Revascularization Of Ischemic Limbs Research Articles

The Vascular architecture. Phlebosomes do they exist ?

The angiosome is a 3D structure which is perfused by a single perforating artery (arteriosome) and drained by a perforating vein (venosome). The concept of arteriosome is applied in plastic surgery and in the revascularization of ischemic limbs. Each venosome is also drained by longitudinal veins running in the subcutaneous layer. Accordingly, the concept of venosome cannot be applied in the field of the venous disorders of the limbs. The concept of phlebosome consider both paths of venous drainage.

Epigenetic profile of human adventitial progenitor cells correlates with therapeutic outcomes in a mouse model of limb ischemia.

We investigated the association between the functional, epigenetic, and expressional profile of human adventitial progenitor cells (APCs) and therapeutic activity in a model of limb ischemia. Antigenic and functional features were analyzed throughout passaging in 15 saphenous vein (SV)-derived APC lines, of which 10 from SV leftovers of coronary artery bypass graft surgery and 5 from varicose SV removal. Moreover, 5 SV-APC lines were transplanted (8×10(5) cells, IM) in mice with limb ischemia. Blood flow and capillary and arteriole density were correlated with functional characteristics and DNA methylation/expressional markers of transplanted cells. We report successful expansion of tested lines, which reached the therapeutic target of 30 to 50 million cells in ≈10 weeks. Typical antigenic profile, viability, and migratory and proangiogenic activities were conserved through passaging, with low levels of replicative senescence. In vivo, SV-APC transplantation improved blood flow recovery and revascularization of ischemic limbs. Whole genome screening showed an association between DNA methylation at the promoter or gene body level and microvascular density and to a lesser extent with blood flow recovery. Expressional studies highlighted the implication of an angiogenic network centered on the vascular endothelial growth factor receptor as a predictor of microvascular outcomes. FLT-1 gene silencing in SV-APCs remarkably reduced their ability to form tubes in vitro and support tube formation by human umbilical vein endothelial cells, thus confirming the importance of this signaling in SV-APC angiogenic function. DNA methylation landscape illustrates different therapeutic activities of human APCs. Epigenetic screening may help identify determinants of therapeutic vasculogenesis in ischemic disease.

Contemporary Evaluation and Management of the Diabetic Foot

Foot problems in patients with diabetes remain a major public health issue and are the commonest reason for hospitalization of patients with diabetes with prevalence as high as 25%. Ulcers are breaks in the dermal barrier with subsequent erosion of underlying subcutaneous tissue that may extend to muscle and bone, and superimposed infection is a frequent and costly complication. The pathophysiology of diabetic foot disease is multifactorial and includes neuropathy, infection, ischemia, and abnormal foot structure and biomechanics. Early recognition of the etiology of these foot lesions is essential for good functional outcome. Managing the diabetic foot is a complex clinical problem requiring a multidisciplinary collaboration of health care workers to achieve limb salvage. Adequate off-loading, frequent debridement, moist wound care, treatment of infection, and revascularization of ischemic limbs are the mainstays of therapy. Even when properly managed, some of the foot ulcers do not heal and are arrested in a state of chronic inflammation. These wounds can frequently benefit from various adjuvants, such as aggressive debridement, growth factors, bioactive skin equivalents, and negative pressure wound therapy. While these, increasingly expensive, therapies have shown promising results in clinical trials, the results have yet to be translated into widespread clinical practice leaving a huge scope for further research in this field.

Adiponectin promotes revascularization of ischemic muscle through a cyclooxygenase 2-dependent mechanism.

Adiponectin is a fat-derived plasma protein that has cardioprotective roles in obesity-linked diseases. Because cyclooxygenase 2 (COX-2) is an important modulator of endothelial function, we investigated the possible contribution of COX-2 to adiponectin-mediated vascular responses in a mouse hind limb model of vascular insufficiency. Ischemic insult increased COX-2 expression in endothelial cells of wild-type mice, but this induction was attenuated in adiponectin knockout mice. Ischemia-induced revascularization was impaired in mice in which the Cox-2 gene is deleted in Tie2-Cre-expressing cells. Adenovirus-mediated overexpression of adiponectin enhanced COX-2 expression and revascularization of ischemic limbs in control mice, but not in targeted Cox-2-deficient mice. In cultured endothelial cells, adiponectin protein increased COX-2 expression, and ablation of COX-2 abrogated the adiponectin-stimulated increases in endothelial cell migration, differentiation, and survival. Ablation of calreticulin (CRT) or its adaptor protein CD91 diminished adiponectin-stimulated COX-2 expression and endothelial cell responses. These observations provide evidence that adiponectin promotes endothelial cell function through CRT/CD91-mediated increases in COX-2 signaling. Thus, disruption of the adiponectin-COX-2 regulatory axis in endothelial cells could participate in the pathogenesis of obesity-related vascular diseases.

Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity

AbstractThe development of cell therapies to treat peripheral vascular disease has proven difficult because of the contribution of multiple cell types that coordinate revascularization. We characterized the vascular regenerative potential of transplanted human bone marrow (BM) cells purified by high aldehyde dehydrogenase (ALDHhi) activity, a progenitor cell function conserved between several lineages. BM ALDHhi cells were enriched for myelo-erythroid progenitors that produced multipotent hematopoietic reconstitution after transplantation and contained nonhematopoietic precursors that established colonies in mesenchymal-stromal and endothelial culture conditions. The regenerative capacity of human ALDHhi cells was assessed by intravenous transplantation into immune-deficient mice with limb ischemia induced by femoral artery ligation/transection. Compared with recipients injected with unpurified nucleated cells containing the equivalent of 2- to 4-fold more ALDHhi cells, mice transplanted with purified ALDHhi cells showed augmented recovery of perfusion and increased blood vessel density in ischemic limbs. ALDHhi cells transiently recruited to ischemic regions but did not significantly integrate into ischemic tissue, suggesting that transient ALDHhi cell engraftment stimulated endogenous revascularization. Thus, human BM ALDHhi cells represent a progenitor-enriched population of several cell lineages that improves perfusion in ischemic limbs after transplantation. These clinically relevant cells may prove useful in the treatment of critical ischemia in humans.

Is lower extremity revascularization worthwhile in patients with end-stage renal disease?

Background. The purpose of this study was to review the results of lower extremity revascularization in patients with end-stage renal disease and to determine in these patients the functional benefit and cost of an aggressive approach to limb preservation. Methods. During a 5-year period at our institution, 33 bypass operations were performed on 31 limbs of 23 dialysis-dependent patients. Indications for revascularization were limited (18) or extensive (12) tissue loss or ischemia without tissue loss (3). Procedures included aortobifemoral bypass (1), femoropopliteal bypass (10), and femorotibial/pedal bypass (22). A digital or transmetatarsal amputation was performed in 57% of limbs. Results. The 30-day primary patency was 100%. Cumulative primary and secondary patency rates at 2 years were 65% and 79%, respectively. Limb salvage was 67% and 59% at 1 and 2 years, respectively. Patient survival was poor (47% at 2 years). Peritoneal dialysis was predictive of poor survival (P <.001). Four of 5 patients on peritoneal dialysis died within 3 months of intervention. Extensive tissue loss was predictive of a diminished rate of limb salvage (P =.027). Only 39% of limbs with extensive tissue loss were salvaged at 1 year compared with 78% and 100% of limbs with limited and no tissue loss, respectively. The average hospital cost was $44,308 per year of limb salvage. Conclusions. Although revascularization of ischemic limbs in dialysis patients can be achieved with an excellent initial graft patency and reasonable limb salvage, patient survival is poor and costs are high. A selective approach to revascularization in these complicated patients may be indicated. For patients treated with peritoneal dialysis and for those with extensive tissue loss, primary amputation may be the preferred approach. (Surgery 2000;128:472–9.)

Semiclosed Transfemoral Iliac Endarterectomy with an Oscillating Ring Stripper

The technique of endarterectomy for the removal of occlusive atherosclerotic lesions of the aorta and iliac arteries has been utilized successfully in the revascularization of ischemic limbs since its introduction in 1951. The oscillating loop endarterectomy device (Amsco-Hall arterial oscillator) has proven to be useful for endarterectomy of segmental occlusive disease as a substitute for bypass with prosthetic graft. For our elderly debilitated patients, we have adopted a new technique of semiclosed transfemoral iliac endarterectomy for management of occlusive external iliac disease with a patent common iliac artery. We report seven patients treated during May 1987 through May 1988 for external iliac artery occlusion by transfemoral oscillating loop endarterectomy. At 12 months for follow-up review, the cumulative limb salvage rate was 80% with no perioperative mortality. One patient required above-knee amputation eight months following endarterectomy to control forefoot sepsis. Two patients required subsequent leg bypass procedures to achieve full healing of foot level amputation. One patient required dilatation of residual stenosis at the iliac bifurcation by percutaneous balloon angioplasty. Semiclosed transfemoral endarterectomy with the Amsco-Hall oscillating loop device remains an attractive option to the vascular surgeon for recanalization of the iliac artery without the need for an extensive retroperitoneal dissection.

Blunt popliteal artery trauma: one hundred consecutive injuries.

An institutional experience with 100 consecutive blunt popliteal artery injuries over a 20-year period was reviewed. The overall amputation rate was 15%; however, during the past 7 years this has declined from 23% to 6%. Minimizing delay in the revascularization of ischemic limbs, routine systemic heparinization, primary arterial repair when possible, repair of popliteal venous injuries, aggressive wound debridement, and early soft tissue coverage have contributed to improved limb salvage during the 1980s.

Blunt popliteal artery trauma: One hundred consecutive injuries

An institutional experience with 100 consecutive blunt popliteal artery injuries over a 20-year period was reviewed. The overall amputation rate was 15%; however, during the past 7 years this has declined from 23% to 6%. Minimizing delay in the revascularization of ischemic limbs, routine systemic heparinization, primary arterial repair when possible, repair of popliteal venous injuries, aggressive wound debridement, and early soft tissue coverage have contributed to improved limb salvage during the 1980s.