Geert Willem H. Schurink

Cerebral hyperperfusion syndrome

Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy is characterised by ipsilateral headache, hypertension, seizures, and focal neurological deficits. If not treated properly it can result in severe brain oedema, intracerebral or subarachnoid haemorrhage, and death. Knowledge of CHS among physicians is limited. Most studies report incidences of CHS of 0-3% after carotid endarterectomy. CHS is most common in patients with increases of more than 100% in perfusion compared with baseline after carotid endarterectomy and is rare in patients with increases in perfusion less than 100% compared with baseline. The most important risk factors in CHS are diminished cerebrovascular reserve, postoperative hypertension, and hyperperfusion lasting more than several hours after carotid endarterectomy. Impaired autoregulation as a result of endothelial dysfunction mediated by generation of free oxygen radicals is implicated in the pathogenesis of CHS. Treatment strategies are directed towards regulation of blood pressure and limitation of rises in cerebral perfusion. Complete recovery happens in mild cases, but disability and death can occur in more severe cases. More information about CHS and early institution of adequate treatment are of paramount importance in order to prevent these potentially severe complications.

Serum C-Reactive Protein Level Is Associated With Abdominal Aortic Aneurysm Size and May Be Produced by Aneurysmal Tissue

Background—Abdominal aortic aneurysms (AAA) are characterized by extensive transmural inflammation and C-reactive protein (CRP) has emerged as an independent risk factor for the development of cardiovascular disease. Therefore, we evaluated a possible association between serum CRP and aneurysm dimension in patients with asymptomatic AAA. Furthermore, the possibility of CRP production by aneurysmal tissue has been examined. Methods and Results—Serum CRP was determined highly sensitive (hs CRP) and aneurysmal size was measured in 39 patients with AAA. The presence of CRP mRNA was assessed in the aneurysmal tissue of 16 patients. Mean (SD) hs CRP was 3.23 (2.96) mg/L. After log-transformation, hs CRP correlated significantly with aneurysmal size (r =0.477, P =0.002). When the patients were divided into 3 equally sized groups according to hs CRP level, aortic diameter increased from lowest to upper hs CRP-tertile (49 mm, 61 mm, and 67 mm, respectively;P <0.05 for 3rd versus 1st tertile). This association persisted after correction for risk factors. CRP mRNA was found in 25% of aneurysmal aortic tissues. Conclusions—This is the first report showing that serum hs CRP is associated with aneurysmal size and that—in at least some patients—CRP may be produced by aneurysmal tissue. These data underscore the inflammatory nature of AAA formation, suggesting that serum hs CRP may serve as a marker of AAA disease and that CRP produced in vascular tissue might contribute to aneurysm formation.

Endoleakage after stent-graft treatment of abdominal aneurysm: Implications on pressure and imaging—an in vitro study

BACKGROUND Endoleakage is a fairly common problem after endovascular repair of abdominal aortic aneurysm and may prevent successful exclusion of the aneurysm. The consequences of endoleakage in terms of pressure in the aneurysmal sac are not exactly known. Moreover, the diagnosis of endoleakage is a problem because visualization of endoleaks can be difficult. METHOD With an ex vivo model of circulation with an artificial aneurysm managed by means of a tube graft, studies were performed to evaluate precisely known diameters of endoleaks with both imaging techniques (computed tomography and digital subtraction angiography) and pressure measurements of the aneurysmal sac. The experiments were performed without endoleak (controls) and with 1.231-French (0.410 mm), 3-French (1 mm), and 7-French (2.33 mm) endoleaks. Pressure and imaging were evaluated in the absence and presence of a simulated open lumbar artery. The pressure in the prosthesis and in the aneurysmal sac were recorded simultaneously. Digital subtraction angiography with and without a Lucite acrylic plate, computed tomographic angiography, and delayed computed tomographic angiography were performed. For the first experiments, the aneurysmal sac was filled with starch solution. All tests were repeated with fresh thrombus in the aneurysmal sac. RESULTS Each endoleak was associated with a diastolic pressure in the aneurysmal sac that was identical to diastolic systemic pressure, although the pressure curve was damped. At digital subtraction angiography without a Lucite acrylic plate, the 1.231-French (0.410 mm) endoleak was visualized without an open lumbar artery. When a Lucite acrylic plate was added, the endoleak was not visible until a lumbar artery was opened. In the presence of thrombus within the aneurysmal sac, all endoleaks were not visualized at digital subtraction angiography. At computed tomographic angiography, all endoleaks were not visualized in the absence of a thrombus mass in the aneurysmal sac. In the presence of thrombus within the aneurysmal sac, the 1.231-French (0.410 mm) endoleak became visible after opening of a simulated lumbar artery. At delayed computed tomographic angiography, all endoleaks were visualized without and with thrombus. CONCLUSION Every endoleak, even a very small one, caused pressure greater than systemic diastolic pressure within the aneurysmal sac. However, small endoleaks were not visualized with digital subtraction angiography and computed tomographic angiography, whereas all endoleaks were visualized with a delayed computed tomographic angiography protocol. We believe that follow-up examinations after stent graft placement for aortic aneurysms should focus on pressure measurements, but until this is clinically feasible, delayed computed tomographic angiography should be performed.

Effects of wall calcifications in patient-specific wall stress analyses of abdominal aortic aneurysms.

It is generally acknowledged that rupture of an abdominal aortic aneurysm (AAA) occurs when the stress acting on the wall over the cardiac cycle exceeds the strength of the wall. Peak wall stress computations appear to give a more accurate rupture risk assessment than AAA diameter, which is currently used for a diagnosis. Despite the numerous studies utilizing patient-specific wall stress modeling of AAAs, none investigated the effect of wall calcifications on wall stress. The objective of this study was to evaluate the influence of calcifications on patient-specific finite element stress computations. In addition, we assessed whether the effect of calcifications could be predicted directly from the CT-scans by relating the effect to the amount of calcification present in the AAA wall. For 6 AAAs, the location and extent of calcification was identified from CT-scans. A finite element model was created for each AAA and the areas of calcification were defined node-wise in the mesh of the model. Comparisons are made between maximum principal stress distributions, computed without calcifications and with calcifications with varying material properties. Peak stresses are determined from the stress results and related to a calcification index (CI), a quantification of the amount of calcification in the AAA wall. At calcification sites, local stresses increased, leading to a peak stress increase of 22% in the most severe case. Our results displayed a weak correlation between the CI and the increase in peak stress. Additionally, the results showed a marked influence of the calcification elastic modulus on computed stresses. Inclusion of calcifications in finite element analysis of AAAs resulted in a marked alteration of the stress distributions and should therefore be included in rupture risk assessment. The results also suggest that the location and shape of the calcified regions--not only the relative amount--are considerations that influence the effect on AAA wall stress. The dependency of the effect of the wall stress on the calcification elastic modulus points out the importance of determination of the material properties of calcified AAA wall.

Biomarkers of AAA progression. Part 1: extracellular matrix degeneration

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individuals risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase–α1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin–antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.

The mechanical role of thrombus on the growth rate of an abdominal aortic aneurysm

OBJECTIVES In the decision for surgical repair of abdominal aortic aneurysms (AAAs), the maximum diameter is the main factor. Several studies have concluded that the diameter may not be reliable as rupture risk criterion for the individual patient and wall stress was found to have a higher sensitivity and specificity. The AAA wall stress may also be an influential factor in growth of the AAA. This study investigates the effect of intraluminal thrombus on the wall stress and growth rate of aneurysms, using both idealized and patient-specific AAA models in wall stress computations. METHODS Idealized AAA models were created for wall stress analysis. Thrombus was modeled as an incompressible linear elastic material and was fixed to the wall. The reduction in wall stress for a range of thrombus volumes and shear moduli was computed. For 30 patient-specific AAA models with varying thrombus volumes, the wall stress was computed with and without thrombus. The diameter growth rate was compared for AAAs with a small and large thrombus volume. The results were compared between the idealized and patient-specific models. RESULTS The thrombus caused a reduction in wall stress, which was stronger for larger thrombi and higher elastic moduli. Any AAAs with a large thrombus were found to have significant stronger growth in diameter than aneurysms with a small thrombus (P < .01). The stress reduction due to the thrombus showed the same trend for the idealized and patient-specific models, although the effect was overestimated by the idealized models and a considerable variation between patients was observed. CONCLUSION A larger thrombus in AAA was associated with a higher AAA growth rate, but also with a lower wall stress. Therefore, weakening of the AAA wall, under the influence of thrombus, may play a more imminent role in the process of AAA growth than the stress acting on the wall.

In vivo detection of hemorrhage in human atherosclerotic plaques with magnetic resonance imaging

To investigate the performance of high‐resolution T1‐weighted (T1w) turbo field echo (TFE) magnetic resonance imaging (MRI) for the identification of the high‐risk component intraplaque hemorrhage, which is described in the literature as a troublesome component to detect.

Biomarkers of abdominal aortic aneurysm progression. Part 2: inflammation

Defining progression of abdominal aortic aneurysm (AAA) is complicated by several factors, including measurement error, duration of follow-up, and the imaging modality used to assess AAA expansion. Investigations of biomarkers of AAA progression should be standardized so that valid comparisons can be made. Previous research has shown some promising advances towards identifying a reliable and individual predictor of AAA progression. In this second part of our Review on biomarkers of AAA progression, we examine direct and indirect markers of inflammation including various cytokines, C-reactive protein, activators of tissue plasminogen activator and urokinase plasminogen activator, and osteopontin.

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.

Periprosthetic tissue reactions observed at revision of total intervertebral disc arthroplasty

Wear, wear particle induced inflammation, and osteolysis following total disc arthroplasty were, until recently, not thought to be present due to limited intervertebral motion and the lack of a synovial membrane between the lower lumbar vertebrae. The purpose of this study was to evaluate the periprosthetic tissue reactions associated with total disc arthroplasty revision surgery. Periprosthetic samples of fibrous tissue were collected in all patients during revision surgery of SB Charité III disc prostheses. Revision was indicated for intractable pain after an average of 8 years. Histological evaluation was performed in tissue samples of 16 patients using light microscopy and polarized light microscopy with a magnification of 100x. Polyethylene particles were detected in 15 of 16 patients. The smallest particles were the most numerate. A positive correlation was present between the number of particles per mm(2) and the extent of the chronic inflammatory reaction in the periprosthetic fibrous tissue. Osteolysis was observed in one patient. In the tissue samples containing polyethylene particles, TNF-alpha and IL-6 were determined by immunohistochemistry. TNF-alpha and IL-6 were co-expressed as a subset of mononuclear macrophages and giant cells.