A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure

ObjectiveAn ideal animal model of abdominal aortic aneurysm (AAA) is of great importance for clarifying unknown complex mechanisms of the pathogenesis. We introduce a new, simple technique to create reliable AAAs that simulate human aneurysms.MethodsExperimental models of AAAs were created in 71 rats by means of a 20-minute application of intraluminal elastase (30 U) and extraluminal calcium chloride (0.5M) in the 1-cm segment of infrarenal abdominal aorta (group EC, n = 26). A single application of elastase (group E, n = 24) or calcium chloride (group C, n = 21) was used as control. The treated aorta in each group was measured under physiologic conditions and harvested at 1 and 4 weeks. Successful AAA formation was defined as a dilation ratio >50%. Inflammatory response, elastolytic activity, and histology in the treated aorta were evaluated among the three groups.ResultsThe surgical procedure in each group was similarly completed for approximate 30 minutes and performed without any technical failure or operative death. At 4 weeks, the dilation ratio and wall thickness were 94.8% ± 9.9% and 125.4 ± 5.6 μm in group EC, 43.3% ± 6.3% and 149.6 ± 6.5 μm in group E, and 10.9% ± 4.2% and 152.9 ± 7.2 μm in group C. The success rate of AAA formation in group EC (92.7%) was significantly higher than that in group E (25.0%) and group C (0.0%). Less elastin content in the aortic wall was observed in group EC. At 1 week, tumor necrosis factor-α and interleukin-1β messenger RNA (mRNA) expressions were significantly upregulated, and CD3+ and CD11b+ cells were significantly infiltrated into the treated aorta of group EC, compared with groups E or C. Gelatinolytic activities and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were also significantly activated in group EC.ConclusionThe rat AAA model using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure is simple and easy to perform and is highly reliable and reproducible to create a saccular aneurysm similar to human AAAs. This model could be more useful to clarify AAA pathogenesis, mechanisms, and treatment interventions in experimental researches.Clinical RelevanceAbdominal aortic aneurysm (AAA) typically has a silent nature, and its rupture has high morbidity and mortality. There are currently no therapeutic approaches to prevent AAA, and complete mechanisms of AAA formation are still poorly understood. We developed a novel rat AAA model using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure. This model is simple and easy to perform and is highly reliable and reproducible to create a saccular aneurysm. It could become a powerful tool not only to elucidate etiopathogenetic mechanisms of AAA formation but also to explore new diagnostic and therapeutic possibilities

Autologous fibrin-coated small-caliber vascular prostheses improve antithrombogenicity by reducing immunologic response

ObjectiveWe have recently developed a thrombin-free fibrin-coated vascular prosthesis that has a high performance rate in producing graft antithrombogenicity. We hypothesized that autologous, compared with xenologous, fibrin coatings could improve the antithrombogenicity of grafts by reducing immunologic response.MethodsAutologous fibrin-coated vascular prostheses and/or xenologous fibrin-coated vascular prostheses (internal diameter, 2 mm; length, 2.5 cm) were implanted in the bilateral carotid arteries of 50 Japanese white rabbits. They were classified into 2 groups by the selection of grafts in the individual: group I (autologous fibrin-coated vascular prosthesis and xenologous fibrin-coated vascular prosthesis); and group II (group IIa: both autologous fibrin-coated vascular prostheses, or group IIx: both xenologous fibrin-coated vascular prostheses). During a maximum of 180 days after implantation, we evaluated the thrombotic, inflammatory, and immunologic responses associated with both types of graft.ResultsAll grafts were patent at each end point. In group I, both platelet deposition and anti-graft antibodies in autologous fibrin-coated vascular prostheses were significantly less than those in xenologous fibrin-coated vascular prostheses until postoperative day 30. At postoperative day 10, there were significantly fewer CD45-positive infiltrating cells in autologous fibrin-coated vascular prostheses, and intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and nuclear factor-kappa B expression in autologous fibrin-coated vascular prostheses were less than those in xenologous fibrin-coated vascular prostheses. The neointimal hyperplasia in autologous fibrin-coated vascular prostheses was significantly decreased at postoperative day 180. In group II, serial changes of serum levels of immunoglobulin M, immunoglobulin G, interleukin-1β, and tissue-type plasminogen activator/plasminogen activator inhibitor-1 ratio in autologous fibrin-coated vascular prostheses were significantly less than those in xenologous fibrin-coated vascular prostheses. In both grafts, platelet deposition significantly correlated with serum immunoglobulin G level and tissue-type plasminogen activator/plasminogen activator inhibitor-1 ratio.ConclusionThese findings suggest that autologous fibrin coating in thrombin-free fibrin-coated vascular prostheses improve antithrombogenicity by reducing immunologic response and have a potential for clinical use in hybrid small-caliber vascular grafts

Sinus node dysfunction after repair of partial anomalous pulmonary venous connection

ObjectivesSinus node dysfunction is known as a major complication after repair of partial anomalous pulmonary venous connection. We retrospectively analyzed the results of the atrial wall flap technique compared with the results of patch repair or direct suturing in the intra-atrial tunnel technique.MethodsBetween 1991 and 2007, 23 patients (mean age, 6 years; range, 5 months–17 years) with partial anomalous pulmonary venous connection underwent surgical intervention. The right anomalous pulmonary veins drained to either the right atrium or superior vena cava in 8 and 15 patients, respectively. Patients were divided into 2 groups: group F (n = 14), who had repair with an atrial flap, and group N (n = 9), who had repair without an atrial flap. All patients had normal sinus rhythm preoperatively.ResultsNo patients had signs of superior vena cava or pulmonary venous obstruction within a mean follow-up of 4.8 years. One patient in group F required pacemaker implantation. In the early postoperative period, sinus node dysfunction developed in 93% of group F and 44% of group N patients (P < .01) and was prolonged until discharge in 57% of group F and 0% of group N patients (P < .01). At the most recent clinical visit, sinus node dysfunction was identified in 50% of group F patients, whereas all patients in group N had normal sinus rhythm (P < .02).ConclusionsThe atrial flap technique, which requires incision or suture crossing the crista terminalis, could cause sinus node dysfunction, whereas the intra-atrial rerouting method with a patch or direct suture maintains normal sinus node function postoperatively

Early patency rate and fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms

ObjectivesThe present study analyzes the early patency of intercostal artery reconstruction, using graft interposition and aortic patch anastomosis, and determines the fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms.MethodsWe selected 115 patients (mean age, 63 ± 15 years; range, 19-83 years; male, n = 83) treated by thoracoabdominal aortic aneurysm repair with 1 or more reconstructed intercostal arteries at the Kobe University Graduate School of Medicine between October 1999 and December 2012. The intercostal arteries were reconstructed using graft interposition (n = 66), aortic patch anastomosis (n = 42), or both (n = 7).ResultsThe hospital mortality rate was 7.8% (n = 9). Eleven patients (9.6%) developed spinal cord ischemic injury (permanent, n = 6, transient, n = 5). The average number of reconstructed intercostal arteries per patient was 3.0 ± 1.5 (1-7), and 345 intercostal arteries were reattached. The overall patency rate was 74.2% (256/345) and that of aortic patch anastomosis was significantly better than that of graft interposition (90.8% [109/120] vs 65.3% [147/225], P < .01), but significantly worse for patients with than without spinal cord ischemic injury (51.9% [14/27] vs 76.1% [242/318], P = .01). There was no patch aneurysm in graft interposition during a mean of 49 ± 38 (range, 2-147) postoperative months, but aortic patch anastomosis including 4 intercostal arteries became dilated in 2 patients.ConclusionsAortic patch anastomosis might offer better patency rates and prevent spinal cord ischemic injury compared with graft interposition. Although aneurysmal changes in intercostal artery reconstructions are rare, large blocks of aortic wall reconstruction should be closely monitored

Effect of atherothrombotic aorta on outcomes of total aortic arch replacement

ObjectiveThe effect of an atherothrombotic aorta on the short- and long-term outcomes of total aortic arch replacement, including postoperative neurologic deficits, remains unknown. We evaluated this relationship and also elucidated the synergistic effect of multiple other risk factors, in addition to an atherothrombotic aorta, on the neurologic outcome.MethodsA group of 179 consecutive patients undergoing total aortic arch replacement were studied. An atherothrombotic aorta was present in 34 patients (19%), more than moderate leukoaraiosis in 71 (39.7%), and significant extracranial carotid artery stenosis in 27 (15.1%). In-hospital deaths occurred in 2 patients, 1 (2.9%) of 34 patients with and 1 (0.7%) of 145 patients without an atherothrombotic aorta (P = .26). Permanent neurologic deficits occurred in 4 (2.2%) and transient neurologic deficits in 17 (9.5%) patients. Multivariate analysis demonstrated that the risk factors for transient neurologic deficits were an atherothrombotic aorta (odds ratio, 4.4), extracranial carotid artery stenosis (odds ratio, 5.5), moderate/severe leukoaraiosis (odds ratio, 3.6), and cardiopulmonary bypass time (odds ratio, 1.02). To calculate the probability of transient neurologic deficits, the following equation was derived: probability of transient neurologic deficits = {1 + exp [7.276 − 1.489 (atherothrombotic aorta) − 1.285 (leukoaraiosis) − 1.701 (extracranial carotid artery stenosis) − 0.017 (cardiopulmonary bypass time)]}−1. An exponential increase occurred in the probability of transient neurologic deficits with presence of an atherothrombotic aorta and other risk factors in relation to the cardiopulmonary bypass time. Survival at 3 years after surgery was significantly reduced in patients with vs without an atherothrombotic aorta (75.0% ± 8.8% vs 89.2% ± 3.1%, P = .01).ConclusionsPatients with an atherothrombotic aorta and associated preoperative comorbidities might be predisposed to adverse short- and long-term outcomes, including transient neurologic deficits