Barend Mees

Microparticles From Ischemic Muscle Promotes Postnatal Vasculogenesis

Background— We hypothesized that microparticles (MPs) released after ischemia are endogenous signals leading to postischemic vasculogenesis. Methods and Results— MPs from mice ischemic hind-limb muscle were detected by electron microscopy 48 hours after unilateral femoral artery ligation as vesicles of 0.1- to 1-&mgr;m diameter. After isolation by sequential centrifugation, flow cytometry analyses showed that the annexin V+ MP concentration was 3.5-fold higher in ischemic calves than control muscles (1392±406 versus 394±180 annexin V+ MPs per 1 mg; P<0.001) and came mainly from endothelial cells (71% of MPs are CD144+). MPs isolated from ischemic muscles induced more potent in vitro bone marrow–mononuclear cell (BM-MNC) differentiation into cells with endothelial phenotype than those isolated from control muscles. MPs isolated from atherosclerotic plaques were ineffective, whereas those isolated from apoptotic or interleukin-1&bgr;–activated endothelial cells also promoted BM-MNC differentiation. Interestingly, MPs from ischemic muscles produced more reactive oxygen species and expressed significantly higher levels of NADPH oxidase p47 (6-fold; P<0.05) and p67 subunits (16-fold; P<0.001) than controls, whereas gp91 subunit expression was unchanged. BM-MNC differentiation was reduced by 2-fold with MPs isolated from gp91-deficient animals compared with wild-type mice (P<0.05). MP effects on postischemic revascularization were then examined in an ischemic hind-limb model. MPs isolated from ischemic muscles were injected into ischemic legs in parallel with venous injection of BM-MNCs. MPs increased the proangiogenic effect of BM-MNC transplantation, and this effect was blunted by gp91 deficiency. In parallel, BM-MNC proangiogenic potential also was reduced in ABCA1 knockout mice with impaired vesiculation. Conclusion— MPs produced during tissue ischemia stimulate progenitor cell differentiation and subsequently promote postnatal neovascularization.

Endothelial Nitric Oxide Synthase Overexpression Restores the Efficiency of Bone Marrow Mononuclear Cell-Based Therapy

Bone marrow-derived mononuclear cells (BMMNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. However, cardiovascular risk factors, including diabetes mellitus and hypercholesterolemia, lead to the abrogation of BMMNCs proangiogenic potential. NO has been shown to be critical for the proangiogenic function of BMMNCs, and increased endothelial NO synthase (eNOS) activity promotes vessel growth in ischemic conditions. We therefore hypothesized that eNOS overexpression could restore both the impaired neovascularization response and decreased proangiogenic function of BMMNCs in clinically relevant models of diabetes and hypercholesterolemia. Transgenic eNOS overexpression in diabetic, atherosclerotic, and wild-type mice induced a 1.5- to 2.3-fold increase in postischemic neovascularization compared with control. eNOS overexpression in diabetic or atherosclerotic BMMNCs restored their reduced proangiogenic potential in ischemic hind limb. This effect was associated with an increase in BMMNC ability to differentiate into cells with endothelial phenotype in vitro and in vivo and an increase in BMMNCs paracrine function, including vascular endothelial growth factor A release and NO-dependent vasodilation. Moreover, although wild-type BMMNCs treatment resulted in significant progression of atherosclerotic plaque in ischemic mice, eNOS transgenic atherosclerotic BMMNCs treatment even had antiatherogenic effects. Cell-based eNOS gene therapy has both proangiogenic and antiatherogenic effects and should be further investigated for the development of efficient therapeutic neovascularization designed to treat ischemic cardiovascular disease.

Tetrapeptide AcSDKP Induces Postischemic Neovascularization Through Monocyte Chemoattractant Protein-1 Signaling

Background—We investigated the putative proangiogenic activity and molecular pathway(s) of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in a model of surgically induced hindlimb ischemia. Methods and Results—Hindlimb ischemia was induced by femoral artery ligature and an osmotic minipump was implanted subcutaneously to deliver low (0.12 mg/kg per day) or high (1.2 mg/kg per day) doses of AcSDKP, for 7 or 21 days. Angiography scores, arteriole density, capillary number, and foot perfusion were increased at day 21 in the high-dose AcSDKP-treated mice (by 1.9-, 1.8-, 1.3-, and 1.6-fold, respectively) compared with control animals (P<0.05, P<0.01, P<0.01, respectively). AcSDKP treatment for 24 hours upregulated the monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels by 1.5-fold in cultured endothelial cells (P<0.01). In the ischemic hindlimb model, administration of AcSDKP also enhanced MCP-1 mRNA levels by 90-fold in ischemic leg (P<0.001) and MCP-1 plasma levels by 3-fold (P<0.001 versus untreated ischemic control mice). MCP-1 levels upregulation were associated with a 2.3-fold increase in the number of Mac3-positive cells in ischemic area of AcSDKP-treated mice (P<0.001 versus untreated animals). Interestingly, AcSDKP-induced monocyte/macrophage infiltration and postischemic neovascularization was fully blunted in MCP-1-deficient animals. Conclusion—AcSDKP stimulates postischemic neovascularization through activation of a proinflammatory MCP-1-related pathway.

Editor's Choice – Open Thoracic and Thoraco-abdominal Aortic Repair in Patients with Connective Tissue Disease

OBJECTIVE/BACKGROUNDnThe aim is to present current results of open complex aortic repair in patients with connective tissue disease (CTD).nnnMETHODSnThis was a retrospective cross-border, single centre study. From February 2000 to April 2016 72 aortic operations were performed on 65 patients with CTD (41 male, median age 41 years [range 19-70 years]). Fifty-six patients (86%) underwent at least one previous aortic repair (71 open, four endovascular), including 33 patients (51%) operated before at the site of the procedure reported here. The open procedures, counting eight emergency operations (11%), included aortic arch revision (nxa0=xa01; 1%), descending thoracic aortic repair (nxa0=xa011; 15%), TAAA type I repair (nxa0=xa012; 17%), type II repair (nxa0=xa029; 40%), type III repair (nxa0=xa012; 17%), and type IV repair (nxa0=xa05; 7%). Simultaneous repair of the ascending aorta and/or the aortic arch was performed in two (3%) and eight cases (11%), respectively. Seven patients (10%) underwent staged procedures. Median follow-up was 42 months (0.5-180 months).nnnRESULTSnThe in hospital mortality was 14% (nxa0=xa09) as a result of haemorrhage (nxa0=xa03/9), neurological (nxa0=xa03/9),xa0cardiac (nxa0=xa02/9), and pulmonary (nxa0=xa01/9) complications. Paraplegia and paraparesis occurred in one (2%) and three patients (5%), respectively. Seven patients (11%) required temporary dialysis; nonexa0needed permanent dialysis. Major complications were revision surgery for bleeding or haematoma (nxa0=xa020/65),xa0sepsis (nxa0=xa010/65), myocardial infarction/severe cardiac arrhythmia (nxa0=xa02/65), stroke (nxa0=xa02/65),xa0as well as multiorgan failure, abdominal compartment syndrome, mesenteric and peripheral ischaemia (all nxa0=xa01/65). Multivariate analysis identified an operating time >xa07xa0hours (pxa0=xa0.006) as an independent predictor of increased mortality. Freedom from re-intervention was 85%, 1 year survival was 80%, and overall survival was 75%.nnnCONCLUSIONnOpen TAA(A) repair is a durable therapy for patients with CTD. Often being performed as revision surgery, it can be associated with relevant risks and should therefore be reserved for specialised centres. Staged procedures and thus reducing operating time, if applicable, should be preferred.

Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice

PurposeKnowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.Materials and MethodsAll interventional radiologists, vascular surgeons, and technicians wore personal dose meters (PDMs, DoseAware, Philips Healthcare). The dose monitoring system simultaneously registered for each procedure dose-related data as the dose area product (DAP) and effective staff dose (E) from PDMs. Use and type of shielding were recorded separately. All procedures were analyzed according to procedure type; these included among others cerebral interventions (nxa0=xa0112), iliac and/or caval venous recanalization procedures (nxa0=xa068), endovascular aortic repair procedures (nxa0=xa063), biliary duct interventions (nxa0=xa058), and percutaneous gastrostomy procedure (nxa0=xa028).ResultsMedian (±IQR) DAP doses ranged from 2.0 (0.8–3.1) (percutaneous gastrostomy) to 84 (53–147) Gyxa0cm2 (aortic repair procedures). Median (±IQR) first operator doses ranged from 1.6 (1.1–5.0)xa0μSv to 33.4 (12.1–125.0) for these procedures, respectively. The relative exposure, determined as first operator dose normalized to procedural DAP, ranged from 1.9 in biliary interventions to 0.1xa0μSv/Gyxa0cm2 in cerebral interventions, indicating large variation in staff dose per unit DAP among the procedure types.ConclusionReal-time dose monitoring was able to identify the types of interventions with either an absolute or relatively high staff dose, and may allow for specific optimization of radiation protection.

Radial Artery Bypass Graft Is a Feasible and Durable Conduit for Challenging Infrainguinal Revascularization: 17 Years of Melbourne Experience

OBJECTIVESnThe superiority of autogenous venous conduits in infrainguinal bypass surgery is well established. In the absence of suitable leg or arm veins the radial artery can be utilized as an alternative autogenous conduit. In contrast to cardiac surgery, experience with the radial artery as a conduit for infrainguinal bypass surgery is limited. The purpose of this study was to review the outcomes of our radial artery bypasses over the last 17 years.nnnMETHODSnAll radial artery bypasses performed between 1995 and 2012 were identified from a prospective database. Patency, limb salvage, and survival were calculated using the Kaplan-Meier survival estimate method.nnnRESULTSnTwenty-nine radial artery bypasses were performed in 28 patients. Median follow-up was 55 months (range 1-170). Twelve-month primary, assisted primary, and secondary patency rates were 49%, 62%, and 73% respectively; Both 3-year and 5-year primary, assisted primary, and secondary patency rates were 49%, 56% and 67% respectively. Limb salvage rate was 75% at 1- and 5-year follow-up. Patient survival at 1, 3, and 5 years was 96%, 88%, and 76%.nnnCONCLUSIONSnFor patients with need of challenging infrainguinal revascularization without suitable autogenous venous conduit, a radial artery bypass can be performed safely with favorable long-term patency and limb salvage rates.

Open Thoracic and Thoraco-abdominal Aortic Repair in Patients with Connective Tissue Disease

Retrospective cross-border, single centre study February 2000 to April 2016 72 aortic operations on 65 patients with CTD 41 male, median age 41 years [range 19–70 years] 56 patients (86%) with previous aortic repair (71 open, 4 endovascular) 33 patients (51%) operated before at the site of the procedure reported here Procedures: 8 emergency operations (11%) Aortic arch revision (n = 1; 1%) Descending thoracic aortic repair (n = 11; 15%) TAAA type I repair (n = 12; 17%), Type II repair (n = 29; 40%) Type III repair (n = 12; 17%) Type IV repair (n = 5; 7%). Ascending aorta and/or the aortic arch (n = 2; 3%) and (n = 8; 11%) 7 patients (10%) underwent staged procedures Median follow-up: 42 months (0.5–180 months)

Late neurological recovery of paraplegia after endovascular repair of an infected thoracic aortic aneurysm.

Spinal cord ischemia is a potentially devastating complication after thoracic endovascular aorta repair (TEVAR). Patients with spinal cord ischemia after TEVAR often develop paraplegia, which is considered irreversible, and have significant increased postoperative morbidity and mortality. We report the case of a patient with unusual late complete neurologic recovery of acute-onset paraplegia after TEVAR for an infected thoracic aortic aneurysm.

Editor's Choice – Open Thoracic and Thoraco-abdominal Aortic Repair After Prior Endovascular Therapy

OBJECTIVEnThe aim was to present current results of open thoracic and thoraco-abdominal aortic repair as secondary procedure after prior endovascular therapy.nnnMETHODSnThis was a retrospective cross border single centre study. From 2006 to July 2017 45 open thoracic aortic (TAA) or thoraco-abdominal aortic aneurysm (TAAA) operations were performed on 44 patients (median age 58 [15-80] years) as secondary surgery after previous endovascular therapy comprising TEVAR (nxa0=xa038; 86%), EVAR (nxa0=xa03; 7%), fenestrated EVAR (nxa0=xa01; 2%) and TEVAR plus EVAR (nxa0=xa01; 2%). Eleven patients (25%) had had previous open aortic surgery at the secondary surgery site. Indications for TAA(A) repair were Type I endoleak (nxa0=xa010; 23%), post-dissection aneurysm progression due to persisting false lumen perfusion (nxa0=xa08; 18%), proximal/distal disease progression (nxa0=xa016; 36%), device fracture/dislocation (nxa0=xa04; 9%), infection (nxa0=xa05; 11%), and initial endograft misplacement (nxa0=xa01; 2%). The operations included descending thoracic aortic repair (nxa0=xa013, 29%), TAAA Type I (nxa0=xa04; 9%), Type II (nxa0=xa05; 11%), Type III (nxa0=xa013; 29%), Type IV (nxa0=xa07; 16%), and Type V repair (nxa0=xa03; 7%) with simultaneous arch repair in 18% (nxa0=xa08). The median time to secondary surgery was 36 (2-168) months. The median follow up was 39 (3-118) months.nnnRESULTSnIn hospital mortality was 20% (nxa0=xa09) due to intra-operative aneurysm rupture, pneumonia induced sepsis, hemorrhagic cerebellar infarction, mesenteric ischaemia, broncho-esophageal fistula, and multiorgan failure (1/9) as well as haemorrhage (3/9). Estimated survival was 73% at 1 year and 71% overall. The most frequent complications were pneumonia (nxa0=xa019; 43%), bleeding requiring revision (nxa0=xa011; 25%) and sepsis (nxa0=xa014; 32%). Transient dialysis was required in 32% (nxa0=xa014), permanent dialysis in 6% (nxa0=xa02). Permanent spinal cord deficit (paraparesis) occurred in 6% (nxa0=xa02). Estimated freedom from aortic re-intervention was 86%.nnnCONCLUSIONnOpen TAA(A) repair as a secondary procedure after previous endovascular aortic therapy is an important treatment option even in the endovascular era. It represents a durable treatment that can produce respectable outcomes. Yet the peri-operative morbidity and mortality are relevant and a specialised team and infrastructure are mandatory for these complex procedures. Therefore, centralisation is required.

Endovascular repair of a 63-year-old complication: post-traumatic anterior tibial artery arteriovenous fistula.

A 74-year-old female presented with an incidentally detected arteriovenous fistula (AVF) arising from the left anterior tibial artery (ATA). She was referred following lumbar spinal surgery complicated by post-operative left leg pain. Her past history included left proximal tibiofibular fracture treated with open reduction and internal fixation (ORIF) at the age of 11 and a left total knee replacement at the age of 68. Clinical investigation demonstrated an aneurysmal left popliteal pulse, diminished pedal pulses and an infrapopliteal thrill palpable over the anterior compartment or the leg near the pretibial ORIF scar. Duplex ultrasonography and computed tomography angiogram (CTA) demonstrated the AVF arising from the proximal ATA, in the region of the previous ORIF, with diameters of 11 mm proximal to the AVF and tapering from 7 to 3 mm beyond the AVF. This was confirmed on selective angiography (Fig. 1). The patient underwent endovascular repair of the AVF with a left common femoral artery antegrade puncture and deployment of a 11 × 50 mm Gore (Flagstaff, AZ, USA) Viabahn expanded polytetrafluoroethylene covered self-expanding stent in the proximal ATA across the AVF site. This was selected to maximize conformation to tortuosity in the proximal ATA and reduce excessive oversizing in the distal ATA. Angiographic views demonstrated complete exclusion of the AVF (Fig. 2). There were no perioperative complications. At 6-month follow-up there was complete resolution of symptoms. CTA and duplex ultrasound confirmed a patent ATA stent with excluded AVF, and repair has been durable out to 3 years. Endovascular management of post-traumatic AVF of the lower limb with covered stent grafts is a recognized treatment technique. The use of stent grafts has been extensively documented in the iliofemoral region; however, few reports exist of its use in infrapopliteal lesions. To our knowledge this is the first case report of endovascular repair with a stent graft of a post-traumatic ATA AVF occurring as an orthopedic complication. At 63 years, it also documents the longest delay to presentation for a post-traumatic lower limb AVF, previously recorded by Huang et al. at 51 years. Traumatic fistulae of the ATA are uncommon. Described repair techniques include arterial ligation, primary repair with or without vein patch, and venous interposition grafting. Numerous minimally invasive management strategies have been described such as direct pressure, embolization with coils or balloons, thrombin injection and endovascular stenting. Of the other minimally invasive techniques available, direct pressure is ineffective for AVFs as the physical low-resistance outflow