of P2Y2 receptor, macrophage recruitment was significantly inhibited. These findings suggest that purinergic signaling via the P2Y2 receptor is an important mediator of vascular inflammation which is required for collateral growth. Ongoing studies will focus on the cellular mechanisms involved and whether enhanced collateral maturation and limb perfusion can be driven by the pharmacologic administration of nucleotides.

Objective Abdominal aortic aneurysms (AAA) affect up to 9% of men over 65 years of age with increasing incidence with further aging. Little is still known about the pathogenesis of AAA but inflammation appears to be one of the main contributing factors. Carbon monoxide (CO) is an endogenously produced molecule that has been shown to have significant anti-inflammatory and cytoprotective properties. Thus, we hypothesize that exogenous CO may attenuate AAA growth. Methods Eight week-old C57Bl6 mice were anesthetized and infrarenal aorta were exposed, measured in 3 locations, and treated with topical porcine pancreatic elastase (30 ul). Mice were either maintained in room air for the duration of the experiment or treated with inhaled CO (250 PPM) for 1 hr daily beginning on day 1. Animals were sacrificed on day 14 when aortic diameters were measured and tissues collected for morphometric analysis. Results Topical elastase treatment resulted in marked aortic enlargement with true aneurysm formation (253% of baseline, N=8). However, CO treatment reduced aneurysm size significantly (222%, N=8; p-0.039) with noticeable reduction in adhesion formation and scarring around the aorta. Histologically, CO treated animals maintained a larger medial area than controls (0.092 mm 2 vs 0.057 mm 2 ; p = 0.023) (Figure 1). Conclusion Inhaled CO appears to mitigate aneurysmal degeneration of the abdominal aorta induced by topical elastase. There was a clear reduction in adhesions to the aorta, strongly supporting the anti-inflammatory mechanism involved. The maintenance of a thicker medial component of the aorta in CO treated mice also suggests protection of the smooth muscle cells.

Objectives: Arteriogenesis is a process by which small resistance vessels mature into large caliber collateral arteries in response to arterial occlusive disease. The forces stimulating arteriogenesis nclude shear stress and circumferential wall stress. Nucleotides are released from cells in response to mechanical stimuli and may activate nucleotide receptors. Thus, we hypothesize that the P2Y 2 nucleotide receptor, expressed by vascular cells, mediates arteriogenesis. Methods: C57Bl6 NJ (WT) and P2Y 2 R KO mice (n=8/group) underwent unilateral femoral artery ligation (FAL). Perfusion was measured immediately after ligation and at 3, 7, 14, 21, and 28 days using laser Doppler perfusion imaging (LDPI). Mice were sacrificed at 28 days and tibialis anterior collected for histology. Results: LDPI of the ischemic hindlimb showed a return to baseline perfusion in WT mice (Figure). P2Y 2 KO mice recovered to 2 KO mice developed wounds of the ischemic limbs vs. 0/8 of WT mice. Histological analysis of tibialis anterior demonstrated regenerating myocytes in 3/4 P2Y 2 KO vs. 1/4 WT animals. By immunohistochemistry, angiogenesis was significantly increased in P2Y 2 KO with a CD31+cell/myocyte ratio of 1.974 vs. 1.314 of WT (p=0.05). There was also greater inflammation in P2Y 2 KO with CD45+ cell infiltration over 3-fold that of WT (pConclusion: The P2Y 2 nucleotide receptor is important for blood flow recovery in a murine model of FAL. P2Y 2 KO mice also demonstrated delayed muscle regeneration with greater angiogenesis and inflammation in ischemic limbs. Further molecular analyses are needed to elucidate the mechanisms involved.

The presence of a persistent sciatic artery is a rare congenital vascular malformation. Complications associated with aneurysmal degeneration of this aberrant vessel include rupture, thrombosis, and embolization with obliteration of outflow vessels. We describe the case of an 82-year-old female presenting with critical limb ischemia due to embolization from a partially thrombosed persistent sciatic artery aneurysm. Successful treatment was achieved via a common femoral to posterior tibial artery bypass with the great saphenous vein and vascular plug embolization of the aneurysm.

ObjectiveThe efficacy of tibial artery endovascular intervention (TAEI) for critical limb ischemia (CLI) and particularly for wound healing is not fully defined. The purpose of this study is to determine predictors of failure and success for TAEI in the setting of CLI.MethodsAll TAEI for tissue loss or rest pain (Rutherford classes 4, 5, and 6) from 2004 to 2008 were retrospectively reviewed. Clinical outcomes and patency rates were analyzed by multivariable Cox proportional hazards regression and life table analysis.ResultsOne hundred twenty-three limbs in 111 patients (62% male, mean age 74) were treated. Sixty-seven percent of patients were diabetics, 55% had renal insufficiency, and 21% required hemodialysis. One hundred two limbs (83%) exhibited tissue loss; all others had ischemic rest pain. All patients underwent tibial angioplasty (PTA). Tibial excimer laser atherectomy was performed in 14% of the patients. Interventions were performed on multiple tibial vessels in 20% of limbs. Isolated tibial procedures were performed on 50 limbs (41%), while 73 patients had concurrent ipsilateral superficial femoral artery or popliteal interventions. The mean distal popliteal and tibial runoff score improved from 11.8 ± 3.6 to 6.7 ± 1.6 (P < .001), and the mean ankle-brachial index increased from 0.61 ± 0.26 to 0.85 ± 0.22 (P < .001). Surgical bypass was required in seven patients (6%). The mean follow up was 6.8 ± 6.6 months, while the 1-year primary, primary-assisted, and secondary patency rates were 33%, 50%, and 56% respectively. Limb salvage rate at 1 year was 75%. Factors found to be associated with impaired limb salvage included renal insufficiency (hazard ratio [HR] = 5.7; P = .03) and the need for pedal intervention (HR = 13.75; P = .04). TAEI in an isolated peroneal artery (odds ratio = 7.80; P = .01) was associated with impaired wound healing, whereas multilevel intervention (HR = 2.1; P = .009) and tibial laser atherectomy (HR = 3.1; P = .01) were predictors of wound healing. In patients with tissue loss, 41% achieved complete closure (mean time to healing, 10.7 ± 7.4 months), and 39% exhibited partial wound healing (mean follow up, 4.4 ± 4.8 months) at last follow up. Diabetes, smoking, statin therapy, and revascularization of >1 tibial vessel had no impact on limb salvage or wound healing. Re-intervention rate was 50% at 1 year.ConclusionsTAEI is an effective treatment for CLI with acceptable limb salvage and wound healing rates, but requires a high rate of reintervention. Patients with renal failure, pedal disease, or isolated peroneal runoff have poor outcomes with TAEI and should be considered for surgical bypass.