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Limb ischemia, acute [keywords]
- Arterial embolism. [Journal Article]
- Int J Crit Illn Inj Sci 2013 Jan; 3(1):77-87.
Surgical and intensive care patients are at a heightened risk for arterial embolization due to pre-existing conditions such as age, hypercoagulability, cardiac abnormalities and atherosclerotic disease. Most arterial emboli are clots that originate in the heart and travel to distant vascular beds where they cause arterial occlusion, ischemia, and potentially infarction. Other emboli form on the surface of eroded arterial plaque or within its lipid core. Thromboemboli are large clots that dislodge from the surface of athesclerotic lesions and occlude distal arteries causing immediate ischemia. Atheroemboli, which originate from fracturing the lipid core tend to cause a process of organ dysfunction and systemic inflammation, termed cholesterol embolization syndrome. The presentation of arterial emboli depends on the arterial bed that is affected. The most common manifestations are strokes and acute lower limb ischemia. Less frequently, emboli target the upper extremities, mesenteric or renal arteries. Treatment involves rapid diagnosis, which may be aided by precise imaging studies and restoration of blood flow. The type of emboli, duration of presentation, and organ system affected determines the treatment course. Long-term therapy includes supportive medical care, identification of the source of embolism and prevention of additional emboli. Patients who experienced arterial embolism as a result of clots formed in the heart should be anticoagulated. Arterial emboli from atherosclerotic disease of the aorta or other large arteries should prompt treatment to reduce the risk for atherosclerotic progression, such as anti-platelet therapy and the use of statin drugs. The use of anticoagulation and surgical intervention to reduce the risk of arterial embolization from atherosclerotic lesions is still being studied.
- Outcomes of lower extremity bypass performed for acute limb ischemia. [JOURNAL ARTICLE]
- J Vasc Surg 2013 May 25.
OBJECTIVE:Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia.
METHODS:All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year.
RESULTS:Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function, and respiratory complications. Patients who underwent lower extremity bypass for acute limb ischemia had no difference in rates of graft occlusion (18.1% vs 18.5%; P = .77), but did have significantly higher rates of limb loss (22.4% vs 9.7%; P < .0001) and mortality (20.9% vs 13.1%; P < .0001) at 1 year. On multivariable analysis, acute limb ischemia was an independent predictor of both major amputation (hazard ratio, 2.16; confidence interval, 1.38-3.40; P = .001) and mortality (hazard ratio, 1.41; confidence interval, 1.09-1.83; P = .009) at 1 year.
CONCLUSIONS:Patients who present with acute limb ischemia represent a less medically optimized subgroup within the population of patients undergoing lower extremity bypass. These patients may be expected to have more complex operations followed by increased rates of perioperative adverse events. Additionally, despite equivalent graft patency rates, patients undergoing lower extremity bypass for acute ischemia have significantly higher rates of major amputation and mortality at 1 year.
- Heparin-Induced Thrombocytopenia With Abdominal Aortic Stent-Graft Acute Thrombosis. [JOURNAL ARTICLE]
- Ann Vasc Surg 2013 May 24.
We report a case of heparin-induced thrombocytopenia in a patient on low molecular weight heparin bridge therapy who developed acute abdominal aortic stent-graft thrombosis 1 week after uncomplicated endovascular abdominal aortic aneurysm repair. The diagnosis was confirmed by a computed tomographic scan of the abdomen. The patient was successfully treated by conversion to open repair. The postoperative course was marked by subacute left limb ischemia related to an in vivo cross-reactivity of danaparoid with the heparin immune complex. To our knowledge, this is the first case report of heparin-induced thrombocytopenia with acute abdominal aortic stent-graft thrombosis.
- Acute lethal crush-injured rats can be successfully rescued by a single injection of high-dose dexamethasone through a pathway involving PI3K-Akt-eNOS signaling. [JOURNAL ARTICLE]
- J Trauma Acute Care Surg 2013 May 22.
BACKGROUND:Crush syndrome (CS) is characterized by ischemia/reperfusion-induced rhabdomyolysis and the subsequent onset of systemic inflammation. CS is associated with a high mortality, even when patients are treated with conventional therapy. We hypothesized that treatment of lethal CS rat model with dexamethasone (DEX) have therapeutic effects on the laboratory findings and clinical course and outcome.
METHODS:To create a CS model, anesthetized rats were subjected to bilateral hind limb compression with rubber tourniquets for 5 hours and randomly divided into three groups as follows: saline-treated CS group, CS groups treated with low (0.1 mg/kg) and high doses (5.0 mg/kg) of DEX. Saline for the CS group or DEX for the DEX-treated CS groups was intravenously administered immediately before reperfusion. Under continuous monitoring and recording of arterial blood pressures, blood and tissue samples were collected for histologic and biochemical analysis at designated period before and after reperfusion.
RESULTS:Ischemic compression of rat hind limbs reduced the nitrite content in the crushed muscle, and the subsequent reperfusion induced reactive oxygen species-mediated circulatory collapse and systemic inflammation, finally resulting in a mortality rate of 76% by 48 hours after reperfusion. A single injection of high-dose DEX immediately before reperfusion activated endothelial nitric oxide synthase (eNOS) by sequential phosphorylation through the nongenomic phosphoinositide 3-kinase (PI3K)-Akt-eNOS signaling pathway. DEX also exhibited anti-inflammatory effects by modulating proinflammatory and anti-inflammatory mediators, consequently suppressing myeloperoxidase activities and subsequent systemic inflammation, showing a complete recovery of the rats from lethal CS.
CONCLUSION:These results indicate that high-dose DEX reduces systemic inflammation and contributes to the improved survival rate in a rat CS model.
- Safety of Direct Cardiac Administration of AdVEGF-All6A+, a Replication-Deficient Adenovirus Vector cDNA/Genomic Hybrid Expressing All Three Major Isoforms of Human Vascular Endothelial Growth Factor, to the Ischemic Myocardium of Rats. [Journal Article]
- Hum Gene Ther Clin Dev 2013 Mar; 24(1):38-46.
Abstract Coronary artery disease (CAD), a leading cause of mortality, is a chronic disease in which blood flow to the myocardium is obstructed, leading to ischemia. Although coronary artery stenting and surgical bypass are successful with localized coronary lesions, patients with diffuse CAD have only pharmacologic options. In a mouse ischemic hind-limb model, AdVEGF-All6A+, an Ad5 vector expressing the cDNA/genomic hybrid of the vascular endothelial growth factor (VEGF) gene (expressing isoforms, 121, 165, and 189) mediated recovery of blood flow at a dose of two logs less than that required with a single isoform. The objective of the current study was to ascertain the safety profile of good manufacturing practice (GMP)-grade AdVEGF-All6A+ in the adult rat ischemic heart model in support of a clinical study to treat humans with diffuse CAD. AdVEGF-All6A+ (10(5), 10(6), or 10(7) particle units), a control vector (AdNull, 10(7) particle units) with no translatable expression cassette and a vehicle sham control (phosphate buffered saline [PBS]) were administered separately to the left ventricle of rats immediately following acute coronary artery ligation to initiate myocardial infarction (MI), designed to evoke an extreme ischemic myocardium in cohorts (n=5 males; n=5 females), with sacrifice at 5, 14, or 30 days. Six cohorts received no ligation but were administered AdVEGF-All6A+ vector or PBS with sacrifice at 30 or 365 days. Although there were surgical-related abnormalities among the groups, blinded evaluation of gross and histopathology, complete blood count, and serum chemistry found no significant differences between control- and vector-treated groups and no adverse effects could be attributed to AdVEGF-All6A+. No changes in serum troponin-I levels persisted beyond those associated with the MI. Gross pathology and histopathology of all major organs showed no AdVEGF-All6A+-related changes. Overall, this safety profile suggests that AdVEGF-All6A+ or AdNull administration to the myocardium meets the criteria to proceed to clinical trial.
- Bilateral toe necrosis resulting from norepinephrine bitartrate usage. [Journal Article]
- Adv Skin Wound Care 2013 Jun; 26(6):254-6.
Acute limb ischemia may manifest by ischemic rest pain, ischemic ulcers, or gangrene. Acute arterial occlusion can be the result of emboli from a distant source, acute thrombosis of a previously patent artery, or direct trauma to an artery. Toe necrosis resulting from norepinephrine bitartrate (Levophed; Hospira Inc, Lake Forest, Illinois) is a rare case.
- Safety and Efficacy of Ultra-high-dose, Short-term Thrombolysis with rt-PA for Acute Lower Limb Ischemia. [JOURNAL ARTICLE]
- Eur J Vasc Endovasc Surg 2013 May 15.
OBJECTIVES:The evaluation of success and complication rates of ultra high-dose recombinant tissue plasminogen activator (rt-PA) administered over a short time frame in the treatment of acute lower limb ischemia.
METHODS:This was a prospective single-center study. The outcome of treatment in 97 patients with acute limb ischemia (<14 days) with the use of catheter directed rt-PA infusion was evaluated. The mean total dose of rt-PA was 54.1 mg (50-60 mg) and was administered for a mean of 2.51 hours (2-4 hours). Thrombolytic success was defined as 95% thrombolysis of an occluded segment with return of antegrade flow. Thirty-day complication and amputation-free survival rates were calculated.
RESULTS:Thrombolytic success was achieved in 83.5%. Overall clinical success was 88.7%. The 30-day amputation-free survival rate was 93.8%. Major bleeding complications occurred in 10 patients (10.3%). There were two deaths (2.1%) and four amputations (4.1%). Long-term amputation-free survival was 70%.
CONCLUSIONS:Administration of ultra-high doses of rt-PA over a short time period gives promising results. Such delivery improves patient tolerance by rapid restoration of limb perfusion; however further studies are required to confirm these results.
- Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps. [JOURNAL ARTICLE]
- J Vasc Surg 2013 May 14.
OBJECTIVE:Ischemia-reperfusion (IR) injury is a significant problem in the management of patients with acute limb ischemia. Despite rapid restoration of blood flow after technically successful open and endovascular revascularization, complications secondary to IR injury continue to occur and limit clinical success. Our aim was to create a murine model of hind limb IR injury to examine the role of Toll-like receptor-4 (TLR4) and to determine whether inactive TLR4 led to a decrease in the detection of neutrophil extracellular traps (NETs), which are known to be highly thrombogenic and may mediate microvascular injury.
METHODS:A calibrated tension tourniquet was applied to unilateral hind limb of wild-type (WT) and TLR4 receptor mutant (TLR4m) mice for 1.5 hours to induce ischemia and then removed to initiate reperfusion. At the end of 48 hours of reperfusion, mice were euthanized and hind limb tissue and serum specimens were collected for analysis. Hematoxylin and eosin-stained sections of hind limb skeletal muscle tissue were examined for fiber injury. For immunohistochemistry, mouse monoclonal antihistone H2A/H2B/DNA complex antibody to detect NETs and rabbit polyclonal antimyeloperoxidase antibody were used to identify infiltrating cells containing myeloperoxidase. Muscle adenosine triphosphate levels, nuclear factor (NF)-κB activity, the α-subunit of inhibitor of NF-κB light polypeptide gene enhancer, poly (adenosine diphosphate-ribose) polymerase activity, and inducible nitric oxide synthase expression were measured. Systemic levels of keratinocyte-derived chemokine, monocyte chemotactic protein-1, and vascular endothelial growth factor in the serum samples were also examined.
RESULTS:IR injury in the hind limb of WT mice demonstrated significant levels of muscle fiber injury, decreased energy substrates, increased NF-κB activation, decreased levels of α-subunit of inhibitor of NF-κB light polypeptide gene enhancer, increased inducible nitric oxide synthase expression, and increased poly (adenosine diphosphate-ribose) polymerase activity levels compared with the TLR4m samples. Additionally, there was marked decrease in the level of neutrophil and monocyte infiltration in the TLR4m mice, which corresponded to similar levels of decreased NET detection in the interstitial space and in microvascular thrombi. In situ nuclease treatment of WT tissue sections significantly diminished the level of NET immunostaining, demonstrating the specificity of the antibody to detect NETs and suggesting a potential role for nuclease treatment in IR injury.
CONCLUSIONS:These results suggest a pivotal role for TLR4 in mediating hind limb IR injury and suggest that NETs may contribute to muscle fiber injury.
- Clinical presentation and outcome after failed infrainguinal endovascular and open revascularization in patients with chronic limb ischemia. [JOURNAL ARTICLE]
- J Vasc Surg 2013 May 14.
OBJECTIVE:Failure of prior endovascular (EV) interventions for chronic limb ischemia has been reported to negatively affect patency and limb salvage after subsequent revascularization procedures. The goal of our study was to compare the clinical presentation of patients who failed infrainguinal EV and open revascularizations (OR) and the effect of the initial intervention on final outcomes.
METHODS:From June 2001 to October 2010, 216 patients (237 limbs; 66 disabling claudication [DC], 171 critical limb ischemia [CLI]) presented with failed infrainguinal OR or EV revascularization for chronic limb ischemia. Clinical presentation, reinterventions, patency and limb salvage rates, and final outcomes were analyzed.
RESULTS:The EV group (n = 143) had more diabetes (44% vs 57%; P = .048) and ulcers (26% vs 38%; P = .039), whereas the OR group (n = 94) had more multilevel revascularizations (59% vs 33%; P < .001), rest pain (23% vs 9%; P = .002), and infrapopliteal interventions (58% vs 38%; P = .038). Presentation at time of failure was non-limb-threatening ischemia in 70% of DC and 16% of CLI patients (P < .001), with no difference in those initially treated with EV or OR. In CLI, 23% presented with acute limb ischemia in the OR group vs 10% in the EV group (P = .024). Early failure (<3 months) occurred in 15% of DC and in 36% of CLI patients and was more in the OR than in the EV group (30% vs 7% for DC [P = .011] and 71% vs 38% for CLI [P = .024]). Overall, 195 (82%) had attempted reinterventions (79% in DC and 85% in CLI; P = .245). In DC patients, 48% of OR had OR + EV and 26% had EV; 32% of EV had OR + EV and 47% had EV reinterventions. In CLI patients, 40% of OR had OR + EV and 42% had EV; 17% of EV had OR + EV; and 70% had EV reinterventions. A patent revascularized limb was achieved in 66% of OR and in 92% of EV patients (P < .001). Patency and limb salvage were significantly better in the EV group, mainly due to the difference in CLI patients, whereas survival was identical.
CONCLUSIONS:Clinical presentation after failed infrainguinal revascularization is determined by the initial indication. CLI patients are more likely to present early with acute limb ischemia, especially after OR. EV reinterventions play a significant role in the management of patients with failed revascularization, and EV failure is associated with better outcomes than those after OR failure, likely due to OR patients having more disadvantaged anatomy and advanced disease at the time of their initial presentation.
- Acute limb ischemia: Role of preoperative and postoperative duplex in differentiating acute embolic from thrombotic ischemia. [JOURNAL ARTICLE]
- Cardiovasc Revasc Med 2013 May 13.