Jonathan L. Eliason

Current concepts in the pathogenesis of abdominal aortic aneurysm

Abdominal aortic aneurysms (AAAs) are a significant medical problem with a high mortality. The primary diagnostic code for AAA accounts for approximately 150,000 inpatient hospital admissions per year. The most recent published data from the National Vital Statistics Report on Deaths from the year 2000 show that AAAs and aortic dissection composed the tenth leading cause of death in white men 65 to 74 years old and accounted for nearly 16,000 deaths overall. The year 2000 National Hospital Discharge Summary reports more than 30,000 open operations for repair of AAAs in the United States. Understanding the cause of AAAs therefore becomes an important undertaking. The pathogenesis of AAAs is complex and multifactorial. Histologically, AAAs are characterized by destruction of elastin and collagen in the media and adventitia, smooth muscle cell loss with thinning of the medial wall, infiltration of lymphocytes and macrophages, and neovascularization. Inflammation is a common underlying feature of both aneurysm disease and atherosclerosis. However, atherosclerosis is primarily found within the intima and media, whereas aneurysm disease typically affects the media and adventitia. A National Heart, Lung and Blood Institute Request for Applications (HL-99-007) entitled “Pathogenesis of Abdominal Aortic Aneurysms” identified four mechanisms relevant to AAA formation: proteolytic degradation of aortic wall connective tissue, inflammation and immune responses, biomechanical wall stress, and molecular genetics. PROTEOLYTIC DEGRADATION OF AORTIC WALL CONNECTIVE TISSUE

Resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct for hemorrhagic shock.

Temporary occlusion of the aorta as an operative method to increase proximal or central perfusion to the heart and brain in the setting of shock is not new.1 Resuscitative aortic occlusion with a balloon was reported as early as the Korean War and has been described in more recent publications.2–5 Despite potential advantages over thoracotomy with aortic clamping, resuscitative endovascular balloon occlusion of the aorta (REBOA) for trauma has not been widely adopted. Broader application of this procedure may have lagged because of latent technology, a poorly understood skill set, or anticipated ineffectiveness of the technique. However, the recent evolution of endovascular technology and its clear benefit in managing vascular disease such as ruptured abdominal aortic aneurysm suggest that a reappraisal of this technique for trauma is needed. The objective of this report is to provide a technical description of REBOA. To simplify, this maneuver can be considered in the following five steps each with specific procedural considerations (Table 1):

Neutrophil Depletion Inhibits Experimental Abdominal Aortic Aneurysm Formation

Background—Neutrophils may be an important source of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two matrix-degrading enzymes thought to be critical in the formation of an abdominal aortic aneurysm (AAA). The purpose of this investigation was to test the hypothesis that neutrophil depletion would limit experimental AAA formation by altering one or both of these enzymes. Methods and Results—Control, rabbit serum–treated (RS; n=27) or anti-neutrophil-antibody–treated (anti-PMN; n=25) C57BL/6 mice underwent aortic elastase perfusion to induce experimental aneurysms. Anti-PMN–treated mice became neutropenic (mean, 349 cells/&mgr;L), experiencing an 84% decrease in the circulating absolute neutrophil count (P<0.001) before elastase perfusion. Fourteen days after elastase perfusion, control mice exhibited a mean aortic diameter (AD) increase of 104±14% (P<0.0001), and 67% developed AAAs, whereas anti-PMN–treated mice exhibited a mean AD increase of 42±33%, with 8% developing AAAs. The control group also had increased tissue neutrophils (20.3 versus 8.6 cells per 5 high-powered fields [HPFs]; P=0.02) and macrophages (6.1 versus 2.1 cells per 5 HPFs, P=0.005) as compared with anti-PMN–treated mice. There were no differences in monocyte chemotactic protein-1 or macrophage inflammatory protein-1&agr; chemokine levels between groups by enzyme-linked immunosorbent assay. Neutrophil collagenase (MMP-8) expression was detected only in the 14-day control mice, with increased MMP-8 protein levels by Western blotting (P=0.017), and MMP-8–positive neutrophils were seen almost exclusively in this group. Conversely, there were no statistical differences in MMP-2 or MMP-9 mRNA expression, protein levels, enzyme activity, or immunostaining patterns between groups. When C57BL/6 wild-type (n=15) and MMP-8–deficient mice (n=17) were subjected to elastase perfusion, however, ADs at 14 days were no different in size (134±7.9% versus 154±9.9%; P=0.603), which suggests that MMP-8 serves only as a marker for the presence of neutrophils and is not critical for AAA formation. Conclusions—Circulating neutrophils are an important initial component of experimental AAA formation. Neutrophil depletion inhibits AAA development through a non–MMP-2/9–mediated mechanism associated with attenuated inflammatory cell recruitment.

Frailty, core muscle size, and mortality in patients undergoing open abdominal aortic aneurysm repair

OBJECTIVES Determining operative risk in patients undergoing aortic surgery is a difficult process, as multiple variables converge to affect overall mortality. Patient frailty is certainly a contributing factor, but is difficult to measure, with surgeons often relying on subjective or intuitive influences. We sought to use core muscle size as an objective measure of frailty, and determine its utility as a predictor of survival after abdominal aortic aneurysm (AAA) repair. METHODS Four hundred seventy-nine patients underwent elective open AAA repair between 2000 and 2008. Two hundred sixty-two patients (54.7%) had preoperative computed tomography (CT) scans available for analysis. Cross-sectional areas of the psoas muscles at the level of the L4 vertebra were measured. The covariate-adjusted effect of psoas area on postoperative mortality was assessed using Cox regression. RESULTS Of the 262 patients, there were 55 deaths and the mean length of follow-up was 2.3 years. Cox regression revealed a significant association between psoas area and postoperative mortality (P = .003). The effect of psoas area was found to decrease significantly as follow-up time increased (P = .008). Among all covariates included in the Cox models (including predictors of mortality such as American Society of Anesthesiologists [ASA] score), the psoas area was the most significant. CONCLUSION Core muscle size, an objective measure of frailty, correlates strongly with mortality after elective AAA repair. A better understanding of the role of frailty and core muscle size may aid in risk stratification and impact timing of surgical repair, especially in more complex aortic operations.

Gender Differences in Experimental Aortic Aneurysm Formation

Objective—It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs). Methods and Results—Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase. Conclusions—These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.

A National and Single Institutional Experience in the Contemporary Treatment of Acute Lower Extremity Ischemia

Objective To determine the contemporary clinical relevance of acute lower extremity ischemia and the factors associated with amputation and in-hospital mortality. Summary Background Data Acute lower extremity ischemia is considered limb- and life-threatening and usually requires therapy within 24 hours. The equivalency of thrombolytic therapy and surgery for the treatment of subacute limb ischemia up to 14 days duration is accepted fact. However, little information exists with regards to the long-term clinical course and therapeutic outcomes in these patients. Methods Two databases formed the basis for this study. The first was the National Inpatient Sample (NIS) from 1992 to 2000 of all patients (N = 23,268) with a primary discharge diagnosis of acute embolism and thrombosis of the lower extremities. The second was a retrospective University of Michigan experience from 1995 to 2002 of matched ICD-9-CM coded patients (N = 105). Demographic factors, atherosclerotic risk factors, the need for amputation, and in-hospital mortality were assessed by univariate and multivariate logistic regression analysis. Results In the NIS, the mean patient age was 71 years, and 54% were female. The average length of stay (LOS) was 9.4 days, and inflation-adjusted cost per admission was

A novel fluoroscopy-free, resuscitative endovascular aortic balloon occlusion system in a model of hemorrhagic shock.

25,916. The amputation rate was 12.7%, and mortality was 9%. Decreased amputation rates accompanied: female sex (0.90, 0.81–0.99), age less than 63 years (0.47, 0.41–0.54), angioplasty (0.46, 0.38–0.55), and embolectomy (0.39, 0.35–0.44). Decreased mortality accompanied: angioplasty (0.79, 0.64–0.96), heparin administration (0.50, 0.29–0.86), and age less than 63 years(0.27, 0.23–0.33). The University of Michigan patients’ mean age was 62 years, and 57% were men. The LOS was 11 days, with a 14% amputation rate and a mortality of 12%. Prior vascular bypasses existed in 23% of patients, and heparin use was documented in 16%. Embolectomy was associated with decreased amputation rates (0.054, 0.01–0.27) and mortality (0.07, 0.01–0.57). Conclusions In patients with acute limb ischemia, the more widespread use of heparin anticoagulation and, in select patients, performance of embolectomy rather than pursuing thrombolysis may improve patient outcomes.

Abdominal aortic coarctation: surgical treatment of 53 patients with a thoracoabdominal bypass, patch aortoplasty, or interposition aortoaortic graft.

BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially lifesaving maneuver in the setting of hemorrhagic shock. However, emergent use of REBOA is limited by existing technology, which requires large sheath arterial access and fluoroscopy-guided balloon positioning. The objectives of this study were to describe a new, fluoroscopy-free REBOA system and to compare its efficacy to existing technology. An additional objective was to characterize the survivability of 60 minutes of REBOA using these systems in a model of hemorrhagic shock. METHODS Swine (70–88 kg) in shock underwent 60 minutes of REBOA using either a self-centering, one component prototype balloon system (PBS, n = 8) inserted (8 Fr) and inflated without fluoroscopy or a two-component, commercially available balloon system (CBS, n = 8) inserted (14 Fr) with fluoroscopic guidance. Following REBOA, resuscitation occurred for 48 hours with blood, crystalloid, and vasopressors. End points included accurate balloon positioning, hemodynamics, markers of ischemia, resuscitation requirements, and mortality. RESULTS Posthemorrhage mean arterial pressure (mm Hg) was similar in the CBS and PBS groups (35 [8] vs. 34 [5]; p = 0.89). Accurate balloon positioning and inflation occurred in 100% of the CBS and 88% of the PBS group. Following REBOA, mean arterial pressure increased comparably in the CBS and PBS groups (81 [20] vs. 89 [16]; p = 0.21). Lactate peaked in the CBS and PBS groups (10.8 [1.4] mmol/L vs. 13.2 [2.1] mmol/L; p = 0.01) 45 minutes following balloon deflation but returned to baseline by 24 hours. Mortality was similar between the CBS and PBS groups (12% vs. 25%, p = 0.50). CONCLUSION This study reports the feasibility and efficacy of a novel, fluoroscopy-free REBOA system in a model of shock. Despite a significant physiologic insult, 60 minutes of REBOA is tolerated and recoverable. Development of lower profile, fluoroscopy-free endovascular balloon occlusion catheters may allow proactive aortic control in patients at risk for hemorrhagic shock and cardiovascular collapse.

A systematic review of the use of resuscitative endovascular balloon occlusion of the aorta in the management of hemorrhagic shock.

OBJECTIVE Abdominal aortic coarctation is uncommon and often complicated with coexisting splanchnic and renal artery occlusive disease. This study was undertaken to define the clinical and anatomic characteristics of this entity, as well as the technical issues and outcomes of its operative treatment. METHODS Fifty-three patients, 34 males and 19 females, underwent surgical treatment of abdominal aortic coarctations from 1963-2008 at the University of Michigan. Patient ages in years ranged from 2-4 (n = 4), 5-8 (n = 17), 9-14 (n = 16), 15-20 (n = 11) and 25-49 (n = 5). The mean age was 11.9 years. Developmental disease (n = 48), inflammatory aortitis (n = 4), and iatrogenic trauma (n = 1) were suspected etiologies. Aortic coarctations were suprarenal (n = 37), intrarenal (n = 12), or infrarenal (n = 4). Patients often had coexisting occlusive disease of the splanchnic (n = 33) and renal (n = 46) arteries. RESULTS Major clinical manifestations included: aortic and renal artery-related secondary hypertension (n = 50), symptomatic lower extremity ischemia (n = 3), and intestinal angina (n = 3). Primary aortic reconstructive procedures included: thoracoabdominal bypass (n = 26), patch aortoplasty (n = 24), or an aortoaortic interposition graft (n = 3). Primary splanchnic (n = 19) or renal (n = 47) arterial reconstructions were performed as simultaneous (n = 45) or staged (n = 13) procedures in relation to the aortic surgery. Benefits existed regarding improved control of hypertension (n = 46), as well as elimination of extremity ischemia (n = 3) and mesenteric angina (n = 3). Secondary renal or splanchnic arterial reoperations (n = 8) were performed without mortality 5 days to 12 years postoperative for failed primary procedures. Secondary aortic procedures, 5 to 14 years postoperative, were performed for patch aortoplasties that became stenotic (n = 2) or aneurysmal (n = 1), and when thoracoabdominal bypasses developed an anastomotic narrowing (n = 1) or proved inadequate in size with patient growth (n = 1). No perioperative mortality accompanied either the primary or secondary aortic reconstructive procedures. CONCLUSION Abdominal aortic coarctation represents a complex vascular disease. Individualized treatment changed little over the period of study, remaining dependent on the pattern of anatomic lesions, patient age, and anticipated growth potential. This experience documented salutary outcomes exceeding 90% following carefully performed operative therapy.

Hybrid debranching with endovascular repair for thoracoabdominal aneurysms: a comparison with open repair.

BACKGROUND Torso hemorrhage remains a leading cause of potentially preventable death within trauma, acute care, vascular, and obstetric practice. A proportion of patients exsanguinate before hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive hemostasis. A systematic review was conducted to characterize the current clinical use of REBOA and its effect on hemodynamic profile and mortality. METHODS A systematic review (1946–2015) was conducted using EMBASE and MEDLINE. Original studies on human subjects, published in English language journals, were considered. Articles were included if they reported data on hemodynamic profile and mortality. RESULTS A total of 83 studies were identified; 41 met criteria for inclusion. Clinical settings included postpartum hemorrhage (5), upper gastrointestinal bleeding (3), pelvic surgery (8), trauma (15), and ruptured aortic aneurysm (10). Of the 857 patients, overall mortality was 423 (49.4%); shock was evident in 643 (75.0%). Pooled analysis demonstrated an increase in mean systolic pressure by 53 mm Hg (95% confidence interval, 44–61 mm Hg) following REBOA use. Data exhibited moderate heterogeneity with an I2 of 35.5. CONCLUSION REBOA has been used in a variety of clinical settings to successfully elevate central blood pressure in the setting of shock. Overall, the evidence base is weak with no clear reduction in hemorrhage-related mortality demonstrated. Formal, prospective study is warranted to clarify the role of this adjunct in torso hemorrhage. LEVEL OF EVIDENCE Systematic review, level IV.