Aortic Wall Stress Research Articles

Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta

The human ascending aorta becomes markedly prone to rupture and dissection at a diameter of 6 cm. The mechanical substrate for this malignant behavior is unknown. This investigation applied engineering analysis to human ascending aortic aneurysms and compared their structural characteristics with those of normal aortas. We measured the mechanical characteristics of the aorta by direct epiaortic echocardiography at the time of surgery in 33 patients with ascending aortic aneurysm undergoing aortic replacement and in 20 control patients with normal aortas undergoing coronary artery bypass grafting. Six parameters were measured in all patients: aortic diameter in systole and diastole, aortic wall thickness in systole and diastole, and blood pressure in systole and diastole. These were used to calculate mechanical characteristics of the aorta from standard equations. Aortic distensibility reflects the elastic qualities of the aorta. Aortic wall stress reflects the disrupting force experienced within the aortic wall. Incremental elastic modulus indicates loss of elasticity reserve. Aortic distensibility falls to extremely low levels as aortic dimension rises toward 6 cm (3.02 mm Hg(-1) for small aortas versus 1.45 mm Hg(-1) for aortas larger than 5 cm, P < .05). Aortic wall stress rises to 157.8 kPa for the aneurysmal aorta, compared with 92.5 kPa for normal aortas. For 6-cm aortas at pressures of 200 mm Hg or more, wall stress rises to 857 kPa, nearly exceeding the known maximal tensile strength of human aneurysmal aortic wall. Incremental elastic modulus deteriorates (1.93 +/- 0.88 MPa vs 1.18 +/- 0.21 MPa, P < .05) in aneurysmal aortas relative to that in normal aortas. The mechanical properties of the aneurysmal aorta deteriorate dramatically as the aorta enlarges, reaching critical levels associated with rupture by a diameter of 6 cm. This mechanical deterioration provides an explanation in engineering terms for the malignant clinical behavior (rupture and dissection) of the aorta at these dimensions. This work adds to our fundamental understanding of the biology of aortic aneurysms and promises to permit future application of engineering measurements to supplement aneurysm size in clinical decision making in aneurysmal disease.

Increased aortic wall stress in aortic insufficiency: clinical data and computer model☆

The study was aimed at determining which cardiac pathologies are associated with increased longitudinal stress in the aorta and therefore may be responsible for the intimal transverse tears seen in aortic dissections. Aortic root contrast injections were analyzed in 90 cardiac patients to measure the downward motion of the annulus during a cardiac cycle. A finite element model of the pressurized aortic root, arch and supra-aortic vessels was created to assess the influence of the aortic root motion on the aortic wall stress. The axial displacement of the aortic root ranged from 0 to 14 mm. A multivariate analysis showed that aortic insufficiency (AI) grade, hypokinesis of the left ventricle (HKI), and myocardial hypertrophy (HTR) were 3 independent variables which correlated with the axial displacement of the aortic root (DISP), such that ARM (mm)=5.379 (P<0.0001) +1.186 x AI grade (P=0.0016) - 1.611 x HKI (P=0.0078) - 1.399 x HTR (P=0.0355) with R2=0.23. The major finding of the stress analysis was that in the ascending aorta, at approximately 2 cm above the sino-tubular junction, the longitudinal stress due to aortic root motion was 32% higher in patients with AI than in patients without AI, thereby increasing the risk of transverse intimal rupture. Cardiac patients with AI are likely to experience enhanced longitudinal stress in the ascending aorta due to increased aortic root motion. Thus, these patients should be targeted and their aortic root movement monitored because it may be an important risk factor for aortic dissection.

A computational model to predict aortic wall stresses in patients with systolic arterial hypertension

Computational cardiovascular mechanics has allowed scientists to create complex 3D models for the simulation of cardiovascular problems. Mechanical stress plays a crucial role in the function of the cardiovascular system; stress analysis is a useful tool for the understanding of vascular pathophysiology. By using the spiral CT imaging and computational structural analysis, we present a noninvasive method of wall stress analysis in the normal aorta. The aortic segment was extended from the origin of the inferior mesenteric artery to the aortic bifurcation. The length of this segment was 12 cm, while the maximum transverse diameter was 2.075+/-0.129 cm. A 3D aortic model was constructed based on the CT scan images. The aorta was assumed to have a uniform wall thickness of 1.5mm. The generated unstructured grid, which was used for the structural analysis, consisted of 14,440 hexahedral elements. The wall material was assumed to be hyperelastic, homogeneous, isotropic and nearly incompressible (Poisson ratio=0.45). According to experimental studies, the Young modulus of aortic wall was set equal to 4.66 MPa. The shear stress induced by the blood flow was neglected. A finite-element static structural analysis was performed. Three different cases were examined applying constant intraluminal systolic blood pressures of 120, 180 and 240 mmHg, respectively. The von Mises stress distribution and the displacements of the aortic wall were calculated. Peak wall stress for the normal load case of 120 mmHg was 22.5 N/cm2, while the max displacement was 0.44 mm. The case with the intraluminal pressure of 180 mmHg resulted into peak wall stress of 32 N/cm2 with max displacement 0.59 mm, while for 240 mmHg was 40.6N/cm2, max displacement 0.72 mm. The rise in blood pressure caused all stresses to increase. The pattern of stress distribution and the orientation of the stress were similar for all test cases. A quantitative evaluation of the aortic wall stresses under systolic hypertension is presented. The calculated values of peak wall stress are far lower to those of failure strength of healthy aortic wall specimens estimated by ex vivo mechanical testing (121.0 N/cm2). Our values are consistent with prior stress values predicted by experimental studies. The described methodology offers a significant advancement in incorporating biomechanical principles in the clinical assessment of hypertensive patients with normal or aneurysmatic aortas and can be applied in a patient-specific basis in both conditions in order to detect the vulnerable high stressed regions and the resultant risk of aortic dissection or rupture. We hypothesize that this could assist in deciding the timing of surgical intervention, especially in high-risk patients with abdominal aortic aneurysms.

Effects of ascending aorta replacement on aortic root dilatation

Because of an increase of aortic root wall stress, prosthetic replacement of the ascending aorta might be a risk factor for the progressive increase of the aortic root dimension. Aim of the present study was to evaluate the aortic root diameter change and the progression of aortic valve regurgitation late after ascending aorta replacement for different ethiology. Sixty-three late survivors after supracoronary ascending aortic replacement were evaluated. Forty-one patients were operated on for acute aortic dissecting aneurysm (group I) and 22 for chronic atherosclerotic non-dissecting aneurysm (group II). Aortic root diameter and aortic valve regurgitation were assessed echocardiografically after a mean follow-up of 63+/-31 months and were compared with those early after surgery. Seven patients of group I (17%) needed reoperation for aortic root dilatation or dissection. Twenty-five percent of the patients (15 of group I and 1 of group II) showed at least a 10% increase in aortic root diameter at follow-up (46.8+/-6.1 vs. 38.1+/-6.1mm, P<0.0001). Aortic root diameter increased almost exclusively in patients operated on for acute dissecting aneurysm. A significant worsening of aortic valve insufficiency with time was evident only in patients operated on for acute dissecting aneurysm with an higher incidence in those with progressive root dilatation. Both the increase of aortic root diameter and the progressive worsening of aortic valve insufficiency seem to justify a more aggressive treatment of the aortic root at the time of surgery for acute aortic dissecting aneurysm but not for chronic atherosclerotic non-dissecting aneurysms.

Stress Characteristics of Non-Axisymmetric Synthetic Abdominal Aortic Aneurysm Models: How Real are They?

Abdominal aortic aneurysms (AAAs) are abnormal aortic dilatations that are prone to rupture, with fatal consequences. Synthetic aneurysm models are being used to assess in vivo stress characteristics of aneurysms before and after surgical reinforcement. This study seeks to assess peak wall stress characteristics in a latex life- like model. A life-like non-axisymmetric latex AAA model, constructed from a 3D computed tomographic reconstruction of a real AAA, was incorporated into a pulsatile flow unit (PFU) to simulate the cardiac output. Strain gauges were placed at the neck (n= 2 x 3), inflection point (the junction of neck and sac, n=4 x 3) and maximum anteroposterior diameter (n=4 x 3). The arterial pressure settings used were 130/90 and 140/100mmHg, termed the low and high setting respectively. Strain readings were obtained at 10Hz over 30 seconds using a data logger. Stress was derived using the relationship between stress and Young’s modulus (E= 5.151872 Nmm-2). Peak wall stresses were statistically analysed over the two pressure settings using ANOVA in Minitab 13. The highest stresses were noted at the inflection point and not at the maximum diameter, as might have been expected. Peak inflection point stress anteriorly measured 394.69 (SD 218.1) x10-4 N/cm2 in the low setting, increasing to 715.39(SD 230.32) in the high setting (p&lt;0.001). Posteriorly, peak wall stress measured as high as 373.61(SD207.24) x10-4 Ncm-2 in the low setting, and increased to 1053.32 (SD 347.01) x10-4 Ncm-2 in the high setting (p&lt;0.001). High posterior stress conforms to in vivo studies. Peak wall stresses were not as high in the sac (range 35.08-204.98 x 10-4 Ncm-2 in the low setting and 54.66- 322.73 x 10-4 Ncm-2 in the high setting). An increase in blood pressure caused an increase only in the anterior and lateral, but not the posterior aspect of the sac (p&lt;0.05). Abdominal aortic wall stress is highest at the inflection point, and is affected by blood pressure, which suggests that it is the area most likely to rupture and is critical to reinforcement of the AAA. These readings are lower than stress noticed in vivo due to the lower E of latex as compared to aneurysmal aorta, which structurally is primarily a multilaminate of elastin and collagen; however, the trends themselves may parallel those that occur in AAAs before and after endovascular or open grafting, and therefore justify artificial stress modelling of AAAs.

A Comparative Study of Aortic Wall Stress Using Finite Element Analysis for Ruptured and Non-ruptured Abdominal Aortic Aneurysms*1

Background. The decision to repair an asymptomatic abdominal aortic aneurysm (AAA) is currently based on diameter (≥5.5 cm) alone. However, aneurysms less than 5.5 cm do rupture while some reach greater than 5.5 cm without rupturing. Hence the need to predict the risk of rupture on an individual patient basis is important. This study aims to calculate and compare wall stress in ruptured and non-ruptured AAA.Methods. The 3D geometries of AAA were derived from CT scans of 27 patients (12 ruptured and 15 non-ruptured). AAA geometry, systolic blood pressure and literature derived material properties, were utilised to calculate wall stress for individual AAA using finite element analysis.Results. Peak wall stress was significantly higher in the ruptured AAA (mean 1.02 MPa) than the non-ruptured AAA (mean 0.62 MPa). In patients with an identifiable site of rupture on CT scan, the area of peak wall stress correlated with rupture site.Conclusions. Peak wall stress can be calculated from routinely performed CT scans and may be a better predictor of risk of rupture than AAA diameter on an individual patient basis.

A Comparative Study of Aortic Wall Stress Using Finite Element Analysis for Ruptured and Non-ruptured Abdominal Aortic Aneurysms

Background. The decision to repair an asymptomatic abdominal aortic aneurysm (AAA) is currently based on diameter (≥5.5 cm) alone. However, aneurysms less than 5.5 cm do rupture while some reach greater than 5.5 cm without rupturing. Hence the need to predict the risk of rupture on an individual patient basis is important. This study aims to calculate and compare wall stress in ruptured and non-ruptured AAA. Methods. The 3D geometries of AAA were derived from CT scans of 27 patients (12 ruptured and 15 non-ruptured). AAA geometry, systolic blood pressure and literature derived material properties, were utilised to calculate wall stress for individual AAA using finite element analysis. Results. Peak wall stress was significantly higher in the ruptured AAA (mean 1.02 MPa) than the non-ruptured AAA (mean 0.62 MPa). In patients with an identifiable site of rupture on CT scan, the area of peak wall stress correlated with rupture site. Conclusions. Peak wall stress can be calculated from routinely performed CT scans and may be a better predictor of risk of rupture than AAA diameter on an individual patient basis.

REDUCED AORTIC WALL STRESS IN DIABETES MELLITUS - A CONTRIBUTOR FOR THE LOW INCIDENCE OF ABDOMINAL AORTIC ANEURYSM?

Reduced aortic wall stress in diabetes mellitus - a contributor for the low incidence of abdominal aortic aneurysm

Role of aortic root motion in the pathogenesis of aortic dissection.

The downward movement of the aortic root during the cardiac cycle may be responsible for producing the circumferential tear observed in aortic dissections. Contrast injections were investigated in 40 cardiac patients, and a finite element model of the aortic root, arch, and branches of the arch was built to assess the influence of aortic root displacement and pressure on the aortic wall stress. The axial displacement of the aortic root ranged from 0 to 14 mm. It was increased in patients with aortic insufficiency (22+/-13% of the sino-tubular junction diameter versus 12+/-9%) and reduced in patients with hypokinesis of the left ventricle (10+/-9% of sino-tubular junction versus 17+/-12%). The largest stress increase due to aortic root displacement was found approximately 2 cm above the sino-tubular junction, where the longitudinal stress increased by 50% to 0.32 Nmm(-2) when 8.9-mm axial displacement was applied in addition to 120-mm Hg luminal pressure. A similar result was observed when the pressure load was increased to 180 mm Hg without axial displacement. Both aortic root displacement and hypertension significantly increase the longitudinal stress in the ascending aorta. For patients with hypertension who are at risk of dissection, aortic root movement may be monitored as an important risk factor.

Effect of Variation in Intraluminal Thrombus Constitutive Properties on Abdominal Aortic Aneurysm Wall Stress

The abdominal aortic aneurysm (AAA) is a degenerating disease for which the end stage is the rupture of the vessel wall. Accurate prediction of the stresses acting on the aneurysm tissue may be used to determine the actual risk of rupture of a specific aneurysm. To accomplish this, a correct constitutive model for the aneurysmal aortic wall and any intraluminal thrombus (ILT) present within it are needed. Our laboratory has previously reported the mechanical properties of ILT. The aim of this work is to investigate the reliability of using population-mean values of ILT constitutive parameters to estimate AAA wall stress distribution. For this, a three-dimensional asymmetric model of an aneurysm including ILT was generated and a parametric study was conducted varying ILT constitutive properties within a physiological range. Results show that the presence of any ILT reduces and redistributes the stresses in the aortic wall markedly. Maximum variation in the peak wall stresses for all the models analyzed was 5%. Adopting a nonhomogeneous ILT did not alter the stress distribution. On the basis of these results, we infer that population mean parameters for ILT material characteristics can be used to reasonably estimate the wall stresses in patient specific aneurysm models.

Noninvasive ultrasound measurements of aortic intima-media thickness: implications for in vivo study of aortic wall stress.

The abdominal aorta (AA) has a predilection for aneurysm formation. An etiologic factor may be underlying aortic wall stress. The purpose of this study was to examine whether the intima-media thickness (IMT) of the AA, as a surrogate to arterial wall thickness, can be measured noninvasively with satisfactory results to calculate circumferential wall stress, and to evaluate regional and gender differences in wall stress. Sixty-five middle-aged healthy subjects were examined with B-mode ultrasound to determine the diameter and IMT in the infrarenal AA, common carotid artery (CCA), common femoral artery (CFA), and popliteal artery (PA). Blood pressure was measured noninvasively in the brachial artery. Wall stress was calculated according to the law of LaPlace. Intraobserver variability for the IMT in the AA showed a coefficient of variation of 11%. IMT was thickest in the AA compared with the CCA, CFA, and PA (P <.001). There was a gender difference in IMT in the CFA (P <.05) and PA (P <.01) but not in the AA. Greater wall stress was found in the AA than in the CCA (P <.001) and PA (P <.001), with men having greater wall stress in all studied arterial regions. Aortic IMT can be satisfactorily studied in vivo with noninvasive B-mode ultrasound. There are gender differences in IMT and wall stress, and the largest wall stress is found in the AA in men, which might be important in aneurysm development.

Peroxisome proliferator ameliorates endothelial dysfunction in a murine model of hyperhomocysteinemia.

To test the hypothesis that endothelial dysfunction in hyperhomocysteinemia was due to increased levels of nitrotyrosine and matrix metalloproteinase (MMP) activity in response to antagonism of peroxisome proliferator-activated receptor-alpha (PPAR-alpha), cystathionine beta-synthase (CBS) -/+ mice were bred, tail tissue was analyzed for genotype by PCR, and tail vein blood was analyzed for homocysteine (Hcy) by spectrofluorometry. To induce PPAR-alpha, mice were administered 8 microg/ml of ciprofibrate (CF) and grouped: 1) wild type (WT), 2) WT + CF, 3) CBS, 4) CBS + CF (n = 6 in each group). In these four groups of mice, plasma Hcy was 3.0 +/- 0.2, 2.5 +/- 1.2, 15.2 +/- 2.6 (P < 0.05 compared with WT), 11.0 +/- 2.9 micromol/l. Mouse urinary protein was 110 +/- 11, 86 +/- 6, 179 +/- 13, 127 +/- 9 microg.day(-1). kg(-1) by Bio-Rad dye binding assay. Aortic nitrotyrosine was 0.099 +/- 0.012, 0.024 +/- 0.004, 0.132 +/- 0.024 (P < 0.01 compared with WT), 0.05 +/- 0.01 (scan unit) by Western analysis. MMP-2 activity was 0.053 +/- 0.010, 0.024 +/- 0.002, 0.039 +/- 0.009, 0.017 +/- 0.006 (scan unit) by zymography. MMP-9 was specifically induced in CBS -/+ mice and inhibited by CF treatment. Systolic blood pressure (SPB) was 90 +/- 2, 88 +/- 16, 104 +/- 8 (P < 0.05 compared with WT), 96 +/- 3 mmHg. Aortic wall stress [(SPB. radius(2)/wall thickness)/2(radius + wall thickness)] was 10.2 +/- 1.9, 9.7 +/- 0.2, 16.6 +/- 0.8 (P < 0.05 compared with WT), 13.1 +/- 2.1 dyn/cm(2). The results suggest that Hcy increased aortic wall stress by increasing nitrotyrosine and MMP-9 activity.

Prosthetic replacement of the aorta is a risk factor for aortic root aneurysm development

Background. Noncompliant prostheses are used in aortic replacement. We hypothesized that this leads to increased distension and wall stress in the aortic root because of the loss of ventriculo arterial coupling. Methods. Pressure relations in the aortic root caused by changes of aortic elasticity simulating prosthetic aortic replacement were tested in a computer model. We then developed an in vitro model using porcine aortas and performed in vivo validation. Results. Findings in vitro and in vivo confirmed the predicted changes of the computer model. Pressure amplitude increased significantly by 17% after prosthetic replacement ( p < 0.01). Pressure-time differential (Dp/dt) and dicrotic notch pressure amplitude both increased significantly. Echocardiography demonstrated systolic aortic root distension with percentage area change increasing in vitro from 28.2% ± 9.7% to 35.9% ± 10% ( p < 0.05) and in vivo from 13.3% ± 3.1% to 24.3% ± 3.1% ( p < 0.0001). Aortic root wall stress increased markedly. Conclusions. Replacement of the aorta with vascular prostheses causes important negative alterations of hemodynamics and increases in wall stress.

Simple geometric characteristics fail to reliably predict abdominal aortic aneurysm wall stresses

Purpose: The treatment of patients with abdominal aortic aneurysms (AAAs) is typically based on the potential for rupture. Current rupture assessments are in turn based on statistics from aggregate populations and are incapable of providing precise risk estimates for individual AAAs. Significant benefit could be realized if rupture potential for individual AAAs could be reliably determined on the basis of simple geometric characteristics or the results of symmetric thin-shell analysis. This study seeks to determine whether it is possible to estimate wall stresses by use of these simple measures. Methods: Linear finite element analysis was used to estimate the distribution of von Mises stresses in a series of homogeneous, isotropic, three-dimensional AAA models subject to static loading and assumed to have zero residual stresses. The magnitude of the peak stress was tabulated for each model along with the following characteristics: aneurysm volume; maximum diameter; maximum radius; maximal wall distention; aspect ratio (ratio of greatest anteroposterior diameter to transverse diameter); local radii of curvature (in both longitudinal and circumferential directions); and maximum symmetric thin-shell stress estimates (on the basis of the meridional contour). The relationship between peak stress and each of the characteristics was assessed by use of Spearman rank correlation coefficients, with values less than 0.95 interpreted as signifying unreliable associations. Results: Peak stresses in the individual models ranged from 1.79 × 106 dyne/cm2 to 15.1 × 106 dyne/cm2. The circumferential and longitudinal radii of curvature were frequently able to predict the locations of high stress, but were unreliable in predicting the magnitude of peak stress. The aspect ratio showed the strongest correlation with peak wall stress (r = 0.88, 95% CI, 0.68-0.96), whereas the other characteristics showed even less correlation. Symmetric thin shell analysis accurately predicted stresses in axially symmetric models, but it was incapable of predicting either the location or magnitude of peak stress in asymmetric models. Conclusions: Simple geometric criteria and symmetric thin shell analyses are unreliable in predicting AAA stresses. Future attempts to estimate wall stress and assess risk of rupture for individual AAAs may require detailed threedimensional modeling. (J Vasc Surg 2001;34:308-15.)

Crescent Sign Origin and the Thrombus-to-Lumen Ratio in Abdominal Aortic Aneurysm

HomeRadiologyVol. 214, No. 2 PreviousNext Letters to the EditorCrescent Sign Origin and the Thrombus-to-Lumen Ratio in Abdominal Aortic AneurysmGeorge P. PillariGeorge P. PillariAuthor AffiliationsDepartment of Vascular and Interventional Radiology, Long Island Jewish Medical Center, 270-05 76th Avenue, New Hyde Park, NY 11040George P. PillariPublished Online:Feb 1 2000https://doi.org/10.1148/radiology.214.2.r00nv35604MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References 1 Gonsalves CF. The hyperattenuating crescent sign. Radiology 1999; 211:37-38. Link, Google Scholar2 Pillari G, Chang JB, Zito J, et al. Computed tomography of abdominal aortic aneurysm: an in vivo pathological report with a note on dynamic predictors. Arch Surg 1988; 123:727-732. Crossref, Medline, Google Scholar3 Mower WR, Quinones WJ, Gambhir SS. Effect of intraluminal thrombus on abdominal aortic aneurysm wall stress. J Vasc Surg 1997; 26:602-608. Crossref, Medline, Google ScholarArticle HistoryPublished in print: Feb 2000 FiguresReferencesRelatedDetailsCited ByCirculation Journal, Vol. 85, No. 12Abdominal Aortic Aneurysms Revisited: MDCT with Multiplanar Reconstructions for Identifying Indicators of Instability in the Pre- and Postoperative PatientAjay D. Wadgaonkar, James H. Black, III, Elizabeth K. Weihe, Stefan L. Zimmerman, Elliot K. Fishman, Pamela T. Johnson, 15 January 2015 | RadioGraphics, Vol. 35, No. 1Journal of Biomechanical Engineering, Vol. 131, No. 6BioMedical Engineering OnLine, Vol. 5, No. 1Recommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 214, No. 2 Metrics Altmetric Score PDF download

Aortic dissection in Marfan’s syndrome

Background. Aortic dissection is the most frequent cause of premature death in Marfan’s syndrome. Low-risk elective surgery of the abnormal aortic root has the potential to prevent this complication. Methods. We examine genetic, structural, and pathophysiological mechanisms of aortic dissection and discuss the surgical methods used when dissection occurs. Results. Abnormal fibrillin disturbs the functional relationship between blood flow and vascular endothelial cell response (mechanotransduction). Decreased arterial distensibility also decreases aortic wall stress, thereby predisposing to dissection in the weakened arterial wall. Radical root and wall surgery and lifelong beta-blockade are required after aortic dissection. Conclusions. Detailed lifelong medical and surgical treatment can greatly prolong life in Marfan’s syndrome. Elective aortic root replacement is paramount in preventing aortic dissection and avoiding subsequent problems in the distal aorta.

Biomechanics of abdominal aortic aneurysm in the presence of endoluminal thrombus: Experimental characterisation and structural static computational analysis

To evaluate the role played by biomechanical and geometrical parameters of endoluminal thrombus and of aortic wall on abdominal aortic aneurysm (AAA) behaviour. Tensile tests on 21 AAA thrombus specimens from six patients undergoing AAA repair and numerical evaluation of aneurysmal aortic wall stress and strain distribution. Parameters of the analysis were lumen eccentricity, thrombus Young's Modulus and the aortic wall constitutive equation. There was a linear stress/strain for all the thrombus specimens. The numerical analyses show the mechanical behaviour of AAA as a function of lumen eccentricity and biomechanical parameters. Well organised thrombus reduces the effect of the pressure load on the aneurysmal aortic wall.

Dose-Related Hemodynamic and Electrocardiographic Effects of the Calcium Promoter BAY y 5959 in the Presence or Absence of Congestive Heart Failure

Objectives. The aim of this study was to assess the cardiovascular effects of BAY y 5959, a calcium promoter modulating myocardial calcium channels, in the presence or absence of congestive heart failure.Background. There is still a clinical need for short-term administration of intravenous positive inotropes. BAY y 5959 was developed as a new approach to increase myocardial performance by selectively enhancing calcium influx in the myocytes.Methods. Forty-one patients (21 without and 20 with congestive heart failure) were studied in an open label, dose-ranging study. Hemodynamic variables (including left ventricular [LV] angiography) and plasma samples were obtained at baseline and after 20 min of intravenous infusion of BAY y 5959 at doses ranging from 0.25 to 4.5 μg/kg body weight per min.Results. In both study groups, BAY y 5959 produced dose-dependent increases in the indexes of inotropic state, without affecting isovolumetric relaxation rate. The magnitude of the response was comparable in patients with or without heart failure (average 38% increase in maximal first derivative of LV pressure [dP/dt max] at plasma levels of 100 μg/liter). BAY y 5959 also induced mild but statistically significant bradycardia and significantly decreased end-systolic volume while producing a leftward shift of the pressure-volume loop. Mean aortic pressure was unaffected at doses up to 3.0 μg/kg per min, and cardiac index improved in patients with heart failure at doses of 2.0 μg/kg per min (+23%, p < 0.05). However, at a dose of 4.5 μg/kg per min, mean aortic pressure and LV systolic wall stress increased, suggesting systemic vasoconstriction. The QT interval was also prolonged significantly at most doses.Conclusions. BAY y 5959 exhibits positive inotropic effects in patients with and without heart failure. The optimal response— combining bradycardia, reduced preload and improved cardiac output—appeared to be achieved at a dose of ∼2.0 μg/kg per min. The impact of QT prolongation with regard to potential antiarrhythmic or proarrhythmic effects is unclear at this time.

Effect of intraluminal thrombus on abdominal aortic aneurysm wall stress.

Abdominal aortic aneurysms (AAAs) rupture when the wall stress exceeds the strength of the vascular tissue. Intraluminal thrombus may absorb tension and reduce AAA wall stress. This study was performed to test the hypothesis that intraluminal thrombus can significantly reduce AAA wall stress. AAA wall stresses were determined by axisymmetric finite element analysis. Model AAAs had external diameters ranging from 2.0 to 4.0 cm. Model parameters included: AAA length, 6 cm; wall thickness, 1.5 mm; Poisson's ratio, 0.49; Young's modulus, 1.0 MPa; and luminal pressure, 1.6 x 10(5) dyne/cm2. Stresses were calculated for each model without thrombus, and then were recalculated with thrombus filling 10% of the AAA cavity. Calculations were repeated as thrombus size was increased in 10% increments and as thrombus elastic modulus increased from 0.01 MPa to 1.0 MPa. Maximum wall stresses were compared between models that had intraluminal thrombus and the unmodified models. Stress reduction greater than 25% was considered significant. The maximum stress reduction of 51% occurred when thrombus with elastic modulus of 1.0 MPa filled the entire AAA cavity. Stresses were reduced by only 25% as modulus decreased to 0.2 MPa. Similarly, decreasing thrombus size by 70% resulted in stress reduction of only 28%. Large AAAs experienced greater stress reduction than small AAAs (48% vs 11%). Intraluminal thrombus can significantly reduce AAA wall stress.

Induction of growth hormone receptor and insulin-like growth factor-I mRNA in aorta and caval vein during hemodynamic challenge.

Induction of two-kidney, one clip hypertension (renal hypertension) is characterized by a slow increase in left ventricular tension and aortic wall stress, as opposed to aortocaval fistula or shunt volume overload, which induces a marked and rapid onset of wall stress in the caval vein and right ventricle. In the present study, we applied hemodynamic challenge to study the growth response involving gene expression of insulin-like growth factor-I (IGF-I) and growth hormone receptor (GH-R) mRNA in aorta and caval vein. Volume overload and pressure overload were induced in Wistar rats by means of shunt and renal hypertension, respectively. Systolic pressure was measured before excision of the great vessels, which was performed between 2 and 12 days postoperatively. Aortic and caval vein IGF-I and GH-R mRNA expressions were measured by means of a solution hybridization assay, and the caval vein was analyzed for IGF-I protein by immunohistochemistry. In the volume-distended but not pressurized caval vein in shunt rats, verified by telemetry recordings, there was an eightfold increase in IGF-I and 3.5-fold increase in GH-R mRNA at day 4 versus control. The IGF-I protein appeared to be localized in smooth muscle cells. In the aorta of the renal hypertension group, changes were of a slower onset. At day 7, there was a fourfold increase in IGF-I and five-fold increase of GH-R mRNA expressions versus sham-operated rats. Both the shunt caval vein and renal hypertension aorta showed evidence of a structural adaptation of the growth response. The present study suggests that acute elevation in vascular wall stress is an important triggering factor for overexpression of IGF-I and GH-R mRNA in great vessels. The growth hormone/insulin-like growth factor axis may be an important link in mediating structurally adaptive growth responses in the blood vessel wall.