A Custom-Tailored Multichannel Pressure Monitoring System Designed for Experimental Surgical Model of Abdominal Compartment Syndrome.

In experimental medicine, a wide variety of sensory measurements are used. One of these is real-time precision pressure measurement. For comparative studies of the complex pathophysiology and surgical management of abdominal compartment syndrome, a multichannel pressure measurement system is essential. An important aspect is that this multichannel pressure measurement system should be able to monitor the pressure conditions in different tissue layers, and compartments, under different settings. We created a 12-channel positive-negative sensor system for simultaneous detection of pressure conditions in the abdominal cavity, the intestines, and the circulatory system. The same pressure sensor was used with different measurement ranges. In this paper, we describe the device and major experiences, advantages, and disadvantages. The sensory systems are capable of real-time, variable frequency sampling and data collection. It is also important to note that the pressure measurement system should be able to measure pressure with high sensitivity, independently of the filling medium (gas, liquid). The multichannel pressure measurement system we developed was well suited for abdominal compartment syndrome experiments and provided data for optimizing the method of negative pressure wound management. The system is also suitable for direct blood pressure measurement, making it appropriate for use in additional experimental surgical models.

ß-Tricalcium Phosphate-Modified Aerogel Containing PVA/Chitosan Hybrid Nanospun Scaffolds for Bone Regeneration.

Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of ß-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using 18F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice.

In Vivo Preclinical Assessment of ß-Amyloid-Affine [11C]C-PIB Accumulation in Aluminium-Induced Alzheimer's Disease-Resembling Hypercholesterinaemic Rat Model.

Aluminum (Al) excess and hypercholesterinaemia are established risks of Alzheimer's disease (AD). The aim of this study was to establish an AD-resembling hypercholesterinaemic animal model-with the involvement of 8 week and 48 week-old Fischer-344 rats-by Al administration for the safe and rapid verification of ß-amyloid-targeted positron emission tomography (PET) radiopharmaceuticals. Measurement of lipid parameters and ß-amyloid-affine [11C]C-Pittsburgh Compound B ([11C]C-PIB) PET examinations were performed. Compared with the control, the significantly elevated cholesterol and LDL levels of the rats receiving the cholesterol-rich diet support the development of hypercholesterinaemia (p ≤ 0.01). In the older cohort, a notably increased age-related radiopharmaceutical accumulation was registered compared to in the young (p ≤ 0.05; p ≤ 0.01). A monotherapy-induced slight elevation of mean standardised uptake values (SUVmean) was statistically not significant; however, adult rats administered a combined diet expressed remarkable SUVmean increment compared to the adult control (SUVmean: from 0.78 ± 0.16 to 1.99 ± 0.28). One and two months after restoration to normal diet, the cerebral [11C]C-PIB accumulation of AD-mimicking animals decreased by half and a third, respectively, to the baseline value. The proposed in vivo Al-induced AD-resembling animal system seems to be adequate for the understanding of AD neuropathology and future drug testing and radiopharmaceutical development.

In Vivo Assessments of Mesoblastic Nephroma (Ne/De) and Myelomonoblastic Leukaemia (My1/De) Tumour Development in Hypercholesterolemia Rat Models.

Given the rising prevalence of lipid metabolic disorders and malignant diseases, we aimed to establish an in vivo hypercholesterinaemic tumour-bearing rat model for the induction and assessment of these conditions. A normal standard CRLT/N, 2 (baseline),- or 4 (2 + 2, pretreated)-week-long butter and cholesterol rich (BCR) diet was applied to mesoblastic nephroma (Ne/De) and myelomonoblastic leukaemia (My1/De) tumour-bearing and healthy control Long­Evans and Fischer 344 rats. The beginning of chow administration started in parallel with tumour induction and the 2 weeks of pre-transplantation in the baseline and pretreated groups, respectively. Fourteen days post-inoculation, the measurement of lipid parameters and [18F]F-FDG PET/MRI examinations was executed. The comparable lipid status of baseline healthy and tumorous rats proves that regardless of tumour presence, BCR-based hypercholesterolemia was achieved. A higher tumour mass among pretreated tumorous animals was found when compared to the control groups (p < 0.05, p < 0.01). Further, a visually greater [18F]F-FDG accumulation was observed in pretreated BCR tumorous animals; however, the quantitative data (SUVmean: 9.86 ± 0.98, 9.68 ± 1.24; SUVmax: 19.63 ± 1.20; 17.56 ± 3.21 for Ne/De and My1/De, respectively) were not statistically significantly different from those of the CRLT/N tumorous rats (SUVmean: 8.40 ± 1.42, 7.22 ± 1.06 and SUVmax: 15.99 ± 2.22, 12.46 ± 1.96 for control Ne/De and My1/De, respectively). Our model seems to be appropriate for simultaneously investigating hypercholesterolemia and cancer in the same rat.

Pefloxacin induced changes in serotonergic innervation and mast cell number in rat salivary glands.

Pefloxacin is a second-generation fluoroquinolone antibiotic. Besides its advantageous characteristics, side effects including the hypofunction of salivary glands, decreased saliva production, and peripheral neuropathy were observed during the administration of pefloxacin. The aim of this study was to investigate the changes in the number of serotonergic immunoreactive fibers and mast cells after pefloxacin treatment in the parotid and sublingual glands of rats to detect the possible neurotoxic effect of pefloxacin. The adult female rats were treated with intraperitoneal (i.p.) injection of pefloxacin for three or seven days (at a concentration of 20 mg/100g body weight) and the serotonergic innervation pattern along with the change in mast cell number were evaluated by using histochemistry and immunohistochemistry in the parotid and sublingual glands. We found that a three-day treatment significantly increased the number of immunoreactive serotonergic nerve fibers, but after a seven-day treatment the number of serotonin positive nerve fibers decreased almost to values of the control group. The alteration of mast cell number was parallel with the changes of the serotonin positive fibers during the treatment. These results suggest that pefloxacin treatment can modify the finely controlled communication between the immune- and the peripheral nervous systems, resulting neurogenic inflammatory process. The background of this process is the altered serotonergic innervation and the increased number of activated mast cells releasing different mediators for example histamine, which can finally lead to reduced number of serotonin positive nerve fibers after a seven-day treatment of pefloxacin leading to atrophy and hypofunction of the salivary glands.

Carotid-Jugular Fistula Model to Study Systemic Effects and Fistula-Related Microcirculatory Changes.

BACKGROUND: Arteriovenous fistulae impair the distal circulation, but their effects at the microcirculatory level are not well understood. This study presents the carotid-jugular fistula (CJF) as a model to evaluate fistula-related microcirculatory and systemic changes. MATERIALS AND METHODS: Female Wistar rats were anesthetized and divided into a fistula group (FG, n = 10) and a sham group (SG, n = 6). End-to-end anastomosis was performed between the right carotid artery and the jugular vein in the FG. The hemodynamic status was followed for 6 weeks. On the sixth postoperative week, liver and kidney microcirculation was measured using laser Doppler; then microcirculatory changes were assessed after occlusion of the carotid artery. At the end of the experiment, histological samples were taken and the weights of the organs were measured. RESULTS: The heart rate and systolic blood pressure decreased significantly due to the CJF. Laser Doppler showed a reduction in liver blood flow units (BFU) in the FG in comparison with the SG (p = 0.01), and they increased (p < 0.01) after occlusion of the fistula. Kidney BFU showed slight changes only. The comparative morphological study revealed significant increases in heart weight (p < 0.001) and left ventricular hypertrophy (p = 0.008) in the FG. CONCLUSION: Beside hemodynamic and morphologic changes, a CJF causes a deterioration in the microcirculation of the liver rather than of the kidney, but occlusion of the CJF immediately reverses these changes.

A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity.

Adenosine, a key extracellular signaling mediator, regulates several aspects of metabolism by activating 4 G-protein-coupled receptors, the A1, A2A, A2B, and A3 adenosine receptors (ARs). The role of A2AARs in regulating high-fat-diet (HFD)-induced metabolic derangements is unknown. To evaluate the role of A2AARs in regulating glucose and insulin homeostasis in obesity, we fed A2AAR-knockout (KO) and control mice an HFD for 16 wk to initiate HFD-induced metabolic disorder. We found that genetic deletion of A2AARs caused impaired glucose tolerance in mice fed an HFD. This impaired glucose tolerance was caused by a decrease in insulin secretion but not in insulin sensitivity. Islet size and insulin content in pancreata of A2AAR-deficient mice were decreased compared with control mice after consuming an HFD. A2AAR-KO mice had decreased expression of the ß-cell-specific markers pdx1, glut2, mafA, and nkx6.1 and increased expression of the dedifferentiation markers sox2 and hes1. Ex vivo islet experiments confirmed the role of A2AARs in protecting against decreased insulin content and release caused by HFD. Other experiments with bone marrow chimeras revealed that inflammation was not the primary cause of decreased insulin secretion in A2AAR-KO mice. Altogether, our data showed that A2AARs control pancreatic dysfunction in HFD-induced obesity.-Csóka, B., Töro, G., Vindeirinho, J., Varga, Z. V., Koscsó, B., Németh, Z. H., Kókai, E., Antonioli, L., Suleiman, M., Marchetti, P., Cseri, K., Deák, Á., Virág, L., Pacher, P., Bai, P., Haskó, G. A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity.

Pressure Distribution during Negative Pressure Wound Therapy of Experimental Abdominal Compartment Syndrome in a Porcine Model.

(1) Introduction: Negative pressure wound therapy (NPWT) is a frequently applied open abdomen (OA) treatment. There are only a few experimental data supporting this method and describing the optimal settings and pressure distribution in the abdominal cavity during this procedure. The aim of our study was to evaluate pressure values at different points in the abdominal cavity during NPWT in experimental abdominal compartment syndrome (ACS) animal model; (2) Methods: In this study (permission Nr. 13/2014/UDCAW), 27 Hungahib pigs (15.4-20.2 kg) were operated on. ACS was generated by implanting a plastic bag in the abdomen through mini-laparotomy and filled with 2100-3300 mL saline solution (37 °C) to an intraabdominal pressure (IAP) of 30 mmHg. After 3 h, NPWT (Vivano Med® Abdominal Kit, Paul Hartmann AG, Germany) or a Bogota bag was applied. The NPWT group was divided into -50, -100 and -150 mmHg suction groups. Pressure distribution to the abdominal cavity was monitored at 6 different points of the abdomen via a multichannel pressure monitoring system; (3) Results: The absolute pressure levels were significantly higher above than below the protective layer. The values of the pressure were similar in the midline and laterally. Amongst the bowels, the pressure values changed periodically between 0 and -12 mmHg which might be caused by peristaltic movements; (4) Conclusions: The porcine model of the present study seems to be well applicable for investigating ACS and NPWT. It was possible to provide valuable information for clinicians. The pressure was well distributed by the protective layer to the lateral parts of the abdomen and this phenomenon did not change considerably during the therapy.

Assessment of cerebral circulation in a porcine model of intravenously given E. coli induced fulminant sepsis.

BACKGROUND: The aim of the present work was to assess cerebral hemodynamic changes in a porcine model of E.coli induced fulminant sepsis. METHODS: Nineteen healthy female Hungahib pigs, 10-12 weeks old, randomly assigned into two groups: Control (n = 9) or Septic Group (n = 10). In the Sepsis group Escherichia coli culture suspended in physiological saline was intravenously administrated in a continuously increasing manner according to the following protocol: 2 ml of bacterial culture suspended in physiological saline was injected in the first 30 min, then 4 ml of bacterial culture was administered within 30 min, followed by infusion of 32 ml bacterial culture for 2 h. Control animals received identical amount of saline infusion. Systemic hemodynamic parameters were assessed by PiCCo monitoring, and cerebral hemodynamics by transcranial Doppler sonography (transorbital approach) in both groups. RESULTS: In control animals, systemic hemodynamic variables and cerebral blood flow velocities and pulsatility indices were relatively stable during the entire procedure. In septic animals shock developed in 165 (IQR: 60-255) minutes after starting the injection of E.coli solution. Blood pressure values gradully decreased, whereas pulse rate increased. A decrease in cardiac index, an increased systemic vascular resistance, and an increased stroke volume variation were observed. Mean cerebral blood flow velocity in the middle cerebral artery did not change during the procedure, but pulsatility index significantly increased. CONCLUSIONS: There is vasoconstriction at the level of the cerebral arterioles in the early phase of experimental sepsis that overwhelmes autoregulatory response. These results may serve as additional pathophysiological information on the cerebral hemodynamic changes occurring during the septic process and may contribute to a better understanding of the pathomechanism of septic encephalopathy.

Effect of Bile on Hemodynamics and Blood Micro-Rheological Parameters in Experimental Models of Bilhemia.

As a rare complication of liver injury and certain interventions, bile can enter the bloodstream depending on the pressure gradient, resulting in bilhemia. Its micro-rheological and hemodynamic effects are still unclear. We aimed to study these parameters in experimental bilhemia models. Under general anesthesia, via laparotomy, bile was obtained by gallbladder puncture from pigs and by choledochal duct cannulation from rats. In vitro, 1 µL and 5 µL of bile were mixed with 500 µL of anticoagulated autologous blood. The systemic effect was also assessed (i.v. bile, 200 µL/bwkg). Hemodynamic and hematological parameters were monitored, and red blood cell (RBC) deformability and aggregation were determined. RBC deformability significantly decreased with the increasing bile concentration in vitro (1 µL: p = 0.033; 5 µL: p < 0.001) in both species. The RBC aggregation index values were concomitantly worsened (1 µL: p < 0.001; 5 µL: p < 0.001). The mean arterial pressure and heart rate decreased by 15.2 ± 6.9% and 4.6 ± 2.1% in rats (in 10.6 ± 2.6 s) and by 32.1 ± 14% and 25.2 ± 11.63% in pigs (in 48.3 ± 18.9 s). Restoration of the values was observed in 45 ± 9.5 s (rats) and 130 ± 20 s (pigs). Bilhemia directly affected the hemodynamic parameters and caused micro-rheological deterioration. The magnitude and dynamics of the changes were different for the two species.

Hemorheological and Microcirculatory Relations of Acute Pancreatitis.

Acute pancreatitis still means a serious challenge in clinical practice. Its pathomechanism is complex and has yet to be fully elucidated. Rheological properties of blood play an important role in tissue perfusion and show non-specific changes in acute pancreatitis. An increase in blood and plasma viscosity, impairment of red blood cell deformability, and enhanced red blood cell aggregation caused by metabolic, inflammatory, free radical-related changes and mechanical stress contribute to the deterioration of the blood flow in the large vessels and also in the microcirculation. Revealing the significance of these changes in acute pancreatitis may better explain the pathogenesis and optimize the therapy. In this review, we give an overview of the role of impaired microcirculation by changes in hemorheological properties in acute pancreatitis.

Interspecies Diversity of Osmotic Gradient Deformability of Red Blood Cells in Human and Seven Vertebrate Animal Species.

Plasma and blood osmolality values show interspecies differences and are strictly regulated. The effect of these factors also has an influence on microrheological parameters, such as red blood cell (RBC) deformability and aggregation. However, little is known about the interspecies differences in RBC deformability at various blood osmolality levels (osmotic gradient RBC deformability). Our aim was to conduct a descriptive-comparative study on RBC osmotic gradient deformability in several vertebrate species and human blood. Blood samples were taken from healthy volunteers, dogs, cats, pigs, sheep, rabbits, rats, and mice, to measure hematological parameters, as well as conventional and osmotic gradient RBC deformability. Analyzing the elongation index (EI)-osmolality curves, we found the highest maximal EI values (EI max) in human, dog, and rabbit samples. The lowest EI max values were seen in sheep and cat samples, in addition to a characteristic leftward shift of the elongation index-osmolality curves. We found significant differences in the hyperosmolar region. A correlation of mean corpuscular volume and mean corpuscular hemoglobin concentration with osmoscan parameters was found. Osmotic gradient deformability provides further information for better exploration of microrheological diversity between species and may help to better understand the alterations caused by osmolality changes in various disorders.

Estradiol Valerate Affects Hematological and Hemorheological Parameters in Rats.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinological diseases in women. Although the risk of cardiovascular diseases is high in PCOS, the number of scientific publications describing hemorheological changes is not significant. We aimed to perform a comprehensive hematological and micro-rheological study on experimentally induced PCOS in rats.Wistar rats were divided into control (n = 9) and PCOS groups (n = 9), in which animals received single-dose estradiol valerate. Measurements were carried out before treatment and monthly for four months. Bodyweight, blood glucose concentration, hematological parameters, red blood cell (RBC) deformability, and aggregation were measured. A histological examination of the ovary was performed at the end of the experiment. The blood glucose level and the bodyweight were significantly elevated vs. base in the PCOS group. A significant decrease was seen in RBC count, hemoglobin, and hematocrit. The maximal elongation index showed a significant increase. PCOS also resulted in a significant increase in RBC aggregation index parameters. The histological and hormone examinations confirmed developed PCOS. The administration of estradiol valerate caused significant changes during the examined period in hematological and hemorheological parameters. Our results draw attention to the possible usefulness of micro-rheological investigations in further studies on PCOS.

In Vitro and In Vivo Studies of a Verapamil-Containing Gastroretentive Solid Foam Capsule.

Gastroretentive systems may overcome problems associated with incomplete drug absorption by localized release of the API in the stomach. Low-density drug delivery systems can float in the gastric content and improve the bioavailability of small molecules. The current publication presents verapamil-HCl-containing solid foam prepared by continuous manufacturing. Production runs were validated, and the foam structure was characterized by micro-CT scans and SEM. Dissolution properties, texture changes during dissolution, and floating forces were analyzed. An optimized formulation was chosen and given orally to Beagle dogs to determine the pharmacokinetic parameters of the solid foam capsules. As a result, a 12.5 m/m% stearic acid content was found to be the most effective to reduce the apparent density of capsules. Drug release can be described by the first-order model, where 70% of verapamil dissolved after 10 h from the optimized formulation. The texture analysis proved that the structures of the solid foams are resistant. Additionally, the floating forces of the samples remained constant during their dissolution in acidic media. An in vivo study confirmed the prolonged release of the API, and gastroscopic images verified the retention of the capsule in the stomach.

Changes of Hematological and Hemorheological Parameters in Rabbits with Hypercholesterolemia.

Hypercholesterolemia plays an important role in the development of atherosclerosis, leading to endothelial dysfunction, ischemic events, and increased mortality. Numerous studies suggest the pivotal role of rheological factors in the pathology of atherosclerosis. To get a more detailed hematological and hemorheological profile in hypercholesterolemia, we carried out an experiment on rabbits. Animals were divided into two groups: the control group (Control) was kept on normal rabbit chow, the high-cholesterol diet group (HC) was fed with special increased cholesterol-containing food. Hematological parameters (Sysmex K-4500 automate), whole blood and plasma viscosity (Hevimet-40 capillary viscometer), red blood cell (RBC) aggregation (Myrenne MA-1 aggregometer), deformability and mechanical stability (LoRRca MaxSis Osmoscan ektacytometer) were tested. The white blood cell and platelet count, mean corpuscular volume, and mean corpuscular hemoglobin were significantly higher in the HC group, while the RBC count, hemoglobin, and hematocrit values were lower than the Control data. Viscosity values corrected to 40% hematocrit were higher in the HC group. The RBC aggregation significantly increased in the HC vs. the Control. The HC group showed significantly worse results both in RBCs' deformability and membrane stability. In conclusion, the atherogenic diet worsens the hematological and macro- and micro-rheological parameters, affecting blood flow properties and microcirculation.

Examination of the relation between red blood cell aggregation and hematocrit in human and various experimental animals.

BACKGROUND: Red blood cell (RBC) aggregation plays an important role in the physiological processes of the microcirculation. The complete mechanism of aggregation is still unclear, and it is influenced by several cellular and plasmatic factors. One of these factors is the hematocrit (Hct). OBJECTIVE: We hypothesized that the relation of RBC aggregation and Hct differs between species. METHODS: From anticoagulated blood samples of healthy volunteers, rats, dogs, and pigs, 20, 40, and 60 %Hct RBC, autologous plasma suspensions were prepared. Hematological parameters and RBC aggregation was determined by light-transmission and light-reflection method. RESULTS: Suspensions at 20%and 60%Hct expressed lower RBC aggregation than of 40%Hct suspensions, showing inter-species differences. By curve fitting the Hct at the highest aggregation value differed in species (human: 45.25%- M 5 s, 40.86%- amp; rat: 44.44 %- M1 10 s, 39.37%- amp; dog: 42.48%- M 5 s, 44.29%- amp; pig: 47.63%- M 5 s, 52.8%- amp). CONCLUSION: RBC aggregation - hematocrit relation shows inter-species differences. Human blood was found to be the most sensitive for hematocrit changes. The more obvious differences could be detected by M 5 s by light-transmission method and amplitude parameter using light-reflection method.

In vitro effects of temperature on red blood cell deformability and membrane stability in human and various vertebrate species.

BACKGROUND: The effects of temperature on micro-rheological variables have not been completely revealed yet. OBJECTIVE: To investigate micro-rheological effects of heat treatment in human, rat, dog, and porcine blood samples. METHODS: Red blood cell (RBC) - buffer suspensions were prepared and immersed in a 37, 40, and 43°C heat-controlled water bath for 10 minutes. Deformability, as well as mechanical stability of RBCs were measured in ektacytometer. These tests were also examined in whole blood samples at various temperatures, gradually between 37 and 45°C in the ektacytometer. RESULTS: RBC deformability significantly worsened in the samples treated at 40 and 43°C, more expressed in human, porcine, rat, and in smaller degree in canine samples. The way of heating (incubation vs. ektacytometer temperation) and the composition of the sample (RBC-PBS suspension or whole blood) resulted in the different magnitude of RBC deformability deterioration. Heating affected RBC membrane (mechanical) stability, showing controversial alterations. CONCLUSION: Significant changes occur in RBC deformability by increasing temperature, showing inter-species differences. The magnitude of alterations is depending on the way of heating and the composition of the sample. The results may contribute to better understanding the micro-rheological deterioration in hyperthermia or fever.

Hematological, Micro-Rheological, and Metabolic Changes Modulated by Local Ischemic Pre- and Post-Conditioning in Rat Limb Ischemia-Reperfusion.

In trauma and orthopedic surgery, limb ischemia-reperfusion (I/R) remains a great challenge. The effect of preventive protocols, including surgical conditioning approaches, is still controversial. We aimed to examine the effects of local ischemic pre-conditioning (PreC) and post-conditioning (PostC) on limb I/R. Anesthetized rats were randomized into sham-operated (control), I/R (120-min limb ischemia with tourniquet), PreC, or PostC groups (3 × 10-min tourniquet ischemia, 10-min reperfusion intervals). Blood samples were taken before and just after the ischemia, and on the first postoperative week for testing hematological, micro-rheological (erythrocyte deformability and aggregation), and metabolic parameters. Histological samples were also taken. Erythrocyte count, hemoglobin, and hematocrit values decreased, while after a temporary decrease, platelet count increased in I/R groups. Erythrocyte deformability impairment and aggregation enhancement were seen after ischemia, more obviously in the PreC group, and less in PostC. Blood pH decreased in all I/R groups. The elevation of creatinine and lactate concentration was the largest in PostC group. Histology did not reveal important differences. In conclusion, limb I/R caused micro-rheological impairment with hematological and metabolic changes. Ischemic pre- and post-conditioning had additive changes in various manners. Post-conditioning showed better micro-rheological effects. However, by these parameters it cannot be decided which protocol is better.

Which remote ischemic preconditioning protocol is favorable in renal ischemia-reperfusion injury in the rat?

BACKGROUND: The optimal timing of remote ischemic preconditioning (RIPC) in renal ischemia-reperfusion (I/R) injury is still unclear. We aimed to compare early- and delayed-effect RIPC with hematological, microcirculatory and histomorphological parameters. METHODS: In anesthetized male CrI:WI Control rats (n = 7) laparotomy and femoral artery cannulation were performed. In I/R group (n = 7) additionally a 45-minute unilateral renal ischemia with 120-minute reperfusion was induced. The right hind-limb was strangulated for 3×10 minutes (10-minute intermittent reperfusion) 1 hour (RIPC-1 group, n = 7) or 24 hour (RIPC-24 group, n = 6) prior to the I/R. Hemodynamic, hematological parameters and organs' surface microcirculation were measured. RESULTS: Control and I/R group had the highest heart rate (p < 0.05 vs base), while the lowest mean arterial pressure (p < 0.05 vs RIPC-1) were found in the RIPC-24 group. The highest microcirculation values were measured in the I/R group (liver: p < 0.05 vs Control). The leukocyte count increased in I/R group (base: p < 0.05 vs Control), also this group's histological score was the highest (p < 0.05 vs Control). The RIPC-24 group had a significantly lower score than the RIPC-1 (p = 0.0025 vs RIPC-1). CONCLUSION: Renal I/R caused significant functional and morphological, also in the RIPC groups. According to the histological examination the delayed-effect RIPC method was more effective.

Microrheology, microcirculation and structural compensatory mechanisms of a chronic kidney disease rat model. A preliminary study.

BACKGROUND: Chronic kidney disease (CKD) models are known to study pathophysiology and various treatment methods. Renal dysfunction could influence erythrocytes through several pathways. However, hemorheological and microcirculatory relation of CKD models are not completely studied yet. OBJECTIVE: To evaluate erythrocyte micro-rheology, microcirculatory and structural compensatory mechanisms in a rat model of CKD. METHODS: Female Sprague-Dawley rats were subjected to nephrectomy group (NG, n = 6) or sham-operated group (SG, n = 6). NG rats were subjected to 5/6 nephrectomy in two stages. In SG no intervention was made on kidneys. Hemorheological and hematological measurements were carried out after each stage, and 5 weeks after the last operation. Histological and microcirculatory studies were done on the remaining kidney and compared with sham rats. RESULTS: Serum creatinine increased in NG (p = 0.008), accompanied with decrease of red blood cell count (p = 0.028) and hemoglobin (p = 0.015). Erythrocyte aggregation parameters slightly increased in NG, while the elongation index didn't show significant changes. Microcirculation was intact in the remnant kidney of NG. However, in comparison with SG, the diameter of glomeruli increased significantly (p < 0.01). CONCLUSIONS: Erythrocyte mass was influenced more than micro-rheological properties in this model. The main compensation mechanism was rather structural than at microcirculatory level.