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Biomedical subjects

K Mottaghy

Publications and source records attributed to K Mottaghy.

At least 19 recordsLinked to original sources
PubMed2003

Application of Taylor vortices in hemocompatibility investigations.

BACKGROUND: Artificial organs, implants and extracorporeal circulation affect the physiological flow characteristics of blood as a liquid organ. These artificial systems consist of a wide variety of biomaterials with different geometries and, therefore, with their own flow properties. Secondary flow also occurs in extra--as well as in intracorporeal circulation. METHODS: In order to investigate the influence of vortical flow conditions a modified Taylor-Couette system was introduced. It consisted of two coaxial cylinders whose surfaces were the target of investigation. The annular gap was filled with donor blood shear and secondary flows were produced by rotating the inner cylinder. Platelet activation and protein adsorption were investigated as markers for thrombogenicity. RESULTS: At shear rates high enough to establish stable Taylor vortices (G > or = 550 s(-1)) significant differences between vortical Taylor flow and steady laminar flow were detected. At shear rates of G > or = 550 s(-1) laminar flow caused a significantly higher platelet drop and PF4 release when compared to Taylor vortex flow. Also protein adsorption per square unit was significantly higher for laminar flow. CONCLUSIONS: Based on the present data we conclude that vortical flow patterns lead to an accumulation of platelets and plasma proteins in the vortex center and therefore to a decreased probability of contact between platelets and material surfaces. It can be concluded that a preactivation of the platelets circulating in extracorporeal circuits can be manifested downstream in other geometrical configurations and flow conditions.

Adsorption↗
PubMed2002

In vitro blood damage by high shear flow: human versus porcine blood.

Devices for modern heart support are minimized to reduce priming blood volume and contact area with foreign surfaces. Their flow fields are partly governed by very high velocity gradients. In order to investigate blood damage, porcine and human blood was passed through a narrow Couette type shear gap applying defined high shear rates within the typical range for devices such as blood pumps or artificial heart valves (gamma = 1800/s to 110,000/s for 400 ms). Traumatization profiles of both blood species were recorded in terms of hemolysis and platelet count. Sublethal damage in terms of platelet (PF4) and complement activation (C5a) was additionally measured for human blood. Results for porcine and human blood were very similar. Hemolysis was not started until critical shear rates of about 80,000/s. Impact on platelets was severe with drops in cell count of up to 65% (at gamma = 55,000/s to 110,000/s) likely to set stronger limits to the design layout of devices than hemolysis. Concentrations of PF4 and C5a clearly increased with shear rate exhibiting stronger gradients where hemolysis started. Due to the similar results of porcine and human blood for hemolysis and platelet drop, porcine blood seems to be suitable for device testing. Selection of blood species would thus depend on handling, availability and analysis demands.

Animals↗
PubMed2000

Scale-independent shape analysis for quantitative cytology using mathematical morphology.

A system for automatic quantification of morphological changes of cell lines, proposed for cytotoxicity tests of biomaterials, is presented. Light-micrographs of cultured cells are segmented by adaptive thresholding within a local adaptive window. Connected cells in binarized micrographs are separated by a novel morphological multiscale method, treating cells in their size-specific scale and hence resulting in scale-independent separations. Significant shape descriptors correlating well with cell toxicity are extracted from single cells. Size and compactness distributions turned out to be reliable and useful parameters, providing an alternative to the common subjective grading of shape deformations by visual inspection. The system is evaluated for several standardized toxical reference substances and is now in use for clinical biocompatibility testing.

Cell Line↗
PubMed2000

In vitro validation of gastric air tonometry using perfluorocarbon FC 43 and 0.9% sodium chloride.

Monitoring splanchnic perfusion by means of gastric intramucosal tonometry is carried out using saline, or more recently, air tonometry using the Tonocap. The objective of this study was the validation of the Tonocap in saline and perfluorocarbon FC 43. The two methods underestimated the predefined PCO2 value by an average of 10%, with clinically acceptable precision. Accuracy of the Tonocap improved at high PCO2 values (9.33 and 9.94 kPa), whereas saline tonometry was superior at low PCO2 values (3.99 and 3.75 kPa). The Tonocap provides a fast and reliable estimation of the PCO2, and with the revised software requiring only 10 min of equilibration, will increase the comparability of future studies.

Fluorocarbons↗
PubMed2000

C1 inhibitor prevents capillary leakage after thermal trauma.

OBJECTIVE: In burned patients, activation of the complement and clotting systems is suggested to play an important role in the development of the capillary leak syndrome and inflammatory tissue destruction. In an animal model of thermal trauma, the possible protective effect of C1 inhibitor (C1Inh), a major control protein of both the complement and clotting systems, was investigated. DESIGN: Prospective, controlled study. SETTING: Animal model. SUBJECTS: Healthy pigs weighing 30 kg. INTERVENTIONS: Pigs were scalded for 25 secs with 75 degrees C hot water to achieve a 30% total body surface deep partial-thickness burn. The treatment group (n = 8) received C1Inh concentrate at an initial dose of 100 units/kg body weight immediately after thermal trauma, followed by three further applications every 12 hrs. Two control groups included animals that were either scalded (n = 8) or not scalded (n = 7) and treated with lactated Ringer's solution. MEASUREMENTS: Before and at various time points after trauma blood samples were analyzed for complement activation (APH50, CH50, SC5b-9, C3). Continuous monitoring of hemodynamic variables was performed and postmortem histologic examination of specimens from lung, heart, liver, kidney, stomach, duodenum, jejunum, ileum, and colon was carried out. Aseptically collected mesenteric lymph nodes were pooled and screened for bacterial translocation. For evaluation of the burn wound, biopsies from defined scalded and not scalded areas were taken daily. As a measure for edema formation, the weight of the animals was recorded every 2 hrs. RESULTS: After C1Inh treatment, which led to a significantly reduced complement activation, the clinical outcome was clearly improved, as indicated by vital signs and as demonstrated by reduced edema formation. Treated animals presented a diminished bacterial translocation. Pathologic alterations were clearly diminished in the burned skin, in shock-related organs, and in the intestines. CONCLUSION: Application of C1Inh appears to be an effective means to prevent capillary leakage and inflammatory tissue destruction after thermal trauma.

Animals↗
PubMed1998

The therapeutic effect of C1-inhibitor on gut-derived bacterial translocation after thermal injury.

To test the effects of C1-esterase inhibitor in scald burns on bacterial translocation and intestinal damage, standardized deep partial-thickness burns were inflicted on domestic pigs, scalding 30% of the skin surface for 25 s with 75 degrees C hot water. The animals (n = 17; weight 25-35 kg) were divided into three groups: I) the control group (n = 5) without scald burn; II) the group (n = 6) with scald burn; and III) the group with C1-inhibitor (n = 6): scald burn and treatment with C1-inhibitor (C1-INH; BERINERT, Behring, Marburg, Germany). Parameters measured and compared in this model were activity of complement system, hemodynamics, body weight, pathological organ alterations including intestinal lesions, bacterial translocation, and skin damage. C1-INH administration significantly decreased the plasma levels of the specific soluble membrane attack complex (SC5b-9), bacterial translocation, and the degree of intestinal ischemia in the postburn period compared with untreated animals. Moreover, animals treated with C1-INH exhibited a minor degree of organ alterations including damage of the skin and development of edema. The favorable effects of C1-INH may be explained by the protection of the intestinal and dermal microcirculation in the acute phase of thermal injury.

Animals↗
PubMed1996

[Determining the effectiveness of percutaneous cava filters: experimental studies].

PURPOSE: In vitro clot-trapping capacity of 16 different caval filters should be evaluated under varying experimental conditions. MATERIAL AND METHODS: In a flow model simulating in vivo conditions (soft latex tube, dextran solution at 37 degrees C, pulsatile flow at a mean rate of 3 1/min) the efficiency of 16 caval filters was evaluated in horizontal and vertical position by using 640 or 1280 clots/filter (8 sizes). Non-self centering filters were tested in centric and in tilted position. RESULTS: Efficiency of optimally centered caval filters varied between 97.8 and 69.4%. The largest thrombi were captured by all optimal centered filters. A change from vertical to horizontal position of the flow model resulted in a variation of filter efficiency by about 4.8%. Efficiency of non-self centering filters decreased significantly when placed in a tilted position (mean decrease 15.5%; range 2.7%-37.7%) resulting in a deterioration of the capture rate by as much as 43.2%. CONCLUSION: Under optimal study conditions efficiency of all evaluated caval filters was high. Tilting of caval filters resulted in a significant efficiency decrease.

Animals↗
PubMed1993

Extracorporeal circulation: in vivo and in vitro analysis of complement activation by heparin-bonded surfaces.

Complement activation was analyzed during extracorporeal CO2 removal to compare heparin-coated with standard surfaces where systemic heparinization was required. In vivo studies were performed in adult sheep for up to 5 days under standardized conditions using a capillary membrane oxygenator. Applying assays for hemolytic complement function (CH50, APH50) and C3-derived split products, we found that complement activation was markedly reduced in sheep connected to an extracorporeal circuit where heparin was covalently bound by end-point attachment. In addition, incubation of human serum in a miniaturized circulation system revealed less complement activation by heparin-bonded surfaces, as evaluated by enzyme-linked immunosorbent assays for C3a and the activation-specific protein-protein complexes, C1rsC1 inhibitor (classical pathway) and C3b(Bb)P (alternative pathway). Our results provide further evidence that biocompatibility can be improved by end-point attachment of heparin to the surfaces of the extracorporeal circuit.

Animals↗
PubMed1992

Progress in veno-venous long-term bypass techniques for the treatment of ARDS. Controlled clinical trial with the heparin-coated bypass circuit.

Extracorporeal CO2 removal combined with low-frequency positive pressure ventilation (ECCO2-R LFPPV) is a new therapeutic approach in treatment of ARDS. The main problem during long-term extracorporeal support is anticoagulation and related bleeding problems. We conducted a prospective, randomized and controlled clinical trial in 18 patients to compare the effect of the non-heparin-coated (Scimed = group 1) with the heparin-coated (Carmeda = group 2) extracorporeal circuit on clinical course and complication rate. In group 2 the daily blood loss, the amount of substituted red cells and the i.v. heparin dose were significantly lower than in group 1. Bleeding complications were less and more patients survived in group 2. The disadvantage of the hollow fiber oxygenators in the heparin-coated system was plasma leakage, which was more frequent in patients with pancreatitis and hyperbilirubinemia.

Adolescent↗
PubMed1991

Right ventricular function assessed by thermodilution technique during apnea and mechanical ventilation.

OBJECTIVES: To evaluate strategies for thermodilution-based measurement of cardiac output and right ventricular (RV) ejection fraction and to assess the effects of controlled mechanical ventilation in patients. Furthermore, to compare strategy-associated reproducibility with reference values obtained during long-term apnea. DESIGN: Crossover trial in patients; reference values from apneic animals. SETTING: University ICU and physiology laboratory. PATIENTS: Six consecutive male ICU patients (48 to 70 yrs) after major abdominal vascular surgery. ANIMALS: two adult female sheep. INTERVENTIONS: Three ventilatory rates (8, 16, and 24 cycles/min) and 15-sec periods of apnea were selected for measurements in patients. In animals, continuous apnea was achieved with extracorporeal CO2 removal and apneic oxygenation. MEASUREMENTS: Measurements were performed using an appropriate pulmonary artery catheter and an ejection fraction/cardiac output computer prototype. The thermal indicator was injected automatically at four defined points of the ventilatory cycle, but triggered manually during apnea. MAIN RESULTS: At 8 cycles/min, there was a wide mean range of cyclic variable modulation, with a coefficient of variation of 11.6% and 23.2% for cardiac output and RV ejection fraction, respectively. Allowing for ventilatory phase or changing from 8 to 16 cycles/min reduced errors by half. Combining both procedures resulted in a coefficient of variation of 4.7% and 6.6% for cardiac output and RV ejection fraction, respectively. The best coefficient of variation values obtained during 15 secs of apnea in patients approached those variations in experimental apnea (coefficient of variation of 2.1% and 4.5% for cardiac output and RV ejection fraction, respectively). CONCLUSIONS: At low ventilatory rates, best results are achieved by averaging four phase-selected measurements. One-point measurements were less accurate and random point measurements less reproducible.

Aged↗
PubMed1991

In vivo demonstration of the Haldane effect during extracorporeal gas exchange.

During the extracorporeal support (LFPPV-ECCO2R) of 11 patients suffering from severe lung failure (ARDS), we consistently noticed a higher arterial than mixed-venous PCO2 in blood samples drawn at the same time. Two explanations are possible: a) the Haldane effect (HE), b) CO2 from lung tissue metabolism. In order to distinguish changes in PCO2 due to the HE from those due to tissue CO2 production, CO2 content (CCO2) was calculated. The results were compared to animal experiments with hyperoxic apnea, after which arterial and mixed-venous samples were drawn simultaneously. All blood gas samples were analyzed for pH, PCO2, PO2, and O2-saturation, from which CCO2 was calculated. In both groups, PaCO2 was 2.15 mmHg (2.7 mmHg respectively) higher at a lower CaCO2 (-2.87 ml/l, -14.9 ml/l). Oxygen saturation increased by 8.1% in the human group and 17.8% in the animal group. A significant relationship was found between changes in PCO2 and changes in O2-saturation. This is a demonstration of the Haldane effect.

Animals↗
PubMed1991

Heparin-coated versus non-coated surfaces for extracorporeal circulation.

Studies were made to compare completely heparin-bonded (HBS) and conventional extracorporeal circulation surfaces using capillary membrane oxygenators (CMO) in sheep and dogs for up to five days. The aims were: to investigate the need for systemic heparinization in the case of heparin-coated surfaces, to assess blood compatibility and gas exchange performance of both systems and the extent of complement activation, and to find solutions for plasma leakage by the use of CMO. All studies were performed under standardized conditions, such as drugs, surgery, priming, blood flow rate etc. For heparin-coated surface studies all blood interfaces (CMO, catheters, tubes, etc) were coated. It was possible to eliminate systemic heparinization totally when HBS were used. During the five-day non-heparin application period blood coagulation parameters were almost unchanged and in the physiological range, platelets did not drop below 80%, hemolysis was negligible and gas exchange performance was unaffected. Less complement activation occurred with HBS than with non-coated surfaces.

Animals↗
PubMed1990

Effect of long-term hypoxia on oxygen transport properties of blood in pregnant guinea pigs.

Pregnant guinea pigs undergoing long-term hypoxia were studied and the results compared with those of control animals (pregnant, but non-hypoxic). Hypoxic animals demonstrated a decrease of O2 affinity (-7%) and an increase of O2 capacity (+35%). In addition, the HCT was found to be higher in the hypoxic group (+41%), causing haemorheological disadvantages; in a shear model study the blood of hypoxic animals had to be exposed to the gas compartment of the rheo-oxymeter up to 62% longer than that of the control group. We have postulated, that this rheological impairement is compensated, since no abnormalities in number and abortion rate of fetuses (due to a possible O2 delivery impairment) were found. Our morphological studies in fact support this opinion, showing e.g. more capillary branchings and loops and a reduction of diffusion distances between maternal and fetal blood in hypoxic guinea pig placentae. The results emphasize the importance of more detailed rheological studies in connection with other investigations for a complete description of compensatory mechanisms.

Animals↗
PubMed1990

Alterations of the fetal capillary bed in the guinea pig placenta following long-term hypoxia.

Oxygen supply is an important regulator of the fetal placental capillarization. To determine the effects of long-term hypoxia on the fetal placental vessel arrangement pregnant guinea pigs were kept under hypoxic conditions (12% O2 for 45 days). Vessel casts showed a significant difference in branching and orientation of the vessels between the controls and the hypoxic animals. The hypoxic group had a less orientated capillary bed with increased branching and coiling. By light- and transmission electron microscopical studies, there was a decreased diffusion distance, a decreased diameter of the fetal capillaries, and an increased number of capillary cross-sections. These results are consistent with the hypothesis that chronic hypoxia is responsible for increased branching and coiling of the capillaries resulting in a dense network of short and narrow capillaries in the placenta.

Animals↗
PubMed1985

Extracorporeal CO2-removal: pulmonary and extracorporeal equilibria in dogs and sheep.

Extracorporeal CO2-removal promises to be an efficient alternative to the conservative treatment of advanced lung diseases. Extracorporeal CO2-removal is achieved in a veno-venous bypass in combination with low frequency ventilation. Positive clinical results in the treatment of adult respiratory distress syndrome (ARDS) are encouraging. In order to prove the applicability of this method to different kinds of respiratory insufficiency, physiological studies using animal models are necessary. We report here on experiments with dogs and sheep undergoing a veno-venous bypass employing a CO2-eliminator. The experimental results are compared with theoretical values which predict the important relationships between blood flow rate of the extracorporeal circulation (ECC), the CO2-elimination capacity of the CO2-eliminator and the low ventilation rate (down to apnea for 5 h) of the natural lung. It was shown that the blood gas data as well as acid base status could be maintained within physiological ranges.

Animals↗