Suzana Pantovic

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.

Kinetics of Thyroxine (T4) and Triiodothyronine (T3) Transport in the Isolated Rat Heart

The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of 125I‐thyroxine (125I‐T4) and 125I‐triiodothyronine (125I‐T3) from the extracellular space into heart cells was measured relative to the extracellular space marker 3H‐mannitol. The thyroid hormone maximal uptake was 54.4% for 125I‐T4 and 52.15% for 125I‐T3. The thyroid hormone net uptake was 25.69% for 125I‐T4 and 25.49% for 125I‐T3. Backflux from the intracellular space was 53.17% for 125I‐T4 and 61.59% for 125I‐T3. In the presence of unlabelled thyroid hormones, 125I‐T4 and 125I‐T3 maximal uptakes were reduced from 10.1 to 59.74% and from 34.6 to 65.3%, respectively, depending on the concentration of the unlabelled hormone, suggesting a saturable mechanism of the thyroid hormone uptake by the heart cells, with Km(T4)= 105.46 μM and the maximal rate of 125I‐thyroid hormone flux from the extracellular space to heart cells (Vmax(T4)) = 177.84 nM min−1 for 125I‐T4 uptake, and Km(T3)= 80.0 μM and Vmax(T3)= 118.5 nM min−1 for 125I‐T3 uptake.

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 glucagons 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%.

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.

Glucagon Effects on 3H-Histamine Uptake by the Isolated Guinea-Pig Heart during Anaphylaxis

We estimated the influence of acute glucagon applications on 3H-histamine uptake by the isolated guinea-pig heart, during a single 3H-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 3H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, 3H-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 3H-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.

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.

Modeling of abdominal aortic aneurism rupture by using experimental bubble inflation test

Aneurysm rupture is a biomechanical phenomenon that occurs when the mechanical stress acting on the inner wall exceeds the failure strength of the diseased aortic tissue. Besides numerous advantages in surgical and anaesthesiological management, emergency procedure leads to fatal outcome in 20-50% of those who reach hospital. Prediction of influence of dynamic blood flow on natural history of aneurysmatic disease and outcome of therapeutic procedures could contribute to treatment strategy and results. In this study we presented experimental design for estimation of the material property of real human aorta tissue from bubble inflation test. Then we investigated fluid-structure interaction of pulsatile blood flow in the specific patient three-dimensional model of abdominal aortic aneurysms (AAAs). Numerical predictions of blood flow patterns and nonlinear wall stresses in AAAs are performed in compliant wall anisotropic model using the finite element method. These computational procedures together with experimental determination of the nonlinear material property could provide us more accurate assessment of aneurysm rupture risk.

A five-compartment biokinetic model for 90Y-DOTATOC therapy

PURPOSE Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide targeted therapy using somatostatin receptor-binding peptides such as 90 Y- and 177 Lu-DOTATOC. The objective of this work was to develop a biokinetics model of 90 Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses in kidney and tumor. METHODS A multi-compartment model described by two sets of differential equations, one set for the actual 30-min infusion and the other set for the post-infusion period was developed and activities were measured by liquid scintillation counting in blood (compartment 1) and the urine (compartment 3). The inter-compartment transfer coefficients, λij , were varied to yield the best fit of the calculated to the measured time-activity data and the 90 Y-DOTATOC time-activity data in the five-compartments comprising the human body were thus determined. The resulting time-activity curves were integrated over the interval from 0 to 72 h post administration to obtain the number of radioactive decays in each compartment and, in case of the kidneys and tumor, then multiplied by the self-dose 90 Y beta particle absorbed fraction, determined by Monte Carlo (MC) simulation, the kidney and tumor absorbed doses. RESULTS Transfer coefficients λij , were determined for five-compartments for all patients. Time- activity curves of 90 Y-DOTATOC in 14 patients were determined, and two typical ones are shown graphically. Absorbed doses in the tumor and kidneys, obtained by the developed method, were determined. The mean absorbed dose in a kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73-2.42 mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05-42.31 mGy/MBq). CONCLUSION Analytical solution of a biokinetic model for 90 Y-DOTATOC therapy enabled determination of the transfer coefficients and derivation of time-activity curves and kidney and tumor absorbed doses for 14 treated patients. The model can be applied to other radionuclides where elimination is predominantly through urine, which is often the case in radiopharmaceuticals.

Manufacturing of Biodegradable Scaffolds to Engineer Artificial Blood Vessel

Abstract Blood vessels diseases such as cardiac infarction with coronary artery occlusion, peripheral arterial disorders, or stroke of carotid or cerebral arteries, are the leading causes of death in the world. One of medical procedures for clinical treatment of vascular diseases is the blood vessels grafting. As the autologous blood vessels, which are the “golden standard” for coronary grafting, are not always suitable for blood vessels grafting, there is a need to develop artificial blood vessels as a vascular prostheses, either from natural and synthetic materials, permanent synthetic or biodegradable scaffolds which would be suitable for vascular grafts. Considering this to be our study goal we made bilayered biodegradable polycaprolactone scaffolds with different properties and evaluated their morphological and biomechanical characteristics.

COMPARTMENT BIOKINETIC MODEL FOR 90Y-DOTATOC

Biokinetic of 90Y-DOTATOC in human body during treatment of neuroendocrine and medullary thyroid tumors is described in this work. For this purpose, the human body may be represented by 4 compartments: blood, kidneys, urinary bladder and tumor. System of differential equations was developed, whose solution is presented in this paper. The aim is the determination of transfer coefficients between individual compartments for a better estimation of the dose in the tumor and other organs of the human body. A computer program is written in standard Fortran90 programming language.