Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/- mice.

BACKGROUND: We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. METHODS: Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. RESULTS: Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P < 0.0001). After exercise, plasma levels of vascular endothelial cell growth factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P < 0.004). The cytokines KC and MIP-2 in muscle were greater in exercised ApoE-/- mice compared with C57BL6 mice (P = 0.01). Increased poly-ADP-ribose activity and mature muscle regeneration were associated with demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). CONCLUSIONS: Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration.

Intermediate-term outcomes of endovascular treatment for symptomatic chronic mesenteric ischemia.

OBJECTIVE: Endovascular therapy for chronic mesenteric ischemia (CMI) has been increasingly utilized. Early outcomes compare favorably with open mesenteric bypass--the current gold standard. The goal of this study is documentation of intermediate-term anatomic and functional outcomes of endovascular mesenteric revascularization for symptomatic CMI. METHODS: This is a retrospective review of all patients undergoing endovascular treatment of symptomatic CMI from July 2002 to March 2008. Study endpoints included periprocedural mortality, major morbidity, patency, symptomatic recurrence, and survival. Endpoints were analyzed using actuarial methods. RESULTS: Sixty-six mesenteric arteries (78.8% stenotic/21.2% occluded) were treated in 49 patients. One or more vessels were treated in each case; however, four mesenteric artery total occlusions (3 SMAs/1 IMA) could not be crossed. Initial symptom relief was noted in 89.8% (n = 44) with no change in 5 patients. Single-vessel treatments were performed in 32 patients (65.3%) and two-vessel interventions in 17 (34.7%). The 30-day mortality rate was 2.0% (n = 1). Major complications occurred in 8 patients (16.3%). The mean follow-up duration was 37.4 +/- 2.98 months (range, 0-66). Restenosis on follow-up imaging occurred in 64.9% (n = 24) of the 37 patients who had radiographic surveillance at a mean follow-up interval of 8.5 +/- 1.9 months and was diagnosed most often by Duplex scan or computed tomographic angiography (CTA). Fourteen patients (28.6%) developed recurrent symptoms with 13 requiring a reintervention. Actuarial 36-month freedom from symptomatic recurrence was 60.9% +/- 9.4%. Two-vessel treatment was protective against symptom recurrence (P = .0014) and reintervention (P = .0060) by univariate analysis. A total of 19 reinterventions were required in 14 patients (28.6%) at a mean of 17 months from the original treatment. Primary patency at 36 months was 63.9 +/- 8.5%. Actuarial survival at 48 months was 81.1% +/- 6.1% with no CMI-related deaths in the study cohort. CONCLUSION: Intermediate (3-year) follow-up indicates that significant restenosis and symptom recurrence are common following the endovascular treatment of symptomatic CMI. Thirty percent of the cohort required a reintervention, one-third of which were conversions to surgical reconstruction. Similar to the surgical paradigm of two-vessel revascularization, endovascular treatment of multiple mesenteric arteries produced better outcomes. A first-line endovascular approach to patients with CMI is a reasonable clinical strategy, but close follow-up is mandatory.

A functional murine model of hindlimb demand ischemia.

BACKGROUND: To date, murine models of treadmill exercise have been used to study general exercise physiology and angiogenesis in ischemic hindlimbs. The purpose of these experiments was to develop a murine model of demand ischemia in an ischemic limb to mimic claudication in humans. The primary goal was to determine whether treadmill exercise reflected a hemodynamic picture which might be consistent with the hyperemic response observed in humans. METHODS: Aged hypercholesterolemic ApoE null mice (ApoE(-/-), n = 13) were subjected to femoral artery ligation (FAL) and allowed to recover from the acute ischemic response. Peripheral perfusion of the hindlimbs at rest was determined by serial evaluation using laser Doppler imaging (LDI) on days 0, 7, and 14 following FAL. During the experiments, mice were also assessed on an established five-point clinical ischemic score, which assessed the degree of digital amputation, necrosis, and cyanosis compared to the nonischemic contralateral limb. After stabilization of the LDI ratio (ischemic limb flux/contralateral nonischemic limb flux) and clinical ischemic score, mice underwent 2 days of treadmill training (10 min at 10 m/min, incline of 10 degrees ) followed by 60 min of daily treadmill exercise (13 m/min, incline of 10 degrees ) through day 25. An evaluation of preexercise and postexercise perfusion using LDI was performed on two separate occasions following the onset of daily exercise. During the immediate 15 min postexercise evaluation, LDI scanning was obtained in quadruplicate, to allow identification of peak flux ratios. Statistical analysis included unpaired t-tests and analysis of variance. RESULTS: After FAL, the LDI flux ratio reached a nadir between days 1 and 2, then stabilized by day 14 and remained stable through day 25. The clinical ischemic score stabilized at day 7 and remained stable throughout the rest of the experiment. Based on stabilization of both the clinical ischemic score and LDI ratio, exercise training began on day 15. The peak 15 min postexercise LDI ratio increased significantly compared to the preexercise ratio on day 17 (0.48 +/- 0.04 vs. 0.34 +/- 0.04, p < 0.05) and day 25 (0.37 +/- 0.03 vs. 0.27 +/- 0.03, p < 0.01). Within 2 hr of exercise, the LDI ratio returned to preexercise levels on both days 17 and 25. CONCLUSION: Clinical and hemodynamic stabilization of limb perfusion is evident by 14 days after FAL. FAL followed by demand ischemia results in a reversible relative hyperemic response similar to that observed in exercising human claudicants. A murine model of FAL associated with demand ischemia may be useful to evaluate the metabolic, inflammatory, and flow-related changes associated with claudication in humans.

Development and implementation of endovascular capabilities in wartime.

BACKGROUND: Endovascular techniques are widespread in the management of civilian trauma and provide standard treatment for select injuries. Despite the commonality of this less invasive technology, there have been no reports on its use in wartime. The objective of this study was to describe the implementation of endovascular capability at a level III surgical facility in Iraq and illustrate the effectiveness of catheter-based techniques. METHODS: From September 1, 2004 through April 30, 2007, injuries at the Air Force Theater Hospital, Balad, Iraq, were registered in a database and reviewed. Patients in whom endovascular procedures were performed comprise the study group (N = 139). RESULTS: During this period, 150 catheter-based procedures were performed, including placement of 39 vena cava filters. The 111 nonfilter procedures were performed in the setting of extremity (N = 72), cervical (N = 19), and torso (N = 20) injuries. Of the diagnostic procedures, an abnormal finding was present in 67 (61%) cases, and 47 of these underwent either open surgical repair (N = 30) or endovascular treatment (N = 17). Endovascular therapies fell into three categories: embolization (N = 10), covered stent placement (N = 5), or miscellaneous (N = 2). The technical success rate of endovascular treatments was 100%, and procedure-related complications were uncommon (N = 4; 3%). CONCLUSION: This report is the first to demonstrate the effectiveness of diagnostic and therapeutic endovascular capability in the management of acute wartime injury. Implementation of this capability has unique requirements related to imaging and a trauma-specific endovascular inventory. Once established, however, endovascular capability markedly expands the injury management armamentarium and, in certain cases, provides the preferred treatment.

In-theater management of vascular injury: 2 years of the Balad Vascular Registry.

BACKGROUND: Wartime vascular injury management has traditionally advanced vascular surgery. Despite past military experience, and recent civilian publications, there are no reports detailing current in-theater treatment. The objective of this analysis is to describe the management of vascular injury at the central echelon III surgical facility in Iraq, and to place this experience in perspective with past conflicts. STUDY DESIGN: Vascular injuries evaluated at our facility between September 1, 2004 and August 31, 2006 were prospectively entered into a registry and reviewed. RESULTS: During this 24-month period, 6,801 battle-related casualties were assessed. Three hundred twenty-four (4.8%) were diagnosed with 347 vascular injuries. Extremity injuries accounted for 260 (74.9%). Vascular injuries in the neck (n = 56; 16.1%) and thoracoabdominal domain (n = 31; 8.9%) were less common. US forces accounted for 149 casualties (46%), 97 (30%) were local civilian, and 78 (24%) were Iraqi forces. One hundred seven (33%) patients with vascular injury were evacuated from forward locations after treatment initiation. Fifty-four (50%) of these had temporary shunts placed. Of 43 proximal shunts placed in-field, 37 (86%) were patent at the time of our assessment. Early amputation rate was 6.6% for those extremity injuries treated for limb salvage. Perioperative mortality was 4.3%. CONCLUSIONS: This evaluation represents the first in-theater report of wartime vascular injury since Vietnam. Extremity injuries continue to predominate, although the incidence of vascular injury appears to be somewhat increased. Local forces and civilians now represent a substantial proportion of those injured. The principles of rapid evacuation, temporary shunting, and early reconstruction are effective, with satisfactory early in-theater limb salvage.

Meckel's diverticulitis: a rare etiology of an acute abdomen during pregnancy.

Perforated Meckel's diverticulum (MD) is a rare complication of pregnancy. Its diagnosis, however, must be considered in all cases of intra-abdominal disease, as its presentation is similar to appendicitis. Prompt diagnosis and appropriate treatment is imperative in these cases due to the high rate of perforation leading to fetal and maternal morbidity and mortality. The usual lesion affecting a patient with MD and a review of the literature on other unusual causes of an acute abdomen in pregnancy is presented in the following report.

Management of blunt peripheral arterial injury.

The recognition of blunt vascular injury has increased in recent years due to an improved understanding of blunt mechanical forces, mechanisms of injury, and awareness that such injuries are often occult. This has been aided by improved quality and expanded availability of noninvasive studies. As a result, outcomes following blunt vascular injury have improved. Compared to penetrating vascular injury and other vascular disease processes, blunt vascular injury has unique features that make it useful to consider as a distinct clinical entity. Manifestations of blunt vascular injury may develop in a delayed fashion and present with more subtle findings, such as a pulse deficit or diminished ankle-brachial pressure index. The objective of this review is to present a brief historical perspective on blunt vascular injury as well as an appraisal of current diagnostic and treatment strategies. Blunt vascular injury will be discussed in distinct anatomic regions, including cervical and upper and lower extremity and evidence-based management strategies developed.

Echelons of care and the management of wartime vascular injury: a report from the 332nd EMDG/Air Force Theater Hospital, Balad Air Base, Iraq.

The objective of this report is to provide a contemporary in-theater account on the systematic management of wartime vascular injury. Included are strategies at each echelon of care that affect the treatment of these injuries. In addition, the aim of this report is to present a modern wartime vascular registry describing rates and distribution of injury in what is now a mature military conflict. A 15-month review (September 1, 2004 through December 1, 2005) from the central level III echelon facility in Iraq (332nd EMDG/Air Force Theater Hospital) presented by the in-theater Consultants for Vascular Surgery. During this period 13 460 casualties were treated at or evacuated through our location, 3096 (23%) with battle-related injuries. Vascular injuries comprised 6.6% (N = 209) of battle-related trauma in the following distribution: extremity 79% (n = 166), neck 13% (n = 27), thoracoabdominal 8% (n = 16). Three levels (formerly echelons) of care are active in theater each with strategies that affect vascular injury management: Level 1: use of commercial tourniquets; level 2: use of temporary vascular shunts as damage control adjuncts; and level 3: definitive repair of arterial and venous injuries in theater using autologous vein. Evacuation patterns and the position of the Air Force Theater Hospital have allowed the formation of a contemporary wartime vascular registry. The rate of vascular injury appears increased compared to that of Vietnam with extremity injuries most prevalent. Effective strategies are in place at each of 3 levels of care that affect the management of vascular injury.

Methylene blue enteric mapping for intraoperative localization in obscure small bowel hemorrhage: report of a new technique and literature review: combined intraoperative methylene blue mapping and enterectomy.

BACKGROUND: Small bowel sources of obscure gastrointestinal bleeding present both a diagnostic and therapeutic challenge. Due to the normal external appearance of the vast majority of small bowel lesions that cause obscure gastrointestinal bleeding, multiple methods of intraoperative localization have been reported. When an arteriographic abnormality is found, the use of vital dye enteric mapping is one of the most effective localization techniques. CASE REPORT: We present a new technique combining superselective mesenteric angiography with methylene blue enteric mapping and small bowel resection performed during the same operative procedure. This technique was successfully applied in a patient with a jejunal arteriovenous malformation. Included is a review of methods of intraoperative localization with a focus on vital dye staining-guided enterectomy.

Vascular injuries in the young.

Vascular injuries in children result from invasive procedures, penetrating trauma, and blunt injuries. Depending on local practice patterns, these injuries are managed by a range of subspecialists with little guidance from the literature on the optimal approach to diagnosis and management of these challenging injuries. Recently, more aggressive operative approaches to managing injuries in the young have been advocated and have been supported by recent reports from several series of wartime vascular injuries involving children. This review summarizes the scope of both iatrogenic and traumatic vascular injuries and the historic and current literature on these topics. Treatment strategies are also reviewed placing emphasis on the transition from ligation or heparinization to the current trend of managing suspected vascular injuries with operative exploration and repair, including, in some instances, endovascular diagnosis and intervention. Future directions for clinical research in this area are also discussed, which will hopefully promote more multidisciplinary collaboration in this area.

Penetrating femoropopliteal injury during modern warfare: experience of the Balad Vascular Registry.

OBJECTIVE: Wounding patterns, methods of repair, and outcomes from femoropopliteal injury have been documented in recent civilian literature. In Operation Iraqi Freedom, as in past conflicts, these injuries continue to be a therapeutic challenge. Therefore, the objective of the current study is to document the pattern of femoropopliteal injuries, methods of repair, and early outcomes during the current military campaign in Iraq. METHODS: From September 1, 2004, to April 30, 2007, all vascular injuries arriving at the Air Force Theater Hospital (the central echelon III medical facility in Iraq; equivalent to a civilian level I trauma center), Balad Air Base, Iraq were prospectively entered into a registry. From this, injuries involving the lower extremities were reviewed. RESULTS: During the 32-month study period, 9289 battle-related casualties were assessed. Of these, 488 (5.3%) were diagnosed with 513 vascular injuries, and 142 casualties sustained 145 injuries in the femoropopliteal domain. Femoral level injury was present in 100, and popliteal level injury occurred in 45. Injuries consisted of 59 isolated arterial, 11 isolated venous, and 75 combined. Fifty-eight casualties were evacuated from forward locations. Temporary arterial shunts were placed in 43, of which 40 (93%) were patent on arrival at our facility. Our group used shunts for early reperfusion before orthopedic fixation, during mass casualty care, or autogenous vein harvest in 11 cases. Arterial repair was accomplished with autogenous vein in 118 (88%), primary means in nine (7%), or ligation in seven (5%). Venous injury was repaired in 62 (72%). Associated fracture was present in 55 (38%), and nerve injury was noted in 19 (13%). Early limb loss due to femoropopliteal penetrating injury occurred in 10 (6.9%). Early mortality was 3.5% (n = 5). CONCLUSIONS: Femoropopliteal vascular injury remains a significant reality in modern warfare. Femoral injuries appear more prevalent than those in the popliteal region. Early results of in-theater repair are comparable with contemporary civilian reports and are improved from the Vietnam era. Rapid evacuation and damage control maneuvers such as temporary shunting and early fasciotomy assist timely definitive repair and appear effective.

The complete management of extremity vascular injury in a local population: a wartime report from the 332nd Expeditionary Medical Group/Air Force Theater Hospital, Balad Air Base, Iraq.

BACKGROUND: Although the management of vascular injury in coalition forces during Operation Iraqi Freedom has been described, there are no reports on the in-theater treatment of wartime vascular injury in the local population. This study reports the complete management of extremity vascular injury in a local wartime population and illustrates the unique aspects of this cohort and management strategy. METHODS: From September 1, 2004, to August 31, 2006, all vascular injuries treated at the Air Force Theater Hospital (AFTH) in Balad, Iraq, were registered. Those in noncoalition troops were identified and retrospectively reviewed. RESULTS: During the study period, 192 major vascular injuries were treated in the local population in the following distribution: extremity 70% (n=134), neck and great vessel 17% (n=33), and thoracoabdominal 13% (n=25). For the extremity cohort, the age range was 4 to 68 years and included 12 pediatric injuries. Autologous vein was the conduit of choice for these vascular reconstructions. A strict wound management strategy providing repeat operative washout and application of the closed negative pressure adjunct was used. Delayed primary closure or secondary coverage with a split-thickness skin graft was required in 57% of extremity wounds. All patients in this cohort remained at the theater hospital through definitive wound healing, with an average length of stay of 15 days (median 11 days). Patients required an average of 3.3 operations (median 3) from the initial injury to definitive wound closure. Major complications in extremity vascular patients, including mortality, were present in 15.7% (n=21). Surgical wound infection occurred in 3.7% (n=5), and acute anastomotic disruption in 3% (n=4). Graft thrombosis occurred in 4.5% (n=6), and early amputation and mortality rates during the study period were 3.0% (n=4) and 1.5% (n=2), respectively. CONCLUSIONS: To our knowledge, this study represents the first large report of wartime extremity vascular injury management in a local population. These injuries present unique challenges related to complex wounds that require their complete management to occur in-theater. Vascular reconstruction using vein, combined with a strict wound management strategy, results in successful limb salvage with remarkably low infection, amputation and mortality rates.

The use of temporary vascular shunts as a damage control adjunct in the management of wartime vascular injury.

BACKGROUND: While the use of vascular shunts as a damage control adjunct has been described in series from civilian institutions no contemporary military experience has been reported. The objective of this study is to examine patterns of use and effectiveness of temporary vascular shunts in the contemporary management of wartime vascular injury. MATERIALS: From September 1, 2004 to August 31, 2005, 2,473 combat injuries were treated at the central echelon III surgical facility in Iraq. Vascular injuries were entered into a registry and reviewed. Location of shunts was divided into proximal and distal, and shunt patency, complications and limb viability were examined. RESULTS: There were 126 extremity vascular injuries treated. Fifty-three (42%) had been operated on at forward locations and 30 of 53 (57%) had temporary shunts in place upon arrival to our facility. The patency for shunts in proximal vascular injuries was 86% (n = 22) compared with 12% (n = 8) for distal shunts (p < 0.05). All shunts placed in proximal venous injuries were patent (n = 4). Systemic heparin was not used and there were no shunt complications. All shunted injuries were reconstructed with vein in theater and early viability for extremities in which shunts were used was 92%. CONCLUSIONS: Temporary vascular shunts are common in the management of wartime vascular injury. Shunts in proximal injuries including veins have high patency rates compared with those placed in distal injuries. This vascular adjunct represents a safe and effective damage control technique and is preferable to attempted reconstruction in austere conditions.

Upper extremity vascular injury: a current in-theater wartime report from Operation Iraqi Freedom.

Past wartime experience and recent civilian reports indicate upper extremity (UE) vascular injury occurs less often and with less limb loss than lower extremity (LE) injury. Given advances in critical care, damage control techniques, and military armor technology, the objective of this evaluation was to define contemporary patterns of UE injury and effectiveness of vascular surgical management in UE vascular injury during Operation Iraqi Freedom (OIF). From 1 September 2004 through 31 August 2005, 2,473 combat-related injuries were treated at the central echelon III surgical facility in Iraq. Patients with UE vascular injuries upon arrival were reviewed. Vessels injured were delineated. Therapeutic interventions, early limb viability, and complication rates following vascular repair were recorded. Of casualties treated during the study period, 43 (1.7%) UE and 83 (3.3%) LE vascular injuries were identified. Of the UE injuries, 11 (26%) had been operated on at forward locations and six (14%) had temporary shunts in place upon arrival at our facility. Injury levels included 10 (23%) subclavian-axillary, 25 (58%) brachial, and 10 (23%) distal to the brachial bifurcation. Two patients had multilevel injury. Twenty-eight grafts were placed, and 10 vessel repairs and eight ligations were performed. Two (4.7%) brachial interposition grafts required removal due to infection. Four (9.3%) subacute brachial graft thromboses occurred. Four (9.3%) patients underwent early UE amputation. In this most recent U.S. military evaluation of wartime UE vascular injury, UE injury appears rare, with LE injury twice as frequent. Yet, UE limb loss appears more substantial than noted previously. These findings are likely related to significant tissue destruction occurring with the combined mechanisms of injury sustained in OIF.