Perfusion Rate Research Articles

Dynamic Contrast Enhanced (DCE) MRI-Derived Renal Perfusion and Filtration: Experimental Protocol.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide a noninvasive way for assessing renal functional information following the administration of a small molecular weight gadolinium-based contrast agent. This method may be useful for investigating renal perfusion and glomerular filtration rates of rodents in vivo under various experimental (patho)physiological conditions. Here we describe a step-by-step protocol for DCE-MRI studies in small animals providing practical notes on acquisition parameters, sequences, T1 mapping approaches and procedures.This chapters is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

Mathematical modeling of temperature variation in breast tissue with and without tumor/cyst during menstrual cycle

The thermoregulation of human female body is influenced by hormonal and physiological changes in the body during the menstrual cycle. The fluctuation of estrogen and progesterone hormones, release in the follicular phase and the luteal phase of menstrual cycle, respectively play an important role in the growth of breast ducts and lobules (milk glands). The imbalance of these hormones causes breast tumors/cysts. The body core temperature, blood perfusion and metabolism rate are higher in the luteal phase than the follicular phase of menstrual cycle. In the present work, a tumor/cyst is assumed to be in the glandular layer. A two-dimensional Pennes bioheat equation is solved to find the temperature variation in breast tissue with and without tumor/cyst during the menstrual cycle by using the finite element method. The results show that the temperature of each layer of breast tissue in the luteal phase is higher than the follicular phase in the case of normal breast, tumorous breast and breast with cyst.

NUMERICAL ANALYSIS OF NON-FOURIER PHASE-CHANGE HEAT TRANSFER IN BIOLOGICAL TISSUES WITH THE ADDITION OF NANOPARTICLES

An improved cryopreservation method is the need of the hour in the medical field to control the freezing rate to prevent the damage of biological tissues. The present article addresses two issues. First, a numerical model is developed for cryopreservation of biological tissues where non-Fourier heat conduction plays an important role in predicting the freezing rate. A new version of enthalpy method is then proposed and applied for capturing the freezing front. Secondly, with the addition of MgO nanoparticles, which are biodegradable, biocompatible, and nontoxic, the enhancement of freezing rate is explored. The temperature field at different points in the domain is studied. The effect of the different volume fraction of nanoparticles on the freezing rate is discussed in detail. It is observed that the blood perfusion rate has a significant role in predicting the freezing rate.

Fabrication of cyclic olefin polymer and polydimethylsiloxane co-bonded microfluidic device and its appliactions in terahertz biological effects on intestinal cells

<sec>The current research on the terahertz biological effects at a cellular level is limited by the conventional petri dishes used for cell culture, which cannot be directly used for confocal laser microscopy. In this research, the cycloolefin polymer (COP), a material that possesses low terahertz absorption rate but excellent optical property for microscopy, is bonded to polydimethylsiloxane (PDMS), thereby developing a novel COP-PDMS microfluidic device by using the techniques of soft etching, photolithography, plasma cleaning, high-temperature and high-pressure incubation. The bonding strength of resulting device is tested by using a push-tension meter. The results indicate that the developed device shows a bonding strength as strong as the device fabricated by quartz and PDMS, which is thought as the tightest binding in the multiple types of microfluidic device. In addition, by perfusing the device chamber at a high flow rate (200 μL/s) and long-term time-course (2 weeks), which simulates the dynamic shearing stress occurring in <i>in-vivo</i> organs and tissues, this COP-PDMS microfluidic device can still maintain the original shape and sealing property, indicating that this device qualifies the requirements of the following dynamic cell culture.</sec><sec>The biological effects of terahertz on the cells are explored by using this COP-PDMS microfluidic device mentioned above. In this device, we develop the dynamic culture of intestinal epithelial cells Caco-2 with a perfusion rate of 0.05 μL/s, which meets the findings of the <i>in-vivo</i> gastrointestinal lumen shearing stress. The Caco-2 cells are then irradiated with 0.1 THz wave with the power of 15 mW/cm<sup>2</sup> for 3 days, and the irradiation duration is 10 min per day. The biological effects of terahertz irradiation on the intercellular tight junction protein ZO-1, the Paxillin relating to the cell adhesion and migration, and the cytoskeletal microfilament protein F-actin of Caco-2 cells are detected in the device directly using the technique of immunofluorescence staining.</sec><sec>The results show that the morphology of cell adhesion as well as the level and distribution of ZO-1 and Paxillin are changed. In brief, the protein expression of ZO-1 and Paxillin are induced more by the terahertz irradiation, while the F-actin is not influenced by the irradiation. As can be seen from the F-actin results, the cells without terahertz irradiation show a spread and outward shape with regular smooth cell edge while a contraction and burr shape of cell edge are shown after irradiation, suggesting that the cell adhesion is weakened after irradiation. Even though the expression level of F-actin is consistent, the changed morphology indicates that terahertz may regulate the interaction and aggregation among actin proteins in cells. Interestingly, the ZO-1 presents diffuse distribution in the cells and its location on the cell membrane is not obvious, that is, a large amount of ZO-1 expresses not only on the cell membrane but also in the intracellular matrix after the irradiation. The expression of Paxillin is enhanced after terahertz irradiation, and some cells show local aggregation and distribution of Paxillin. These indicate that the terahertz irradiation might affect the biomolecular mechanism of synthesis and distribution of protein. The COP-PDMS co-bonded microfluidic device developed in this study provides a convenient and effective platform for exploring the biological effects of terahertz irradiation on cells, and is expected to be further used for real-time research on the effects of terahertz on cells and molecules in the future.</sec>

Evaluation of the suitability of a donor heart for transplantation after various asystole periods in experiment

The lack of donor hearts for transplantation in patients with end-stage chronic heart failure makes us look for new ways to increase the pool of donors. One of the possible ways to increase the donor base may be the use of asystolic donors, i. e. patients with in-hospital cardiac arrest or patients with cardiac arrest after brain death. The aim of the study was to examine the morphofunctional state of the heart after various periods of normothermic asystole in an experiment on rats. Materials and methods . Experiments were performed on female Wistar rats. After cervical dislocation and registration of respiratory arrest, the body temperature of the rat was maintained above at 36.5±0.5 °C for 10, 15 and 20 minutes, depending on the group. After asystole period, the heart was connected to the Langendorff apparatus to provide perfusion for 90 minutes. During perfusion of the heart, the pulse pressure inside the left ventricle (LVPP) and the volumetric flow rate of coronary perfusion (CP) were recorded every 15 minutes. After the end of the experiment, the volume of necrosis was calculated. Results . In the group with 20-minute ischemia, there was no recovery of ventricular contractions, the volume of necrosis was 34,9±11,7 %. In the group with 15-minute ischemia, the volume of necrosis was 19,5±7,6 %. In the group with 10-minute normothermic ischemia, the volume of necrosis was 13,1±5,1 %. Conclusions . 15 minutes of normothermic cardiac arrest in situ causes irreversible damage to the heart of the animal, which does not allow us to consider it as a potential donor heart. However, this volume of damage to the myocardium and microvasculature, together with the restoration of the contractile activity of the heart, makes this group the main one for the continuation of such experiments using various methods of heart reconditioning.

Mechanisms of ischemic skeletal muscle regeneration mediated by mechanically constrained human allogeneic mesenchymal stromal cells

Background and Hypothesis: Critical limb threatening ischemia (CLTI) is the end stage of peripheral arterial disease (PAD). CLTI presents a significant risk for lower extremity amputation, especially in diabetic patients with poor options for revascularization. Additionally, using a novel diabetic mouse model of CLTI, we have shown that IM injection of 3D cultured MSCs (spheroids) is more effective in promoting skeletal muscle regeneration of ischemic muscle than monolayer cultured MSC. We hypothesize that this result is due to the mechanical constrained nature of the MSC in spheroid form, which has been shown to alter the cellular phenotype. Alginate encapsulated cells are another form of mechanical confinement, and have additional benefits including resistance to immunological attack, making them a practical therapy for treatment of CLTI patients. 
 
 Project Methods: In this work, cells were encapsulated in 2% alginate using a centrifugation method. Media from these cells along with others were analyzed for IL-10 and IL-33 using ELISA. Mouse tissue samples were stained with WGA-555 antibody and analyzed using a scanning microscope. Effects on tissue perfusion were measured with Laser Doppler Perfusion Imaging. At the time of this abstract, the media from encapsulated and naked MSCs is being used to culture myoblasts, looking at cell growth. 
 
 Results: ELISA results did not show significant increases in IL-10 or IL-33 for encapsulated vs. non-encapsulated cells. LDPI has shown an increased perfusion rate for hindlimbs treated with encapsulated MSCs vs naked MSCs. Muscle fiber analysis is ongoing, but initial data appears promising. 
 
 Conclusion and Potential Impact: This experiment provides a starting point for improving and expanding cell therapy for critical limb ischemia, potentially resulting in better outcomes for diabetic patients and preventing lower limb amputations. The encapsulation process also has value in other types of cell therapy, as it could protect cells from host defenses and increase dwell time.

Breast tumor parameter estimation and interactive 3D thermal tomography using discrete thermal sensor data

This work uses a simple low-cost wearable device embedded with discrete thermal sensors to map the breast skin surface temperature. A methodology has been developed to estimate diameter, blood perfusion, metabolic heat generation and location in X, Y, Z coordinate of tumor from this discrete set of data. An interactive 3D thermal tomography was developed which provides a detailed 3D thermal view of the breast anatomy. Using this system, the user can interactively rotate and slice the 3D thermal image of the breast for a detailed study of the tumor. Finite element method (FEM) and an evolution-based inverse method were used for the parameter estimation. The method was first validated using phantom experiments and the results obtained were within an error of 10% (0.005 W cm−3) for heat generation and 15% (0.3 cm) for heater location. Further validation was carried out through clinical trials on 60 human subjects. Estimated blood perfusion rate and metabolic heat generation rate exhibit distinguishable difference between cancerous and non-cancerous breast. Estimated diameter and location of tumor in cancerous breast shows good agreement with the actual clinical reports. We have obtained a sensitivity of 82.78% and specificity of 87.09%. Proposed breast tumor parameter estimation methodology with interactive 3D thermal tomography is a good screening tool for breast cancer detection and also useful for clinicians to find out location including depth.

Analysis of the effect of external heating in the human tissue: A finite element approach

Abstract Thermal therapy which involves either raising or lowering tissue temperature to treat malignant cells needs precise acknowledgment of thermal history inside the biological system to ensure effective treatment. For this purpose, this study presents a two-dimensional unsteady finite element model (FEM) of the bioheat transfer problem based on Pennes bio-heat equation to analyze the thermal response of tissue subject to external heating. Crank-Nikolson scheme was used for the unsteady solution. A finite element code was developed using C language to calculate results. The obtained numerical result was compared with the analytical and other numerical results available in the literature. A good agreement was found from the comparison. Temperature distribution inside the human body due to constant and sinusoidal spatial and surface heating were analyzed. Response to point heating was also investigated. Moreover, a sensitivity analysis was carried out to know the effect of various parameters, i.e. blood temperature, thermal conductivity, and blood perfusion rate on tissue temperature. The outcome of this study will be helpful for the researchers and physicians involved in the thermal treatment of human tissue.

Detection of Hypoxic Regions in the Bone Microenvironment.

Oxygen serves as a critical environmental factor essential for maintaining the physiological state of a tissue. Hypoxia, or low oxygen, triggers a cascade of events which allows for cells to adapt to low oxygen tensions and to facilitate oxygen delivery required to maintain tissue homeostasis. In the bone microenvironment (BME), vascular heterogeneity, poor perfusion rates of blood vessels, and high metabolic activity of hematopoietic cells result in the generation of a unique hypoxic landscape. Importantly, in this region, hypoxia and its downstream effectors are associated with establishing stem cell niches and regulating the differentiation of committed progenitors. Given the functional importance of the hypoxic bone niche, visualizing regions of hypoxia may provide valuable insights into the mechanisms that regulate tissue homeostasis. Here, we describe the utilization of the nitroimidazole derivative, pimonidazole, to detect hypoxic regions within the BME.

Establishment and optimization of a high-throughput mimic perfusion model in ambr® 15.

To establish an automated high-throughput mimic perfusion scale-down model (SDM) in ambr® 15 system. An optimized SDM for mimic perfusion was developed in ambr® 15 system. Cell retention in ambr® 15 was realized by sedimentation and supernatant removal with a retention rate > 95%. Although the SDM couldn't reach the viable cell density (VCD) at a bench scale bioreactor (BR), it maintained VCD at approximately 30 × 106 cells/mL with a cell bleeding rate estimated theoretically and predicted the cell specific perfusion rate (CSPR). A base-feeding strategy was developed to alleviate the pH drop during sedimentation which would adversely have an impact on cell growth, and showed an apparent cell viability improvement from 79.6% (control) to 90.1% on Day 18. The optimized SDM for mimic perfusion was employed for media screening in two cell lines. A small-scale high-throughput perfusion model in ambr® 15 was developed, optimized to improve cell viability, and as a result, utilized for media screening in two cell lines.

The Chft+ Sensor: A Novel Method to Measure Perfusion Abnormalities in Sickle Cell Disease

Introduction: Peripheral perfusion limitation is a potential biomarker of the severity and progression of sickle cell disease (SCD). Currently, there exists no direct means of quantifying perfusion deficits in SCD patients. Transcranial doppler ultrasonography offers a surrogate measure of perfusion and is highly operator dependent. Routine clinical screening of perfusion abnormalities with alternative modalities (e.g., positron emission tomography and magnetic resonance imaging) is challenging given high cost, requirement for sedation in young children, and need for trained personnel. The Combined Heat-Flux Temperature Sensor (CHFT+) is a novel noninvasive bio-heat perfusion sensor that measures peripheral perfusion in real time at depths of up to 1 cm by applying a minimal amount of heat to the skin surface. Because perfusion limitation is a hallmark of SCD, an improved understanding of its pathophysiology could potentially empower both patients and their physicians. The aim of this study was to evaluate the ability of the CHFT+ to detect differences in peripheral perfusion between healthy volunteers and patients with SCD. Materials and Methods: The present study is an ongoing, non-randomized pilot study that aims to test the CHFT+ sensor's ability to detect impaired perfusion is pediatric SCD patients. We are actively enrolling pediatric patients (age 3-17) with SCD and healthy volunteers from 2 pediatric clinics to test the sensor. Peripheral perfusion measurements were obtained at 5 locations on the body (e.g., forehead, forearms, palms). All measurements were normalized against forehead perfusion values to account for individual variations. An independent-samples t-test was conducted to compare average rates of perfusion in patients with SCD and in healthy volunteers. The goal enrollment for this study is 52 patients (26 with SCD, 26 healthy controls) to detect a two-fold difference in perfusion with a power of 0.80. Interim Results and Discussion: To date, 31 participants have been enrolled, 10 (32%) of whom were patients with SCD. Overall, average perfusion rates were lower in the SCD group when compared to the healthy group, although these differences were not statistically significant. Representative measurements of perfusion in the right and left forearms, normalized against forehead rates, are shown in Figure 1. Normalized left forearm perfusion in healthy controls vs. SCD patients: avg = 1.77, SD = 0.95 vs. avg = 1.28, SD = 0.52, respectively [t(27) = 1.80, p = 0.08]; see Fig. 1a. Normalized right forearm perfusion in healthy controls vs. SCD patients: avg = 1.80, SD = 1.01 vs. avg = 1.31, SD = 0.60, respectively [t(25) = 1.55, p = 0.13]); see Fig. 1b. Conclusions:At this time, our data suggest that the novel CHFT+ sensor is capable of detecting a modest difference in peripheral perfusion in children with SCD versus healthy controls, but this difference is not statistically significant due to limited enrollment. Additional enrollment will further define the utility of the CHFT+ sensor in this clinical population. Future studies should evaluate the sensor's capability to detect perfusion deficits in the adult SCD population, as well as measure perfusion variations that occur during SCD vaso-occlusive crises. Disclosures Diller: FluxTeq:Other: Partner.

Increased serum peripheral C-reactive protein is associated with reduced brain barriers permeability of TSPO radioligands in healthy volunteers and depressed patients: implications for inflammation and depression

The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood–brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity.To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts (N = 51 patients and N = 25 controls) and a second study where peripheral inflammation in N = 7 healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100β, that was unchanged.These results suggest a different model of peripheral-to-central immunity interaction whereas peripheral inflammation may cause a reduction in BBB permeability. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms.

Control of IgG glycosylation in CHO cell perfusion cultures by GReBA mathematical model supported by a novel targeted feed, TAFE

The N-linked glycosylation pattern is an important quality attribute of therapeutic glycoproteins. It has been reported by our group and by others that different carbon sources, such as glucose, mannose and galactose, can differently impact the glycosylation profile of glycoproteins in mammalian cell culture. Acting on the sugar feeding is thus an attractive strategy to tune the glycan pattern. However, in case of feeding of more than one carbon source simultaneously, the cells give priority to the one with the highest uptake rate, which limits the usage of this tuning, e.g. the cells favor consuming glucose in comparison to galactose.We present here a new feeding strategy (named ‘TAFE’ for targeted feeding) for perfusion culture to adjust the concentrations of fed sugars influencing the glycosylation. The strategy consists in setting the sugar feeding such that the cells are forced to consume these substrates at a target cell specific consumption rate decided by the operator and taking into account the cell specific perfusion rate (CSPR). This strategy is applied in perfusion cultures of Chinese hamster ovary (CHO) cells, illustrated by ten different regimes of sugar feeding, including glucose, galactose and mannose. Applying the TAFE strategy, different glycan profiles were obtained using the different feeding regimes. Furthermore, we successfully forced the cells to consume higher proportions of non-glucose sugars, which have lower transport rates than glucose in presence of this latter, in a controlled way.In previous work, a mathematical model named Glycan Residues Balance Analysis (GReBA) was developed to model the glycosylation profile based on the fed carbon sources. The present data were applied to the GReBA to design a feeding regime targeting a given glycosylation profile. The ability of the model to achieve this objective was confirmed by a multi-round of leave-one-out cross-validation (LOOCV), leading to the conclusion that the GReBA model can be used to design the feeding regime of a perfusion cell culture to obtain a desired glycosylation profile.

Computational Modeling of Cardiac Ablation Incorporating Electrothermomechanical Interactions

AbstractThe application of radio frequency ablation (RFA) has been widely explored in treating various types of cardiac arrhythmias. Computational modeling provides a safe and viable alternative to ex vivo and in vivo experimental studies for quantifying the effects of different variables efficiently and reliably, apart from providing a priori estimates of the ablation volume attained during cardiac ablation procedures. In this contribution, we report a fully coupled electrothermomechanical model for a more accurate prediction of the treatment outcomes during the radio frequency cardiac ablation. A numerical model comprising of cardiac tissue and the cardiac chamber has been developed in which an electrode has been inserted perpendicular to the cardiac tissue to simulate actual clinical procedures. Temperature-dependent heat capacity, electrical and thermal conductivities, and blood perfusion rate have been considered to model more realistic scenarios. The effects of blood flow and contact force of the electrode tip on the treatment outcomes of a fully coupled model of RFA have been systematically investigated. The numerical study demonstrates that the predicted ablation volume of RFA is significantly dependent on the blood flow rate in the cardiac chamber and also on the tissue deformation induced due to electrode insertion depth of 1.5 mm or higher.

Derepression of glomerular filtration, renal blood flow and antioxidant defence in patients with type 2 diabetes at high-risk of cardiorenal disease

BackgroundThe role of antioxidant status on microvascular blood flow and glomerular filtration (eGFR) in patients with type 2 diabetes and hypertension whose risk of progressive renal disease varies by ethnicity is unknown. MethodsAdult, non-Caucasian (n = 101) and Caucasian (n = 69) patients with type 2 diabetes, hypertension and/or microalbuminuria and an eGFR > 45 mL/min/1.73 m2 were randomised to receive 400 IU vitamin E and/or 20 μg selenium daily or matching placebo. eGFR (CKD-EPI) was measured at baseline, 3,6 and 12 months and renal blood flow by contrast-enhanced ultrasonography in a sub-group (n = 9) at baseline and 3 months by assessing the area under the time intensity curve (TIC). Circulating glutathione peroxidase 3 (GPx-3) activity was measured as a biomarker of oxidative defence status. ResultsThe time to change in eGFR was shortest with combined vitamin E and selenium than usual care (5.6 [4.0–7.0] vs 8.9 [6.8–10.9 months]; p = 0.006). Area under the TIC was reduced compared to baseline (38.52 [22.41–90.49] vs 123 [86.98–367.03]dB.s; P ≤ 0.05 and 347 [175.88–654.92] vs 928.03 [448.45–1683]dB.s; P ≤ 0.05, respectively] at 3 months suggesting an increase in rate of perfusion. The proportional change in eGFR at 12 months was greater in the group whose GPx-3 activity was above, compared with those below the cohort median (360 U/L) in the non-Caucasian and the Caucasian groups (19.1(12.5–25.7] % vs 6.5[-3.5 to 16.5] % and 12.8 [0.7 to 24] % vs 0.2 [-6.1 to 6.5] %). ConclusionIn these patients with type 2 diabetes and early CKD, antioxidant treatment derepresses renal blood flow and a rise in eGFR correlated directly with GPx-3 activity. SignificanceDiabetes mellitus is the world's leading cause of end-stage renal disease which has a predilection for black and minor ethnic groups compared with Caucasians. The differences in risk despite the benefits of conventional care may be related to oxidative stress. We found that glomerular filtration and renal blood flow is suppressed when renal function is preserved in high-risk patients with type 2 diabetes. Conventional care supplemented with selenium - the co-factor for glutathione peroxidase-3 (GPx-3) - improves renal perfusion and increase glomerular filtration according to host antioxidant defence determined by GPx-3 activity. Circulating GPx-3 activity warrants further investigation as a novel biomarker of reversible haemodynamic changes in early diabetic kidney disease to better enable targeting of renoprotective strategies.

Bio-heat response of skin tissue based on three-phase-lag model

In this article, the thermal response of skin tissue is investigated based on three-phase-lag (TPL) model of heat conduction. The governing equation of bio-heat conduction is established by introducing both the TPL model of heat conduction and a modified energy conservation equation. The analytical solution is obtained by adopting the method of separation of variables and a parametric study on temperature responses in TPL model is carried out. It is shown that the TPL model can predict both the diffusion and wave characteristics of bio-heat conduction. Increasing the phase-lag of thermal displacement gradient would result in the rise of thermal propagation speed and decrease the temperature in affected zone. The perfusion rate of arterial blood has no obvious effect on thermal propagation velocity and thermal propagation lagging. Increasing of the rate of blood perfusion contributes to decreasing the temperature of steady state.

Specific parameters of operation of the minimized system for cardioplegia in children. Bench test

It is very important to observe all the parameters of cardioplegia when protecting myocardium during cardiac surgery. To perform this task, it is necessary to have clear understanding of properties of the elements of the extracorporeal circuit of cardiopulmonary bypass. The objective : to develop a test model and using it to evaluate technical capabilities of blood cardioplegic system reducing the filling volume of the heat exchange chamber and the system supplying solution to the myocardium. Subjects and methods . A model of a neonatal cardiopulmonary bypass circuit was tested, it included an oxygenator and the cardioplegic system with a 7-ml heat exchange chamber; changes in the pressure and temperature in key nodes of the extracorporeal and cardioplegic circuits were assessed when the pump velocity, ambient temperature and fluid temperature in the main circuit were changed. Results . This modification provides a wide range of liquid volumetric velocities. Maintaining the selected variant of blood cardioplegia and safe pressure within the cardioplegic circuit is ensured at the perfusion rate of up to 350 ml/min. With normothermal circulation and air temperature in the operating room of 23°C, parameters of the cardioplegic circuit and solution delivery system allows maintaining the solution temperature within the range from 16 to 19°C. When the solution is cooled in a heat exchanger down to 4°C, the temperature of the final cardioplegic solution is maintained within 12-17°C; and with normothermal perfusion, air temperature in the operating room of 15°C and the solution temperature in the heat exchange chamber of 4°C, the temperature of the final cardioplegic solution can be within 6‒13°C. With perfusion in the mode of moderate hypothermia (32°C), air temperature in the operating room 15°C and temperature in the heat exchange chamber 4°C, the final cardioplegic solution can be delivered at the temperature from 5 to 9°C. Conclusions . The proposed test model allows investigating aimed to find out additional characteristics of the cardioplegic circuit. Ambient air temperature, cardioplegic pump velocity and main circuit fluid temperature are the main factors influencing the final cardioplegic solution temperature. When using the studied variant of the cardioplegic circuit assembly, the maintenance of the selected variant of blood cardioplegia and safe pressure inside the cardioplegic circuit are ensured at a perfusion rate of up to 350 ml/min.

Me2SO perfusion time for whole-organ cryopreservation can be shortened: Results of micro-computed tomography monitoring during Me2SO perfusion of rat hearts.

Cryopreservation of whole organs and specific tissues is an important and continually expanding field of medicine. The protocols currently used for organ preservation do not ensure survivability and functionality; the protocols for ovarian tissue lead to acceptable outcomes, but these are still capable of further improvement. In general, cryopreservation protocols need to be optimized. One important approach to improving cryopreservation protocols in general involves reducing exposure to cytotoxic cryoprotective agents prior to freezing. This study, therefore, evaluated the real-time tissue penetration of dimethyl sulfoxide, a cryoprotective agent that is widely used in cryopreservation. Dimethyl sulfoxide penetration in rat hearts perfused with a 15% (v/v) dimethyl sulfoxide solution was examined in real-time using dynamic contrast-enhanced micro-computed tomography imaging. Viability of cardiomyocytes was not significantly affected by the dimethyl sulfoxide perfusion procedure. Two different perfusion rates were evaluated and compared with perfusion using a common iodine-based contrast agent (iomeprol). The dynamic contrast-enhanced micro-computed tomography imaging data showed that dimethyl sulfoxide flushes both the extracellular and intracellular spaces in rat heart tissue to 95% equilibration after ≈ 35 s via perfusion. Subsequent wash-out via perfusion is completed to 95% within ≈ 49 s. The equilibration duration routinely used in dimethyl sulfoxide–based protocols for cryopreservation should therefore be questioned. Shorter incubation duration would perhaps be sufficient, as well as being beneficial in relation to cell survivability. It would be helpful to have techniques for non-invasive real-time monitoring of the penetration of cryoprotective agents and such techniques should be used to revise cryopreservation protocols. Switching to perfusion-based equilibration procedures might be beneficial, if feasible.

Analysis of nonlinear bioheat transfer equation in magnetic fluid hyperthermia

The objective of this study is to examine the role of blood perfusion in magnetic fluid hyperthermia by drug delivery. Although increasing blood perfusion due to high local temperature difference refers to the intelligent response of the human body, some researchers are accustomed to employing a constant rate of blood perfusion in the bioheat transfer equation. In this study, we considered a variable volumetric rate for blood perfusion in tissue, experimentally and numerically by Galerkin method. To validate the results obtained from numerical methods, an experimental procedure proposed. Furthermore, in order to transfer magnetic fluid by drug delivery, infusion pomp by which the saline serum with nanoparticles through the vein and artery was employed to make a spherical distribution in tissue. This circulation made it possible to transfer nanoparticles to tissue without any injection. After 60 minutes and changing the dark color of the saline serum to light clear, high amount of nanoparticles (about 90 %) was transferred to the tissue. After slicing the tissue, the rather spherical distribution of nanoparticles may be illustrated. Afterward, that circulation at the rate equal to blood perfusion has been made to simulate blood perfusion in dead tissue. To measure temperature, seven Lm35 sensors have been inserted into the tissue to report temperature differences. Based on results, there was seen a significant change in hyperthermic temperature difference in comparison with results obtained from Pennes’ bioheat transfer equation. Additionally, a difference of about 5–10 % was seen between numerical and experimental results.

Bone grafting history affects soft tissue healing following implant placement.

This study aimed to determine and compare soft tissue healing outcomes following implant placement in grafted (GG) and non-grafted bone (NGG). Patients receiving single implant in a tooth-bound maxillary non-molar site were recruited. Clinical healing was documented. Volume and content of wound fluid (WF; at 3, 6, and 9 days) were compared with adjacent gingival crevicular fluid (GCF; at baseline, 1, and 4 months). Buccal flap blood perfusion recovery and changes in bone thickness were recorded. Linear mixed model regression analysis and generalized estimating equations with Bonferroni adjustments were conducted for repeated measures. Twenty-five patients (49 ± 4 years; 13 males; nine NGG) completed the study. Soft tissue closure was slower in GG (P<0.01). Differential response in WF/GCF protein concentrations was detected for ACTH (increased in GG only) and insulin, leptin, osteocalcin (decreased in NGG only) at day 6 (P ≤0.04), with no inter-group differences at any time(P>0.05). Blood perfusion rate decreased immediately postoperatively (P<0.01, GG) followed by 3-day hyperemia (P>0.05 both groups). The recovery to baseline values was almost complete for NGG whereas GG stayed ischemic even at 4 months (P=0.05). Buccal bone thickness changes were significant in GG sites (P ≤ 0.05). History of bone grafting alters the clinical, physiological, and molecular healing response of overlying soft tissues after implant placement surgery.