Transport of Low-Density Lipoprotein Into the Blood Vessel Wall During Atherogenic Diet in the Isolated Rabbit Carotid Artery.

BACKGROUND: Atherosclerosis is a chronic fibroproliferative disease that includes accumulation of cholesterol-rich lipids in the arterial wall. Though numerous studies have investigated atherosclerosis, not enough is known about the exact mechanisms of low-density lipoprotein (LDL) transport into the blood vessel wall. Therefore, we explored the (125)I-LDL transport into the arterial wall under constant perfusion flow and pressure as well as the influence of duration of atherogenic diet on (125)I-LDL transport and biomechanical properties of carotid artery. METHODS AND RESULTS: The isolated segment of rabbit carotid artery was used under constant perfusion flow and pressure-induced (0 mmHg and 140 mmHg) blood vessel distension, with the possibility to change and precisely calculate shear stress during the experiment. Obtained results indicate the influence of atherogenic diet duration and consequent variation of shear stress on (125)I-LDL transport into the blood vessel wall. (125)I-LDL transport into the blood vessel wall at low pressure-induced blood vessel distension decreases by the increase of the shear stress and in relation to the atherogenic diet duration. At high pressure-induced blood vessel distension, (125)I-LDL transport increases in relation to the atherogenic diet duration and the increase of shear stress. CONCLUSIONS: The influence of shear stress is a more dominant parameter on LDL uptake at low pressure-induced blood vessel distension; however, the atherogenic diet duration has more of a dominant influence on LDL uptake at high pressure-induced vessel distension.

Hyperelastic behavior of porcine aorta segment under extension-inflation tests fitted with various phenomenological models.

Most of hyperelastic models for the constitutive modeling of the typical mechanical behaviour of the arterial wall tissue in literature are based on the test data from different animals and arteries. This paper is concerned with the material parameter identification of several phenomenological hyperelastic models by fitting the data from five extension-inflation tests of the porcine aorta segment, carried out in our laboratory. A membrane approximation is used to compute stresses and strains achieved during experiments, with usual assumption of material incompressibility. Three orthotropic two-dimensional strain-energy functions, based on use of the Green-Lagrange strains, are fitted to the test data: the well-known Fung's exponential model; the classical polynomial model with seven constants; and the logarithmic model; and also, two three-dimensional models are employed: polyconvex anisotropic exponential hyperelastic model and the convex isotropic exponential rubber-like hyperelastic constitutive law depending on the first invariant of the right Cauchy-Green deformation tensor. It has been found that isotropic model overestimates values of stresses in axial, and underestimates values of stresses in circumferential direction of artery segment, due to pronounced tissue anisotropy. Also, all two-dimensional models considered give good and similar prediction, while the polyconvex model demonstrates slightly lower performance in the axial direction of artery.

Glucagon effects on 3H-histamine uptake by the isolated guinea-pig heart during anaphylaxis.

We estimated the influence of acute glucagon applications on (3)H-histamine uptake by the isolated guinea-pig heart, during a single (3)H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 (-), and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change (3)H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, (3)H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of (3)H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9-7.38 × 10(-8) µM) is significantly lower than the histamine level in the absence of glucagon (10.35-10.45 × 10(-8) µM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 (-) level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

ARTreat Project: three-dimensional numerical simulation of plaque formation and development in the arteries.

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprotein (LDL) transport in lumen of the vessel is coupled with Kedem-Katchalsky equations. The inflammatory process was solved using three additional reaction-diffusion partial differential equations. Transport of labeled LDL was fitted with our experiment on the rabbit animal model. Matching with histological data for LDL localization was achieved. Also, 3-D model of the straight artery with initial mild constriction of 30% plaque for formation and development is presented.

The mathematical analysis of the heart rate and blood lactate curves during incremental exercise testing.

This paper describes a new mathematical approach for the analysis of HR (heart rate) and BL (blood lactate) curves during incremental exercise testing using a HR/BL curve and its derivatives, taking into account the native shape of all curves, without any linear approximation. Using this approach the results indicate the appearance of three characteristic points (A, B and C) on the HR/BL curve. The point A on the HR/BL curve which is the value that corresponds to the load (12.73 ± 0.46 km h-1) at which BL starts to increase above the resting levels (0.9 ± 0.06 mM), and is analogous to Lactate Turn Point 1 (LTP1). The point C on the HR/BL curve which corresponds to a BL of approximately 4mM, and is analogous to LTP2. The point B on the HR/BL curve, which corresponds to the load (16.32 ± 0.49 km h-1) at which the moderate increase turns into a more pronounced increase in BL. This point has not been previously recognized in literature. We speculate this point represents attenuation of left ventricular ejection fraction (LVEF) increase, accompanied by the decrease in diastolic time duration during incremental exercise testing. Proposed mathematical approach allows precise determination of lactate turnpoints during incremental exercise testing.

Histamine blood concentration in ischemic heart disease patients.

The aim of this study was to investigate histamine blood concentration in subjects suffering from different types of ischemic heart diseases during the period of eight days. Our results showed that the histamine blood level was associated with different types of ischemic heart diseases. The blood histamine level in all investigated patients was significantly higher when compared to control subjects (44.87 ± 1.09 ng mL(-1)), indicating the increase of histamine release in patients suffering from coronary diseases. In patients suffering from ACS-UA and ACS-STEMI, the second day peak of histamine level occurs (90.85 ± 6.34 ng mL(-1) and 121.7 ± 6.34 ng mL(-1), resp.) probably as the reperfusion event. Furthermore, our data suggest that histamine can be additional parameter of myocardial ischemia along with cardiac specific enzymes and may prove to be an excellent single prognostic marker for multitude of ischemic heart diseases.

Mathematical analysis of the heart rate performance curve during incremental exercise testing.

In this study we performed laboratory treadmill protocols of increasing load. Heart rate was continuously recorded and blood lactate concentration was measured for determination of lactate threshold by means of LTD-max and LT4.0 methods.Our results indicate that the shape of heart rate performance curve (HRPC) during incremental testing depends on the applied exercise protocol (change of initial speed and the step of running speed increase, with the constant stage duration). Depending on the applied protocol, the HRPC can be described by linear, polynomial (S-shaped), and exponential mathematical expression.We presented mathematical procedure for estimation of heart rate threshold points at the level of LTD-max and LT4.0, by means of exponential curve and its relative deflection from the initial trend line (tangent line to exponential curve at the point of starting heart rate). The relative deflection of exponential curve from the initial trend line at the level of LTD-max and/or LT4.0 can be defined, based on the slope of the initial trend line. Using originally developed software that allows mathematical analysis of heart rate-load relation, LTD-max and/or LT4.0 can be estimated without direct measurement of blood lactate concentration.

Computer simulation and experimental analysis of LDL transport in the arteries.

Atherosclerosis develops from oxidized low-density lipoprotein molecules (LDL). When oxidized LDL evolves in plaque formations within an artery wall, a series of reactions occur to repair the damage to the artery wall caused by oxidized LDL. Macrophages accumulate inside arterial intima, they started to collect oxidized LDL and form foam cells. Smooth muscle cells accumulate in the atherosclerotic arterial intima, where they proliferate and secrete extracellular matrix to form a fibrous cap. In this study, experimental model of LDL transport on the isolated blood vessel from rabbit on high fat diet after 8 weeks is simulated numerically by using a specific model and histological data. The 3D blood flow is governed by the Navier-Stokes equations, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow by the convection-diffusion equation. LDL transport in lumen of the vessel is described by Kedem-Katchalsky equations. The inflammatory process is solved using three additional reaction-diffusion partial differential equations. Matching of histological rabbit data is performed using 3D histological image reconstruction and 3D deformation of elastic body. Computed concentrations of labeled LDL of 5.2 % and macrophages distribution of 4.2% inside the media are found to be in good agreement with experimental results. This simulation study provides a useful tool for understanding and prediction of LDL transport through the arterial wall and evolution of atherosclerotic plaques.

Histamine index and clinical expression of rheumatoid arthritis activity.

BACKGROUND/AIM: Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. METHODS: Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. RESULTS: Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significiant difference in the histamine index which was increased proportionally with disease activity. CONCLUSION: Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.

Influence of admission plasma glucose level on short- and long-term prognosis in patients with ST-segment elevation myocardial infarction.

BACKGROUND/AIM: Hyperglicemia is common in patients with ST-elevation myocardial infarction (STEMI) and is associated with high risk of mortality and morbidity. Relationship between admission plasma glucose (APG) levels and mortality in diabetic and nondiabetic patients with STEMI needs further investigation. The aim of this study was to analyse the short- and long-term prognostic significance of APG levels in patients with STEMI with and without diabetes. METHODS: This study included 115 patients with STEMI, 86 (74.8%) nondiabetic and 29 (25.2%) dibaetic patients, in which we performed a prospective analysis of the relationship between APG levels and short- and long-term mortality. RESULTS: Comparison of APG levels between nondiabetic (8.32 +/- 2.4 mmol/L) and diabetic (10.09 +/- 2.5 mmol/L) patients showed statistically significantly higher average APG levels in diabetic patients (p = 0.001). In all patients observed who died either after one month or one year after STEMI, average APG values were significantly higher in comparison with those in survived patients. There was no statistical significance in average APG levels in the diabetic patients with STEMI who died after one month and those who survived (10.09 +/- 2.68 vs 10.0 +/- 2.51 mmol/L, respectively; p = 0.657), as well as those who died after one year and those who survived (10.1 +/- 1.92 vs 10.09 +/- 2.8 mmol/L, respectively; p = 0.996). There was, however, statistical significance in average APG levels in the nondiabetic patients with STEMI who died after one month and those who survived (9.97 +/- 2.97 vs 7.91 +/- 2.08 mmol/L, respectively; p = 0.001), as well as those who died after one year and those who survived (9.17 +/- 2.49 vs 7.84 +/- 2.24 mmol/L, respectively; p = 0.013). CONCLUSION: Acute hyperglicemia in the settings of STEMI worsenes the prognosis in patients with and without diabetes. Our study showed that nondiabetic patients with high APG levels are at higher risk of mortality than patients with a known history of diabetes.

Glucagon effects on ischemic vasodilatation in the isolated rat heart.

The myocardial reperfusion following ischemia leads to the ischemic vasodilation by affecting the release of various vasoactive substances, such as free radicals, NO, and histamine. In addition, some evidences suggest that glucagon itself may alter the release of those substances. In this study, we investigated the ischemic vasodilation of the isolated rat heart, as well as the concentrations of NO, TBARS, and histamine in the coronary venous effluent either in the presence or in the absence of glucagon. Our results showed that in the presence of glucagon, there was a faster restoration of coronary perfusion pressure during ischemic vasodilation compared to the absence of glucagon (124 +/- 5.6 versus 81 +/- 5.2 s) with no apparent changes in TBARS concentration. The glucagon's administration leads to the decreased release of histamine by approximately 35%. Biphasic release of NO in the presence of glucagon initially showed augmentation by 60%, followed by the significant attenuation of 45%.

The new experimental model for behavioral investigations in animal studies.

In this paper a video file based approach to evaluate position and locomotion in animal behavior experiments is described. For this purpose original software Animal Tracker for transforming a video data to a log file which is suitable for further computational analyzes, was developed. To perform analyzes from the log file, an additional software PostProc), which enables assessment of locomotion, velocity or place preferences, was created. For video recording software called DScaler was used. This is an open source software and freely available for download. The method that we describe in this paper is based on simple video equipment and supported by three software mentioned above. This method enables performing of a wide diversity of experimental designs without limitations in time duration, color and light conditions, shape and size of experimental area and/or investigated objects. As an example, results obtained from experiments with rats in an Open-field test are included. One group of animals was treated with benzodiazepine (2 mg.kg(-1), single dose, subcutaneously). This easy to use system can be implemented in most laboratories without any special training and used by investigators in the field of animal behavior research.

Dynamic response of blood vessel in acute renal failure.

In this study we postulated that during acute renal failure induced by gentamicin the transient or dynamic response of blood vessels could be affected, and that antioxidants can prevent the changes in dynamic responses of blood vessels. The new approach to ex vivo blood vessel experiments in which not only the end points of vessels response within the time interval is considered, but also dynamics of this response, was used in this paper. Our results confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals. The beneficial effects of vitamin C administration to gentamicin-treated animals are also confirmed through: lower level of blood urea and creatinine and higher level of potassium. The pressure dynamic responses of isolated blood vessels show a faster pressure change in gentamicin-treated animals (8.07 +/- 1.7 s vs. 5.64 +/- 0.18 s). Vitamin C administration induced slowdown of pressure change back to the control values. The pressure dynamic properties, quantitatively defined by comparative pressure dynamic and total pressure dynamic, confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals and beneficial effects of vitamin C administration.

Computer simulation of flow and mixing at the duodenal stump after gastric resection.

AIM: To investigate the flow and mixing at the duodenal stump after gastric resection, a computer simulation was implemented. METHODS: Using the finite element method, two different Billroth II procedure cases (A and B) were modeled. Case A was defined with a shorter and almost straight duodenal section, while case B has a much longer and curved duodenal section. Velocity, pressure and food concentration distribution were determined and the numerical results were compared with experimental observations. RESULTS: The pressure distribution obtained by numerical simulation was in the range of the recorded experimental results. Case A had a more favorable pressure distribution in comparison with case B. However, case B had better performance in terms of food transport because of more continual food distribution, as well as better emptying of the duodenal section. CONCLUSION: This study offers insight into the transport process within the duodenal stump section after surgical intervention, which can be useful for future patient-specific predictions of a surgical outcome.

Evaluation of dynamic response and biomechanical properties of isolated blood vessels.

In this study we present the experimental and mathematical model for a precise assessment of isolated blood vessels dynamic response under a sudden change of blood pressure. Only the end points within the time interval of the considered dynamic response of the blood vessel, or so-called "alternate steady states" of the processes, were usually considered in various studies. These studies do not provide an insight how the process variables change between these alternate steady states. Isolated blood vessels (rat abdominal aorta) were used to determine how the process dynamics can be described in detailed quantitative terms by mathematical parameters. The experimental model and mathematical procedures presented in this study describe precisely (at a high sensitivity level) the time history of the pressure and the diameter change in between alternate steady states, when an abrupt change of blood pressure occurs at the vessel outlet. Also, the experimental model and mathematical procedures were used to determine changes in the stress-strain law, caused by the action of L-arginine. The presented experimental design and mathematical model can be used for assessment of isolated blood vessel dynamic responses under different stimuli, such as drug effects, electrostimulation etc.