Arrest of progression of pre-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice by low level laser phototherapy.

BACKGROUND AND OBJECTIVES: Using non-invasive, high-frequency ultrasonography (HF-u/s), we showed that low-level laser phototherapy (LLL) inhibits de-novo formation of abdominal aortic aneurysms (AAA) in apolipoprotein-E-deficient (Apo-E(-/-)) mice. The current study tests the effect of LLL on the progression of pre-induced AAA. STUDY DESIGN/MATERIAL AND METHODS: AAA was induced in Apo-E(-/-) mice (age 16-20 weeks) by subcutaneous infusion of angiotensin-II using osmotic minipumps (1000 ng/kg/minutes, 4 weeks). HF-u/s (40 MHz, 0.01 mm resolution, Vevo-770, VisualSonics) was used to measure the maximum cross-sectional-diameter (MCD) of the suprarenal abdominal aorta, the anterior wall displacement (AWD), and radial wall velocity (RWV). The aortas of mice that developed >35% dilatation at 2 weeks over baseline were exposed retroperitoneally and treated with LLL (780 nm, 2.2 J/cm(2), 9 minutes) or sham-operated. HF-u/s was repeated at 4 weeks, the mice sacrificed by perfusion fixation, and the aortas excised for histopathology. RESULTS: Of all mice with >35% MCD expansion of the suprarenal aorta at 2 weeks, 7(58%) of 12 non-treated, but only 1(7%) of 14 LLL, had increased MCD(> 1 SD) at 4 weeks (P < 0.009 by Fisher's Exact Test [FET]). The mean change in MCD from 2-4 weeks was also markedly reduced in the LLL-treated mice (control vs. LLL, 0.24 ± 0.25 vs. -0.06 ± 0.39 mm, P = 0.029 by unpaired t-test). Similar results were obtained when limiting the analysis to animals with ≥ 50% expansion at 2 weeks. The deterioration in AWD from 2-4 weeks in non-treated controls was not observed in LLL-treated animals (ΔAWD: control, 0.03 ± 0.05 mm, P < 0.036 vs. LLL, 0.00 ± 0.05, P = 0.91 by paired t-test). By the modified Daugherty classification, we found significantly fewer severe aneurysms at 4 weeks in the LLL-treated animals versus control (3 of 10 vs. 9 of 11, P = 0.03 by FET). CONCLUSIONS: LLL not only prevents de novo development of AAA, but, from this study, also arrests further progression of pre-induced AAA and its associated deterioration in the biomechanical integrity of the aortic wall in Apo-E(-/-) mice.

Inadequate reinforcement of transmedial disruptions at branch points subtends aortic aneurysm formation in apolipoprotein-E-deficient mice.

INTRODUCTION: Infusion of angiotensin-II (Ang-II) in apolipoprotein-E-deficient mice (Apo-E(-/-)) results in suprarenal abdominal aortic aneurysm (AAA) in 30-85% of cases. This study identifies the apparent mechanism by which some animals do, but others do not, develop AAA in this model. METHODS: Male Apo-E(-/-) mice were infused with Ang-II (n=21) or saline (n=6) and sacrificed at 4 weeks. Aortas were excised, embedded in paraffin, sectioned (250 µm intervals), and stained. Sites of transmedial disruption (TMD) were identified and characterized, and their relationship to the 4 major aortic side branches (celiac, superior mesenteric, and renals) were determined. RESULTS: The frequency of TMDs in Ang-II-infused mice that formed AAA (n=9) was similar to those that did not (n=12) (AAA vs. no-AAA: 25 of 36[69%] vs. 28 of 48[58%] branches, P=.3 by chi-square). All TMDs were at branch points. However, in animals with AAA, the mean maximum length of the TMDs was significantly larger (1.94±1.6 vs. 0.65±0.5mm, P=.007 by Mann Whitney U test), the #mac-2(+) macrophages per 0.01mm(2) of defect area was greater (32±10 vs. 19±11, P<.02 by Kruskal-Wallis with Conover-Inman post hoc), the % area of attempted repair occupied by collagen was less (17±13% vs. 44±15%, P=.0009 by Mann Whitney U test), and the density of collagen per unit length of media missing was also markedly less (0.13±0.2 vs. 1.14±1.0, P=.0001 by Mann Whitney U test). CONCLUSIONS: Reinforcement of transmedial defects at branch points by wall matrix is a key intrinsic player in limiting AAA formation in the Ang-II-infused, Apo E(-/-) mouse and a potentially important mechanism-based therapeutic target for management of small, slowly progressing aneurysms.

Lessons from Animal Models of Arterial Aneurysm.

We review the results from the most common animal models of arterial aneurysm, including recent findings from our novel, laparoscopy-based pig model of abdominal aortic aneurysm, that contribute important insights into early pathogenesis. We emphasize the relevance of these findings for evaluation of treatment protocols and novel device prototypes for mechanism-based prevention of progression and rupture.

Low level laser arrests abdominal aortic aneurysm by collagen matrix reinforcement in apolipoprotein E-deficient mice.

BACKGROUND AND OBJECTIVES: Recent in vitro studies by our group indicated that low level laser irradiation (LLLI) modifies cellular processes essential to the progression of abdominal aortic aneurysm (AAA). Using high-frequency ultrasonography (HF-u/s) in the angiotensin-II (Ang-II)-infused, apolipoprotein-E-deficient (Apo-E(-/-) ) mouse model of AAA, we found that LLLI markedly inhibited aneurysm formation and preserved arterial wall elasticity. We now report, using quantitative histopathology, the likely mechanism underlying the preventative effect of LLLI on aneurysm formation in this model. STUDY DESIGN/MATERIALS AND METHODS: This study was performed on 32 Apo-E(-/-) mice of which 10 were Ang-II-infused and LLL-irradiated (780 nm, 2 J/cm(2) , 9-minutes), 12 were Ang-II-infused but not irradiated, and 10 were saline infused. The aortas were excised at 28d, sectioned at 250 µm intervals, and stained with H + E, Movat-pentachrome and picrosirius-red for histomorphometry, and immunostained with Mac-2 and α-actin for detection of macrophages and SMCs, respectively. RESULTS: Transmural disruptions of the aorta occurred with distinct predilection for branch orifices. In the LLLI-treated animals, the frequency of these disruptions was lower (#branches with break points: 17 of 40 vs. 32 of 48, P = 0.023 by Chi-squared), their size smaller (length [mm]: 0.48 ± 0.26 vs. 0.98 ± 1.42, P = 0.044 by ANOVA with FPLSD), and the number of Mac-2-positive macrophages in the intramural areas of these disruptions lower than in the non-treated control (#Macrophages/0.01 mm(2) at break points: 11.6 ± 7.2 vs. 26.0 ± 15.7, P = 0.016 by Kruskal-Wallis). The average size of the medial SMCs was larger reflecting a heightened synthetic state (SMC size [µm(2) ]: 463.9 ± 61.4 vs. 354.9 ± 71.7, P = 0.001 by ANOVA with FPLSD). Furthermore, at sites of transmural disruption, the %area occupied by collagen of the overall area of attempted repair (%Col/WO) was significantly greater in the LLLI-treated animals versus control (%Col/WO: 41 ± 13 vs. 32 ± 16, P = 0.009 by ANOVA with FPLSD). CONCLUSION: Enhanced matrix reinforcement and modification of the inflammatory response at sites of transmural injury are prominent mechanisms by which LLLI reduces AAA progression in this model.

Low-level laser irradiation inhibits abdominal aortic aneurysm progression in apolipoprotein E-deficient mice.

AIMS: Increased early detection of abdominal aortic aneurysm (AAA) and the severe complications of its current treatment have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. Recent in vitro studies from our laboratory have shown that low-level laser irradiation (LLLI) (780 nm) modifies cellular processes fundamental to aneurysm progression. The present study was designed to determine whether LLLI retards the progression of suprarenal AAA in vivo. METHODS AND RESULTS: High-frequency ultrasonography (0.01 mm resolution) was used to quantify the effect of LLLI on aneurysmatic aortic dilatation from baseline to 4 weeks after subcutaneous infusion of angiotensin II by osmotic minipumps in the apolipoprotein E-deficient mouse. At 4 weeks, seven of 15 non-irradiated, but none of the 13 LLLI, mice had aneurysmal dilatation in the suprarenal aneurysm-prone segments that had progressed to >or=50% increase in maximal cross-sectional diameter (CSD) over baseline (P = 0.005 by Fisher's exact test). The mean CSD of the suprarenal segments (normalized individually to inter-renal control segments) was also significantly lower in irradiated animals (LLLI vs. non-irradiated: 1.32 +/- 0.14 vs. 1.82 +/- 0.39, P = 0.0002 by unpaired, two-tailed t-test) with a 94% reduction in CSD at 4 weeks compared with baseline. M-mode ultrasound data showed that reduced radial wall velocity seen in non-treated was significantly attenuated in the LLLI mice, suggesting a substantial effect on arterial wall elasticity. CONCLUSION: These in vivo studies, together with previous in vitro studies from this laboratory, appear to provide strong evidence in support of a role for LLLI in the attenuation of aneurysm progression. Further studies in large animals would appear to be the next step towards testing the applicability of this technology to the human interventional setting.

Urgent endovascular stent-graft placement for traumatic penetrating subclavian artery injuries.

Penetrating injuries may infrequently cause pseudoaneurysms, lacerations and arteriovenous fistulas involving the subclavian artery. These injuries present with life-threatening bleedings, associated regional injuries and critical limb ischemia and although surgery has been considered the treatment of choice, subclavian injuries pose a real surgical challenge. We prospectively examined data of six patients presenting with penetrating subclavian artery injuries that were treated by urgent endovascular stent-graft placements. All stent-grafts were deployed successfully achieving complete exclusion of the pseudoaneurysm, control of bleeding and reconstruction of the injured artery. No procedural complications, stent thrombosis or stent infections occurred during hospitalization. One patient developed stenosis at 7 months, which required angioplasty. The series mean clinical and ultrasound-CTA follow-up is 38+/-19.7 months (range 11-60 months) and 28+/-19.1 months (range 6-58 months), respectively. This series shows the feasibility of endovascular repair by means of stent-grafts for selected patients with acute penetrating injuries of the subclavian arteries. This approach proved to be safe and effective in restoring the arterial lumen and patency, excluding the pseudoaneurysms and controlling the bleeding caused by subclavian lacerations. Mid-term follow-up on stent-graft patency rates are encouraging.

[Evolution of the surgical repair of thoracoabdominal aortic aneurysm].

BACKGROUND: Thoracoabdominal aortic aneurysm repair requires complex surgery. Clamping of the descending aorta during the operation results in organ malperfusion, ischemia, and in some cases, irreversible end-organ damage and death. Several methods for organ preservation during the operation evolved, resulting in decreased post-operative organ malfunction. Re-attachment of intercostal arteries, cerebrospinal fluid drainage, and temporary bypass of the clamped aorta and selective perfusion of the spinal cord, intestine, liver and kidneys are widely used during the operation. OBJECTIVES: To determine the impact of implementation of protective measures on the outcome of thoracoabdominal surgery over a decade. METHODS: Between March 1993 and March 2003, 11 patients (age 41-80 years, average 60 years) underwent thoracoabdominal aortic aneurysm repair in our hospital. Different methods for organ preservation were used during the operation. RESULTS: The early survival is 91%. One patient suffered from paraplegia and one from mild temporary paraparesis. Two patients died during the follow-up period (at 5 months from pneumonia and at 2 years from aortic arch rupture). CONCLUSIONS: Implementation of all adjuncts to protect the organs dependent on aortic perfusion may eliminate the ischemic consequences of aortic clamping.

Vascular complications of supracondylar humeral fractures in children.

The purpose of this study was to analyze the vascular complications of 24 children with supracondylar humeral fractures treated in two affiliated hospitals and to propose a management plan. Exploration and repair of the brachial artery were undertaken in 11 of the 24 cases in which the pulse did not resume following reduction of the fracture. The repaired vessels were found to be patent on follow-up. Angiography was performed in six of the 24 cases and resulted in improved management in comparison with cases in which no angiography was performed. We believe that intra-operative angiography and vascular repair are indicated in most cases in which a palpable pulse does not resume after fracture reduction.

A clinical survival score predicts the likelihood to benefit from preoperative thallium scanning and coronary revascularization before major vascular surgery.

AIMS: Guidelines advocate selective non-invasive testing before major non-cardiac surgery, yet data defining who may benefit from such tests is lacking. We aimed to find the predictors that define patients who are most likely to benefit from preoperative cardiac testing and coronary revascularization (CR). METHODS AND RESULTS: In 624 consecutive major vascular surgery patients, the preoperative thallium scanning (PTS) results and subsequent CRs were correlated with long-term (3-15 years) survival. Of all patients, 510 (80.6%) had PTS, 154 (24.7%) had moderate-severe ischaemia on PTS, and 96 (15.4%) underwent CR. Seven predictors: age >or=65, diabetes, cerebrovascular disease, ischaemic heart disease, congestive heart failure, ST-depression on preoperative ECG, and renal insufficiency, independently determined long-term survival. A long-term survival score (LTSS) comprised of these predictors, divided all patients into low, intermediate, and high-risk groups (0-1, 2-3, >or=4 predictors, respectively) with a 5-year survival of 83 +/- 2%, 60 +/- 3%, and 34 +/- 6%, respectively. Compared with low-risk patients, intermediate and high-risk patients had worse survival [HR (CI) = 2.6 (2.0-3.4) and 5.9 (4.1-8.9), respectively, P < 0.001]. Yet, only the intermediate-risk group had better long-term survival following preoperative CR [HR = 0.48 (0.31-0.75), P = 0.001]. The low-risk groups' favourable survival and high-risk groups' poor survival were not significantly affected by CR. CONCLUSION: Intermediate-risk patients (LTSS 2-3) are most likely to have a long-term survival benefit from PTS and CR.

Suicide bombing injuries: the Jerusalem experience of exceptional tissue damage posing a new challenge for the reconstructive surgeon.

BACKGROUND: Suicide bomb injuries vary in form and magnitude. From the onset of the second Palestinian "intifada" in October of 2000 until January of 2004, 577 victims of suicide bombings were admitted to the Hadassah-Hebrew University Medical Center. A single bomber carrying a handbag or belt containing multiple metal objects and explosives carried out most of the attacks. As a result, many of the victims suffered massive tissue destruction in addition to conventional blast injuries. METHODS: This article describes the management of this trauma-related "syndrome" of combined primary and high-magnitude secondary blast injury. RESULTS: The management of the extensive soft-tissue damage is described and two representative cases presented. CONCLUSION: Suicide bombing-related injuries in their present form are a true challenge for the reconstructive surgeon.

Cardiac troponin after major vascular surgery: the role of perioperative ischemia, preoperative thallium scanning, and coronary revascularization.

OBJECTIVES: We sought to determine the role of preoperative predictors, particularly ischemia, on preoperative thallium scanning (PTS) and coronary revascularization on low-level and conventional troponin elevations after major vascular surgery. BACKGROUND: Postoperative cardiac troponin (cTn) elevations have recently been shown to predict both short- and long-term mortality after vascular surgery. METHODS: The perioperative data, including PTS and subsequent coronary revascularization, continuous perioperative 12-lead ST-segment trend monitoring, cTn-I and/or cTn-T, and creatine kinase-MB fraction in the first three postoperative days, were prospectively collected in 501 consecutive elective major vascular procedures. RESULTS: Moderate to severe inducible ischemia on PTS was associated with a 49.0% incidence of low-level (cTn-I >0.6 and/or cTn-T >0.03 ng/ml) and 22.4% conventional (cTn-I >1.5 and/or cTn-T >0.1 ng/ml) troponin elevation. In contrast, patients with preoperative coronary revascularization had 23.4% and 6.4% low-level and conventional troponin elevations, respectively, similar to patients without ischemia on PTS. By multivariate logistic regression, ischemia on PTS was the most important predictor of both low-level and conventional troponin elevations (adjusted odds ratios [ORs] 2.5 and 2.7, p = 0.02 and 0.04, respectively), whereas preoperative coronary revascularization predicted less troponin elevations (adjusted ORs 0.35 and 0.16, p = 0.045 and 0.022, respectively). Postoperative ischemia (>10 min), the more so prolonged (>30 min) ischemia was the only independent predictor of troponin elevation if added with the preoperative predictors to the multivariate analysis (ORs 15.8 and 22.8, respectively, p < 0.001). CONCLUSIONS: Troponin elevations occur frequently after vascular surgery. They are strongly associated with postoperative ischemia, predicted by inducible ischemia on PTS, and reduced by preoperative coronary revascularization.

Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival after major vascular surgery.

OBJECTIVES: The aim of this study was to determine the long-term prognosis with postoperative markers of myocardial ischemia and infarction. BACKGROUND: Cardiac troponins (cTn) are superior to creatine kinase-MB fraction (CK-MB) in detecting perioperative myocardial infarction (PMI). However, their threshold levels signifying PMI and their long-term prognostic value are not yet determined. METHODS: A cohort of 447 consecutive patients who underwent 501 major vascular procedures was prospectively studied. Perioperative continuous 12-lead electrocardiogram monitoring, cardiac troponin-I (cTn-I) and/or cardiac troponin-T (cTn-T), and CK-MB levels on the first three postoperative days, and long-term survival were determined. The association of different cutoff levels of CK-MB, troponin, and ischemia duration with long-term survival was investigated. RESULTS: Between 14 (2.9%) and 107 (23.9%) of the patients sustained PMI, depending on the biochemical criteria used. Elevated postoperative CK-MB, cTn, and prolonged (>30 min) ischemia, at all cutoff levels examined, predicted long-term mortality independent of the preoperative predictors: patient's age, type of vascular surgery, previous myocardial infarction, and renal failure (Cox multivariate analysis). Both CK-MB >10% and cTn-I >1.5 ng/ml and/or cTn-T >0.1 ng/ml independently predicted a 3.75-fold and 2.06-fold increase in long-term mortality (p = 0.006 and 0.012, respectively). Similarly, both CK-MB >5% and cTn-I >0.6 ng/ml and/or cTn-T >0.03 ng/ml independently predicted a 2.15-fold and 1.89-fold increase in mortality (p = 0.018 and 0.01, respectively). Patients with both these markers elevated had a 4.19-fold increase in mortality (p < 0.001). CONCLUSIONS: Postoperative CK-MB and troponin, even at low cutoff levels, are independent and complementary predictors of long-term mortality after major vascular surgery.

Preoperative thallium scanning, selective coronary revascularization, and long-term survival after major vascular surgery.

BACKGROUND: Ischemia on thallium scanning is a strong predictor of long-term mortality in CAD patients. Whether coronary revascularization (CR) in patients with significant ischemia on preoperative thallium scanning (PTS) improves long-term survival after major vascular surgery has not been determined. METHODS AND RESULTS: The perioperative data, including PTS and subsequent CR in patients with moderate to severe reversible ischemia on PTS, and long-term survival of 502 consecutive patients who underwent 578 major vascular procedures were analyzed retrospectively. Patients with PTS who ultimately did not undergo the planned vascular operation were also studied. Cox regression and propensity score analyses were used to analyze survival. A total of 407 patients (81.1%) had PTS: 221 (54.3%) had no or mild defects (group I); 50 (12.3%) had moderate-severe fixed defects (group II); 62 (15.2%) had moderate-severe reversible ischemia yet did not undergo CR (group III); and 74 (18.2%) had moderate-severe reversible ischemia and subsequent CR by CABG (36) or PTCA (38; group IV). Patients who sustained major complications as a result of the preoperative cardiac workup were included in group IV. By multivariate analysis, age, type of vascular surgery, presence of diabetes, previous myocardial infarction, and moderate-severe ischemia on PTS independently predicted mortality (P=0.001, 0.009, 0.039, 0.006, and 0.029, respectively), and preoperative CR predicted improved survival (OR 0.52, P=0.018). Group IV had better survival than group III even when subdivided according to normal and reduced left ventricular function (OR 0.40 and 0.41, P=0.035 and 0.021, respectively). CONCLUSIONS: Long-term survival after major vascular surgery is significantly improved if patients with moderate-severe ischemia on PTS undergo selective CR.

Retroperitoneoscopic lumbar sympathectomy.

We present a series of 27 consecutive unselected patients who underwent 29 retroperitoneoscopic lumbar sympathectomies. There were 21 male patients and six female patients, with a mean age of 45 years (RANGE, 21 to 28 years). Twenty-two patients had ischemia of the lower limb, and five patients had severe reflex sympathetic dystrophy. The retroperitoneal space was developed with a balloon trocar inserted through a small incision in the flank. Additional trocars used for endoscopic instruments. The sympathetic chain from the ganglia second lumbar vertebrae to the fourth lumbar vertebrae was resected. The procedure was successfully accomplished in all the patients without any operative or postoperative complications. The mean operative time Was 136 minutes, and the mean hospital stay was 1.4 days. All the patients had significant improvement of pain or dystrophic changes. Retroperitoneoscopic lumbar sympathectomy successfully combines the advantages of minimally invasive surgery with the effectiveness of the open procedure.