Reversed and Antegrade Iliac Side Branch Stentgraft as an Alternative or Rescue Maneuver in Complex (Thoraco)Abdominal Endovascular Aortic Repair to Preserve Renal Perfusion.

PURPOSE: To describe a technique that can preserve renal perfusion in failed bridging stent implantation of renal arteries or as intentional procedure in emergency cases, when the (thoraco)abdominal aneurysm anatomy does not meet the criteria for instructions for use of an "off-the-shelf" graft. The technique is based on reversed or antegrade integration of a standard iliac side branch graft into the aortic stentgraft system, which allows cannulation of (accessory) renal vessels. TECHNIQUE: A standard iliac side branch prosthesis is deployed and re-sheathed in reversed direction on the back table. The endograft is then implanted in the unibody in analogy to an iliac limb. The iliac side branch is cannulated followed by target vessel cannulation and covered bridging stents are deployed for completion. Furthermore, an iliac side branch prothesis can also be used to preserve relevant accessory renal arteries, when implanted in delivered antegrade loading position. CONCLUSION: The use of a reversed and antegrade iliac side branch technique to revascularize renal vessels is feasible and safe in selected patients. This technique may also allow to extend the range of an "offthe- shelf" (multibranch) stentgraft, when immediate treatment is required.

Deletion of junctional adhesion molecule A from platelets increases early-stage neointima formation after wire injury in hyperlipidemic mice.

Platelets play an important role in the pathogenesis of vascular remodelling after injury. Junctional adhesion molecule A (JAM-A) was recently described to regulate platelet activation. Specific deletion of JAM-A from platelets resulted in increased reactivity and in accelerated progression of atherosclerosis. The aim of this study was to investigate the specific contribution of platelet-derived JAM-A to neointima formation after vascular injury. Mice with or without platelet-specific (tr)JAM-A-deficiency in an apolipoprotein e (apoe-/- ) background underwent wire-induced injury of the common carotid artery. Ex vivo imaging by two-photon microscopy revealed increased platelet coverage at the site of injury in trJAM-A-deficient mice. Cell recruitment assays showed increased adhesion of monocytic cells to activated JAM-A-deficient platelets than to control platelets. Inhibition of αM ß2 or GPIbα, but not of CD62P, suppressed those differences. Up to 4 weeks after wire injury, intimal neoplasia and neointimal cellular content were analysed. Neointimal lesion area was increased in trJAM-A-/- apoe-/- mice and the lesions showed an increased macrophage accumulation and proliferating smooth muscle cells compared with trJAM-A+/+ apoe-/- littermates 2 weeks, but not 4 weeks after injury. Re-endothelialization was decreased in trJAM-A-/- apoe-/- mice compared with controls 2 weeks after injury, yet it was complete in both groups after 4 weeks. A platelet gain of function by deletion of JAM-A accelerates neointima formation only during earlier phases after vascular injury, through an increased recruitment of mononuclear cells. Thus, the contribution of platelets might become less important when neointima formation progresses to later stages.

Hyperreactivity of junctional adhesion molecule A-deficient platelets accelerates atherosclerosis in hyperlipidemic mice.

RATIONALE: Besides their essential role in hemostasis, platelets also have functions in inflammation. In platelets, junctional adhesion molecule (JAM)-A was previously identified as an inhibitor of integrin αIIbß3-mediated outside-in signaling and its genetic knockdown resulted in hyperreactivity. OBJECTIVE: This gain-of-function was specifically exploited to investigate the role of platelet hyperreactivity in plaque development. METHODS AND RESULTS: JAM-A-deficient platelets showed increased aggregation and cellular and sarcoma tyrosine-protein kinase activation. On αIIbß3 ligation, JAM-A was shown to be dephosphorylated, which could be prevented by protein tyrosine phosphatase nonreceptor type 1 inhibition. Mice with or without platelet-specific (tr)JAM-A-deficiency in an apolipoprotein e (apoe(-/-)) background were fed a high-fat diet. After ≤12 weeks of diet, trJAM-A(-/-)apoe-/- mice showed increased aortic plaque formation when compared with trJAM-A(+/+) apoe(-/-) controls, and these differences were most evident at early time points. At 2 weeks, the plaques of the trJAM-A(-/-) apoe(-/-) animals revealed increased macrophage, T cell, and smooth muscle cell content. Interestingly, plasma levels of chemokines CC chemokine ligand 5 and CXC-chemokine ligand 4 were increased in the trJAM-A(-/-) apoe(-/-)mice, and JAM-A-deficient platelets showed increased binding to monocytes and neutrophils. Whole-blood perfusion experiments and intravital microscopy revealed increased recruitment of platelets and monocytes to the inflamed endothelium in blood of trJAM-A(-/-) apoe(-/-)mice. Notably, these proinflammatory effects of JAM-A-deficient platelets could be abolished by the inhibition of αIIbß3 signaling in vitro. CONCLUSIONS: Deletion of JAM-A causes a gain-of-function in platelets, with lower activation thresholds and increased inflammatory activities. This leads to an increase of plaque formation, particularly in early stages of the disease.

Vitamin K antagonism aggravates chronic kidney disease-induced neointimal hyperplasia and calcification in arterialized veins: role of vitamin K treatment?

Arteriovenous fistula (AVF) is the common vascular access type for a hemodialysis patient. Its failure is due to neointimal hyperplasia. Vitamin K antagonists are given to lower thrombosis tendency, but have side effects that enhance arterial calcifications. Here, we investigated the effects of vitamin K antagonists and vitamin K2 (K2) treatment on neointimal hyperplasia development and calcification in rats and in arterialized human veins. AVF was generated in female rats while chronic kidney disease (CKD) was induced using an adenine-enriched diet. Arterialization, CKD, and vitamin K antagonists all significantly enhanced venous neointimal hyperplasia. K2 treatment, additional to vitamin K antagonists, significantly reduced neointimal hyperplasia in arterialized veins in healthy rats but not in rats with CKD. Arterialization, CKD, and vitamin K antagonism all significantly increased, whereas K2 supplementation attenuated calcification in healthy rats and rats with CKD. K2 significantly enhanced matrix Gla protein carboxylation in control rats and rats with CKD. Arterialized human vein samples contained inactive matrix Gla protein at calcification and neointimal hyperplasia sites, indicating local vitamin K deficiency. Thus, vitamin K antagonists have detrimental effects on AVF remodeling, whereas K2 reduced neointimal hyperplasia and calcification indicating vasoprotective effects. Hence, K2 administration may be useful to prevent neointimal hyperplasia and calcification in arterialized veins

Selective renal blood perfusion induces renal tubules injury in a porcine model.

OBJECTIVE: Extracorporeal circulation is routinely used in thoracoabdominal aortic aneurysm repair to preserve blood perfusion. Despite this protective measure, acute and chronic kidney disorders can develop. Therefore, the aim of this study was to establish a new large-animal model to assess the efficacy of selective renal perfusion (SRP) with extracorporeal circulation in a setting of thoracoabdominal aortic aneurysm repair. METHODS: Eighteen pigs underwent a thoracolaparotomy, during with the aorta and renal arteries were exposed. The animals were divided into three cohorts of six pigs each: cohort I--control; cohort II--thoracic aortic clamping with distal aortic perfusion (DAP) using a roller pump; and cohort III--thoracic aortic clamping with DAP plus SRP. Kidney metabolism, kidney injury, and red blood cell damage were measured by oxygen extraction ratio (O2ER), neutrophil gelatinase-associated lipocalin, a marker for acute kidney damage, and serum free hemoglobin. RESULTS: With normal mean arterial blood pressures, flow rates in the renal arteries during perfusion decreased to 75% (group II) with DAP and to 50% (group III) with SRP compared with the control animals (group I; P = .0279 for I vs II; P = .0002 for I vs III). Microcirculation, measured by microspheres, did not differ significantly among the groups. In contrast, O2ER (P = .0021 for I vs III) and neutrophil gelatinase-associated lipocalin (P = .0083 for I vs III) levels were significantly increased in group III, whereas free hemoglobin was increased in groups II and III (P = .0406 for I vs II; P = .0018 for I vs III). CONCLUSIONS: SRP with a roller pump induces kidney tubule injury. Thus, distal aortic and SRP in our model does not provide adequate kidney protection. Furthermore, the perfusion system provokes red blood cell damage with increased free hemoglobin. Hence, the SRP perfusion technique should be revised and tested.

Microcirculatory perfusion shift in the gut wall layers induced by extracorporeal circulation.

OBJECTIVE: Extracorporeal circulation (ECC) is regularly applied to maintain organ perfusion during major aortic and cardiovascular surgery. During thoracoabdominal aortic repair, ECC-driven selective visceral arterial perfusion (SVP) results in changed microcirculatory perfusion (shift from the muscularis toward the mucosal small intestinal layer) in conjunction with macrohemodynamic hypoperfusion. The underlying mechanism, however, is unclear. Therefore, the aim of this study was to assess in a porcine model whether ECC itself or the hypoperfusion induced by SVP is responsible for the mucosal/muscular shift in the small intestinal wall. METHODS: A thoracoabdominal aortic approach was performed in 15 healthy pigs divided equally into three groups: group I, control; group II, thoracic aortic cross-clamping with distal aortic perfusion; and group III, thoracic aortic cross-clamping with distal aortic perfusion and SVP. Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurement and fluorescent microspheres. In addition, markers for metabolism and intestinal ischemia-reperfusion injury were determined. RESULTS: ECC with a roller pump induced a significant switch from the muscularis and mucosal layer of the small intestine, even with adequate macrocirculation (mucosal/muscular perfusion ratio: group I vs II, P = .005; group I vs III, P = .0018). Furthermore, the oxygen extraction ratio increased significantly in groups II (>30%) and III (>40%) in the beginning of the ECC compared with the control (group I vs II, P = .0037; group I vs III, P = .0062). Lactate concentrations and pH values did not differ between groups I and II; but group III demonstrated a significant shifting toward a lactate-associated acidosis (lactate: group I vs III, P = .0031; pH: group I vs III, P = .0001). CONCLUSIONS: We demonstrated a significant shifting between the small intestinal gut wall layers induced by roller pump-driven ECC. The shift occurs independently of macrohemodynamics, with a significant effect on aerobic metabolism in the gut wall. Consequently, an optimal intestinal perfusion cannot be guaranteed by a roller pump; therefore, perfusion techniques need to be optimized.

Vascular compression syndromes.

Dealing with vascular compression syndromes is one of the most challenging tasks in Vascular Medicine practice. This heterogeneous group of disorders is characterised by external compression of primarily healthy arteries and/or veins as well as accompanying nerval structures, carrying the risk of subsequent structural vessel wall and nerve damage. Vascular compression syndromes may severely impair health-related quality of life in affected individuals who are typically young and otherwise healthy. The diagnostic approach has not been standardised for any of the vascular compression syndromes. Moreover, some degree of positional external compression of blood vessels such as the subclavian and popliteal vessels or the celiac trunk can be found in a significant proportion of healthy individuals. This implies important difficulties in differentiating physiological from pathological findings of clinical examination and diagnostic imaging with provocative manoeuvres. The level of evidence on which treatment decisions regarding surgical decompression with or without revascularisation can be relied on is generally poor, mostly coming from retrospective single centre studies. Proper patient selection is critical in order to avoid overtreatment in patients without a clear association between vascular compression and clinical symptoms. With a focus on the thoracic outlet-syndrome, the median arcuate ligament syndrome and the popliteal entrapment syndrome, the present article gives a selective literature review on compression syndromes from an interdisciplinary vascular point of view.

Treatment of type I endoleaks using transcatheter embolization with onyx.

PURPOSE: To report a single-center experience with transcatheter embolization of type I endoleaks using the liquid embolic agent Onyx, an ethylene vinyl alcohol copolymer. METHODS: Eight patients (4 men; mean age 74.8 years, range 63-86) with 10 type I endoleaks (6 abdominal and 4 thoracic) diagnosed 2 days to 9 years after endovascular repair were treated with Onyx embolization because cuff extension was precluded by an insufficient landing zone in 6 cases and an unsuitable aortic diameter in 2. Endoleaks were accessed with a 4-F diagnostic catheter and a coaxially introduced dimethylsulfoxide-compatible microcatheter. Onyx-34 was predominantly applied due to its high viscosity; patent side branches were coil embolized prior to Onyx delivery in 3 cases. RESULTS: Technical success of the procedure was achieved in all cases. The mean volume of Onyx used for abdominal endoleaks was 11.8 mL (range 3.0-25.5) and 19.4 mL (range 4.5-31.5) for thoracic endoleaks. The average duration of the procedure was 76.7 minutes (range 34.5-110.6), and the average radiation dose area product was 18.8 cGy*cm (2) (range 10.6-55.8). Reperfusion of the endoleak was detected in one case 2 days after the procedure. A second case showed an occluded endoleak but a small trace of contrast between the aortic wall and the stent-graft. Non-target embolization was not found in any case. Mean follow-up was 13.2 months (range 8-24). The mean reduction in diameters for thoracic aneurysms after 6 and 12 months was 0.4 and 0.9 cm, respectively, and 0.6 and 1.2 cm, respectively, for abdominal aneurysms. CONCLUSION: Transcatheter embolization of type I endoleaks using Onyx is a simple, safe, and sustainable treatment option with a high primary success rate for cases in which stent-graft extension is not possible. The benefit of additional coil embolization remains uncertain.

The impact of selective visceral perfusion on intestinal macrohemodynamics and microhemodynamics in a porcine model of thoracic aortic cross-clamping.

INTRODUCTION: Despite its presumed effectiveness and clinical use, the physiology of selective visceral perfusion combined with distal aortic perfusion during open thoracoabdominal aortic surgery has not been characterized. Thus, the aim of this study was to establish a translatable model of thoracic aortic-clamping to assess the effect of selective visceral perfusion with added distal aortic perfusion on local intestinal macrohemodynamics and microhemodynamics, intestinal histopathology, and markers of inflammation and intestinal damage. METHODS: A thoracolaparotomy was performed in 15 pigs, and the aorta was exposed, including the origins of celiac trunk and superior mesenteric artery. The animals were divided into three cohorts: control (I), thoracic aortic cross-clamping (II), and thoracic aortic cross-clamping with selective visceral perfusion plus distal aortic perfusion using extracorporeal circulation (III). Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurements and fluorescent microspheres. Intestinal ischemia-reperfusion injury was determined by the analysis of perioperative intestinal fatty acid-binding protein (IFABP) and interleukin-8 (IL-8) levels and correlated with histopathologic changes. RESULTS: Severe intestinal tissue injury and an inflammatory response were observed in cohort II compared with cohort III for IL-8 (38.2 vs 3.56 pg/mL; P = .04). The procedure in cohort III resulted in a flow and pressure-associated intestinal hypoperfusion compared with cohort I in the superior mesenteric artery (mean blood pressure, 24.1 ± 10.4 vs 67.2 ± 7.4 mm Hg; P < .0001; mean flow rates: 353.3 ± 133.8 vs 961.7 ± 310.8 mL/min; P < .0001). This was paralleled in cohort III vs cohort I by a significant mucosal injury (IFABP, 713 ± 307.1 vs 170 ± 115.4 pg/mL; P = .014) despite a profound recruitment of intestinal microcirculation (338% ± 206.7% vs 135% ± 123.7%; P = .05). CONCLUSIONS: This study reports a novel large-animal model of thoracic aortic cross-clamping that allows the study of visceral perfusion strategies. However, we demonstrated with IL-8 and IFABP measurements that thoracoabdominal aortic aneurysm surgery with selective visceral perfusion and distal aortic perfusion is superior to the clamp-and-sew technique, even though small intestinal tissue damage cannot be completely avoided by selective visceral perfusion and distal aortic perfusion. In any case, this model seems to be a platform to evaluate and optimize measures for gut wall protection.

Management of thoracic aortic lesions--the future is endovascular.

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the "state-of-the-art" treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.

Endovascular entry closure of a late type A aortic dissection after implantation of a self-expanding transcatheter heart valve (Evolut R): a case report.

BACKGROUND: Late Stanford type A aortic dissections (TAADs) are a very rare complication after transcatheter aortic valve implantation (TAVI). Surgery is the treatment of choice, but perioperative mortality (25%) and neurological complications (18%) remain high. CASE SUMMARY: An 85-year-old male patient presented with acute chest pain 5 months after a transfemoral Evolut R 34 mm transcatheter heart valve (THV) implantation. On multi-slice computed tomography (MSCT) a TAAD was found with a 7 mm primary entry at the supra-annular aortic edge of the THV expanding to the innominate artery without re-entry. Due to extensive comorbidities including two bypass operations in the history, the Heart Team declined surgery. Within 6 months of watchful waiting the maximal aortic diameter (MAD) increased from 57 to 62 mm. The decision was made to perform an endovascular closure of the inflow to the false lumen by implanting a 25 mm Amplatzer™ Cribriform Septal Occluder. MSCT 4 weeks after occlusion showed the false lumen almost completely filled with thrombus, MSCT 3 months later showed a MAD reduction to 55 mm with shrinkage of the false lumen. DISCUSSION: Presumably, the late TAAD was caused by the supra-annular edge of the Evolut-stent. Because of the extreme risk surgical repair was not an option and a stent graft would have occluded the vein grafts. This case shows that in absence of any other treatment options endovascular closure of the entry to the false lumen can be successfully performed in a TAAD after TAVI.

Chronic kidney disease aggravates arteriovenous fistula damage in rats.

Neointimal hyperplasia (NIH) and impaired dilatation are important contributors to arteriovenous fistula (AVF) failure. It is unclear whether chronic kidney disease (CKD) itself causes adverse remodeling in arterialized veins. Here we determined if CKD specifically triggers adverse effects on vascular remodeling and assessed whether these changes affect the function of AVFs. For this purpose, we used rats on a normal diet or on an adenine-rich diet to induce CKD and created a fistula between the right femoral artery and vein. Fistula maturation was followed noninvasively by high-resolution ultrasound (US), and groups of rats were killed on 42 and 84 days after surgery for histological and immunohistochemical analyses of the AVFs and contralateral femoral vessels. In vivo US and ex vivo morphometric analyses confirmed a significant increase in NIH in the AVFs of both groups with CKD compared to those receiving a normal diet. Furthermore, we found using histological evaluation of the fistula veins in the rats with CKD that the media shrank and their calcification increased significantly. Afferent artery dilatation was significantly impaired in CKD and the downstream fistula vein had delayed dilation after surgery. These changes were accompanied by significantly increased peak systolic velocity at the site of the anastomosis, implying stenosis. Thus, CKD triggers adverse effects on vascular remodeling in AVFs, all of which contribute to anatomical and/or functional stenosis.

Hemolysis is associated with acute kidney injury during major aortic surgery.

Hemolysis is an inevitable side effect of cardiopulmonary bypass resulting in increased plasma free hemoglobin that may impair tissue perfusion by scavenging nitric oxide. Acute kidney injury after on-pump cardiovascular surgery arises from a number of causes and severely affects patient morbidity and mortality. Here, we studied the effect of acute hemolysis on renal injury in 35 patients undergoing on-pump surgical repair of thoracic and thoracoabdominal aortic aneurysms of whom 19 experienced acute kidney injury. During surgery, plasma free hemoglobin increased, as did urinary excretion of the tubular injury marker N-acetyl-beta-D-glucosaminidase, in patients with and without acute kidney injury, reaching peak levels at 2 h and 15 min, respectively, after reperfusion. Furthermore, plasma free hemoglobin was independently and significantly correlated with the urine biomarker, which, in turn, was independently and significantly associated with the later postoperative increase in serum creatinine. Importantly, peak plasma free hemoglobin and urine N-acetyl-beta-D-glucosaminidase concentrations had significant predictive value for postoperative acute kidney injury. Thus, we found an association between increased plasma free hemoglobin and renal injury casting new light on the pathophysiology of acute kidney injury. Therefore, free hemoglobin is a new therapeutic target to improve clinical outcome after on-pump cardiovascular surgery.

Brain and spinal cord protection during simultaneous aortic arch and thoracoabdominal aneurysm repair.

OBJECTIVE: We assessed the surgical and neurological outcome of patients undergoing simultaneous repair of aortic arch and descending thoracic aortic aneurysms (DTAA) or thoracoabdominal aortic aneurysms (TAAA) via left thoracotomy or thoracolaparotomy. METHODS: During a 6-year period, we performed 32 procedures in 23 male and 9 female patients with DTAA or TAAA with concomitant aortic arch aneurysms. The mean age of the patients was 50.9 years (range, 18-75 years). Twenty-two patients suffered from DTAA, 4 had type-I TAAA, and 6 had type-II TAAA. The entire aortic arch was involved in 12 patients and the distal hemi-arch in 20 patients. The mean diameter of the aneurysms was 6 cm (range, 4.9-7.6 cm). All patients were operated on according to the protocol with cerebrospinal fluid drainage, distal aortic and selective organ perfusion, as well as antegrade brain perfusion. Neuromonitoring was performed by means of motor evoked potentials (MEPs), transcranial Doppler (TCD), and electroencephalography (EEG). RESULTS: All patients survived the surgical procedure and 30-day mortality did not occur. At the end of the procedure, all patients had adequate MEPs, TCD, and EEG. One patient died 47 days after operation due to gastrointestinal bleeding and therapy-resistant coagulopathy. Major postoperative complications like paraplegia or paraparesis, renal failure, and myocardial infarction were not encountered. One patient had a stroke but neurological deficits were irrelevant. Mean preoperative creatinine level was 125 mmol/L, which peaked to a mean maximal level of 130 and returned to 92 mmol/L at discharge. Other complications included bleeding requiring surgical intervention (n = 4), arrhythmia (n = 1), pneumonia (n = 5), and respiratory distress syndrome (n = 2). At a median follow-up of 38 months, all but 1 patient was alive and free of re-intervention. CONCLUSION: Single-stage repair of aortic arch and concomitant thoracic and thoracoabdominal aortic aneurysms via left-sided thoracotomy or thoraco-laparotomy yields excellent short- and midterm outcomes. Monitoring of cerebral and spinal cord function contributes to improved neurologic outcome.

Unmasking pedal arteries in patients with critical ischemia using time-resolved contrast-enhanced 3D MRA.

OBJECTIVE: To test the diagnostic relevance of fast Gadobenate dimeglumine (Gd-BOPTA) enhanced, time-resolved, three-dimensional magnetic resonance angiography (t3D MRA) of distal calf and pedal vasculature in critical limb ischemia in a prospective comparison with conventional selective digital subtraction angiography (DSA) and high-resolution duplex ultrasound (US) scan. METHODS: From April 2007 to June 2008, 34 feet of 29 consecutive patients suffering from limb-threatening ischemia underwent diagnostic US scan, DSA, and t3D MRA before treatment. The investigations took place within 3 days. A t3D MRA was performed using a 3 Tesla whole-body magnetic resonance (MR) system with an eight-element phased-array coil. Image quality and diagnostic findings were subjectively analyzed by two radiologists and one vascular surgeon. Each distal calf and foot was divided into six arterial segments for DSA and t3D MRA, and four segments were investigated by US scan. Patency or occlusion was studied with all the techniques, whereby DSA and t3D MRA were additionally evaluated in patients having greater or less than 50% stenosis. Finally, images were visually assessed by the three observers by applying a six-point grading scale. The acquired data was statistically analyzed using McNemar's test and Wilcoxon's matched-pairs signed-rank sum test. The P values of less than an alpha level of .05 were considered to be statistically significant. RESULTS: We achieved MRA images of diagnostic quality in all patients. Significantly more patent pedal arteries were identified by applying t3D MRA than DSA (P < .001) and US scan (P < .02). For estimating the degree of stenosis, no technique proved to be superior (P > .28). Overall image quality was rated best for t3D MRA. Additionally, potential bypass target vessels could be clearly discriminated from pedal veins due to the temporal resolution. CONCLUSION: In our prospective study, t3D MRA has been proven to be superior to DSA and US scan in pedal vasculature imaging in critical limb ischemia. This is a valuable, noninvasive method for detecting potential pedal bypass target arteries.

Functional and structural response of arterialized femoral veins in a rodent AV fistula model.

BACKGROUND: Neointimal hyperplasia is considered to be the major cause of arteriovenous fistula (AVF) failure, resulting in vein wall thickening, stenosis and, ultimately, occlusion. Ultrasound (US) has been shown to be effective for detecting these morphological changes in patients. The aim of this study was to develop an experimental AVF model in the rat that shows typical features of fistula maturation and allows longitudinal monitoring of fistula veins by high-resolution ultrasound. METHODS: AVFs were created by a handsewn end-to-side anastomosis between the femoral vein and the femoral artery in 15 rats. A group of sham-operated animals (n = 3) served as controls. Time-related functional and morphological AVF characteristics were assessed up to 12 weeks using ultrasound (15-MHz transducer) and were correlated to histopathological changes. RESULTS: All rats survived surgery, and the patency rate was 93%. US showed a 2-fold increase in the fistula vein diameter and mean flow velocity as well as a 4-fold increase in the intima-media thickness without significant luminal loss. The afferent femoral artery exhibited no change in intima-media thickness and only minimal adaptive increases in diameter and flow velocity. Histological evaluation confirmed these observations. CONCLUSIONS: Our AVF model in the rat demonstrates maturation effects in fistula veins similar to typical clinical findings in haemodialysis patients. Noninvasive ultrasound proved to be a valuable tool for longitudinal in vivo monitoring of the fistulas in this rodent model.

Visceral injury and systemic inflammation in patients undergoing extracorporeal circulation during aortic surgery.

OBJECTIVES: Visceral injury and inflammation are evaluated in patients undergoing extracorporeal circulation (ECC) either with distal aortic perfusion (DAP) during thoracic aortic aneurysm (TAA) repair or DAP and selective organ perfusion (DAP and SP) during thoracoabdominal aortic aneurysm (TAAA) repair. SUMMARY BACKGROUND DATA: Visceral hypoperfusion and subsequent visceral injury, mainly to the gut, have been implicated as central events in the development of systemic inflammatory response syndrome (SIRS) and organ dysfunction after major surgery. Patients undergoing DAP or DAP and SP are exposed to artificial visceral perfusion, potentially leading to the development of intestinal injury and systemic inflammation. METHODS: To assess visceral injury arteriovenous differences of fatty acid binding proteins were measured for the gut (I-FABP and L-FABP) and left kidney (L-FABP) along with systemic plasma concentrations. Systemic ALT was used as liver injury marker. Plasma IL-6 and IL-8 denoted systemic inflammation. RESULTS: During ECC systemic I-FABP and L-FABP levels increased in both groups, representing intestinal injury. Significantly elevated levels of I-FABP (P < 0.001) and L-FABP (P < 0.001) were found in the DAP and SP group, after ECC was stopped and normal circulation restored. Liver and renal tubular cell injury was not detected. Significant increases in systemic IL-6 and IL-8 values were measured only in patients undergoing DAP and SP. Additionally, the extent of intestinal injury correlated positively with systemic inflammation. CONCLUSIONS: This study shows the development of intestinal mucosal injury during ECC with DAP or DAP and SP, indicative of insufficient intestinal perfusion. Intestinal injury was associated with a systemic pro-inflammatory response.

Intestinal barrier dysfunction in developing liver cirrhosis: An in vivo analysis of bacterial translocation.

AIM: Transmucosal passage of bacteria across the intestine, the essential step for bacterial translocation, has been identified as a key event in the pathogenesis of life-threatening infections in cirrhosis. Existing animal models of liver cirrhosis only provide indirect information about the pathogenesis of such infections. The aim of this study has been to assess transmucosal passage and bacterial translocation directly in vivo using a rat model of developing liver cirrhosis. METHODS: Male Sprague Dawley rats were randomly assigned to two groups: controls and animals with developing liver cirrhosis induced by s.c. injection of carbon tetrachloride. In anesthetized animals a suspension of green fluorescent protein (GFP)-tagged E. coli was administered into the terminal ileum. Time intervals necessary for translocation of E. coli into the mucosa and muscularis were assessed by intravital microscopy and translocation of E. coli in mesentery, liver and spleen was determined microbiologically. RESULTS: Bacterial kinetics at the level of the mucosa and muscularis showed significant enhancement in cirrhotic rats compared to the controls (P < 0.001). GFP-expressing E. coli were detected in the mesentery, liver and spleen of animals with cirrhosis taken one hour after E. coli administration. However, cultures of control animals remained sterile. CONCLUSION: Intravital microscopy of fluorescent bacteria represents a novel approach to studying bacterial translocation in vivo. Here we report that this technique can be used to visualize bacterial transit in in vivo and gives further support to the transmucosal passage of bacteria across the intestine correlating with bacterial translocation in CCl(4)-induced liver cirrhosis.

Enhanced iNOS gene expression in the steatotic rat liver after normothermic ischemia.

BACKGROUND: Impaired hepatic microcirculation in the steatotic liver has been identified as a considerable factor for increased vulnerability after ischemia/reperfusion (I/R). Changes in regulation and synthesis of vasoactive mediators, such as nitric oxide (NO) and endothelin (ET-1), may result in functional impairment of postischemic sinusoidal perfusion. The aim of the current study was to assess the impact of I/R injury on postischemic gene expression of NO and ET-1 in steatotic livers. MATERIALS AND METHODS: Male Sprague-Dawley rats with or without hepatic steatosis (induced by carbon tetrachloride treatment) were subjected to normothermic I/R injury. Steady-state mRNA levels were assessed using RT-PCR to study the expression of genes encoding ET-1, NO synthase (endothelial cell NO synthase and inducible NO synthase, iNOS). Immunohistochemistry was performed for detection of iNOS. RESULTS: I/R injury was followed by increased iNOS gene expression (RT-PCR/immunohistochemistry) in animals with hepatic steatosis, predominately in hepatocytes with fatty degeneration. A mild increase in mRNA levels for ET-1 was found in steatotic rat livers. I/R induced a further increase in ET-1 gene expression in some but not all reperfused steatotic livers. CONCLUSIONS: We show an enhanced gene expression of iNOS in postischemic steatotic rat livers. Hepatocytes with fatty degeneration appear to be the major source for NO generation. Furthermore, I/R may also induce ET-1 gene expression. Dysregulation of sinusoidal perfusion by NO and ET-1 is therefore likely to contribute to I/R injury of the steatotic liver.