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Biomedical subjects

K Mottaghy

Publications and source records attributed to K Mottaghy.

34 records · Page 2Linked to original sources

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↗

Gabexate mesilate (Foy) as an anticoagulant in extracorporeal circulation in dogs and sheep.

Gabexate mesilate (GM), a synthetic serine protease inhibitor with a short half-life time of approx. 80 sec, was applied as the exclusive anticoagulant in small scale extracorporeal circulation in narcotized dogs and sheep. The animals underwent a veno-venous bypass. As the blood was drawn out of the femoral vein, GM was infused immediately into the extracorporeal system. GM was greatly reduced because of its short half-life time before the blood reentered the animal via a brachial vein. In order to control the coagulatory state of the blood, the Activated Clotting Time (ACT), Partial Thromboplastine Time (PTT) and Recalcification Time (RT) were measured in regular intervals. In addition, a screen pressure test device was used to monitor on line during ECC the tendency of blood clotting. It was shown that the blood of the extracorporeal system was sufficiently anticoagulated by an infusion of 0.03 mg/ml/min GM. During two hours ECC, simultaneously measured ACT-values of the animals only differed up to 10 percent from the native values. Pilot studies have shown that the results of these model investigations could be successfully transferred to extracorporeal circulation with membrane oxygenators and pumps as they are clinically used.

Animals↗

Interfacial tension of some biological fluids: a comparative study.

In describing physiochemical properties of interfacial interactions, the interfacial tension is a major parameter. In the case of biological or body fluids, the presence of surface active substances influence the value of the surface tension. Thus, several proposals have been made for methods to investigate the changes in surface tension. Alterations of surface tension (compared to those of the normal values, e.g. of amniotic fluid) may indicate a pathophysiological status. This report presents data of systematically measured surface tensions of a few physiological fluids. Problems of methodology and data interpretation are discussed together with suggestions for new approaches, and comparisons are made with previously reported measurements.

Body Fluids↗

A new type of fluorocarbon liquid oxygenator.

A new oxygenator based on gas transfer across liquid-liquid interfaces (liquid oxygenator) is introduced. Perfluorinated chemicals are used as gas carriers. This liquid oxygenator differs from others in its concept basing on the dispersion of the blood droplets in an inert liquid by means of shear forces. This method allows high efficiency both with respect to saturation and to required blood flow. The results of gas transfer experiments in vitro and in vivo are satisfactory.

Animals↗

Application of surfaces with end point attached heparin to extracorporeal circulation with membrane lungs.

Application of heparin bonded surfaces (HBS) in the extracorporeal circuit (ECC) might avoid or at least reduce conventional heparin administration and would be of great benefit, especially in long-term perfusion. In this study, six sheep had a veno-venous bypass using membrane oxygenators with either total HBS or, in a control group, with untreated surfaces. Under strictly standardized conditions (body weight, drugs, geometry of tube, catheters, etc.), the animals in both groups received 300 IU/kg heparin before the catheterization as a bolus injection. In both groups, the measured heparin level decreased within 6 hours to zero, accompanied by a fall of other coagulation parameters (ACT, PTT etc.) to normal. In the control group, the ECC failed at this point because of clots in the oxygenators, whereas perfusions using HBS continued without further changes in clotting parameters until 12, 22, and 53 hours when the experiments were stopped intentionally. During the first 6 hours platelets showed a similar decrease in number in both groups and were comparable with conventional heparin treatment during further ECC periods. Other parameters, such as AT III, FXa, fibrinogen, and leukocytes were normal in both groups. The plasma hemoglobin increased markedly at the end of perfusion time in the control group but remained low even after 53 hours of ECC with HBS. The results indicate that the use of such completely heparin bonded systems can lead to a drastic reduction in systemic heparin administration.

Animals↗

Heparin free long-term extracorporeal circulation using bioactive surfaces.

As already shown, a single bolus injection of heparin is sufficient to perform extracorporeal circulation (ECC) for long-term lung support if bioactive surfaces (HBS) are used. In the present study whether complete avoidance of systemic heparinization using HBS is possible was studied. Seven conscious sheep (50-60 kg) underwent venovenous bypass under standardized conditions using a Maxima capillary membrane oxygenator. Drug administration, surgery, and other conditions, such as priming volume and blood flow rates, were identical in all experiments. All blood contacting surfaces (oxygenator, catheters, etc.) were HBS. The ECC periods were set for 24 hr (n = 3) and 5 days (n = 4). At no time was heparin administered. No complications occurred in any experiment. Partial thromboplastin time, activated clotting time, and other coagulation parameters remained within physiologic ranges. Platelets did not drop below 80% of baseline values, and hemolysis rates were negligible. Blood gas data and other vital parameters were normal during the entire ECC period. Results show that HBS can be applied to long-term ECC, without the necessity for heparin administration.

Animals↗

Technical aspects of plasma leakage prevention in microporous capillary membrane oxygenators.

A limiting factor in using microporous capillary membrane oxygenators (CMO) for long-term extracorporeal lung support is leakage. Application of heparin-coated CMO requires additional examination because leakage is probably caused by the temperature conditions of the gas, the blood and the circuit environment, and the surface tension phenomenon at the micropores. The authors designed a thermostatized box in which the temperature of flowing gas (Tg) and blood (Tb), and the interior temperature of the box (Ti) could be regulated independently. Tb was adjusted to the animal's body temperature, and Tg was kept about 2 degrees C higher to prevent condensation of the evaporated fluid from the blood side, through the micropores, into the gas phase. Ti was maintained between Tg and Tb. The saturated outlet gas could therefore condense only outside the box. This system was used during 5 days of venovenous bypass using a covalently heparin-bonded (Carmeda) CMO (Maxima, Medtronic) in four adult sheep. No plasma leakage occurred, the surface tension of condensate water remained constant, and the gas exchange capacity of CMO was unchanged.

Animals↗

A novel method for quantifying shape deformation applied to biocompatibility testing.

Cytotoxicity tests are important for the screening and evaluation of biocompatibility of artificial organs. Morphologic changes of cells that were contacted biomaterials or biomaterial extracts indicate their toxicity. However, information on cytotoxic effects is still obtained by subjective visual inspection of microscopic samples. In this article, a novel computer assisted method is introduced. The automatic analysis of digitized micrographs is achieved in several stages: segmentation, separation, classification, and measurement. The segmentation of the image is provided by a new local adaptive thresholding technique, which adapts the threshold window sizes onto local gray level distribution and yields optimal window sizes. The actual threshold is obtained by maximizing interclass variances and minimizing intraclass variance. For the separation of connected cells, the binarized samples are cleaned from "false" markers by morphologic filtering. The subsequent separation is a two phase approach. Information levels are generated top-down by successively applying an enhanced erosion operator, which yields markers and filters noise usually evolving from multiple erosions. The converse bottom-up integration of the eroded markers is performed by successively applying an enhanced dilation operator, which reconstructs the cells and prevents merging of already separated objects. The subsequent measuring provides quantitative parameters of the distribution of size and compactness of the cells contained within the sample. The method was evaluated by L-929 fibroblasts that were in contact with 0%, 5%, and 10% concentrations of ethanol. For each concentration, 268 images of the cell populations were captured. The obtained quantitative parameters are highly correlated to the common verbal description of morphologic changes. Therefore, the proposed automatic method has several advantages compared with subjective examinations. The results allow an objective comparison of the quantification of phenomena; the subjective influence of the observer is eliminated; and the laboratory staff is relieved of time consuming routine work.

Animals↗

Application of a new dynamic flow model for investigating the biocompatibility of modified surfaces.

An in vitro model was developed to compare the biocompatibility of four different coating methods (three heparin and one nonheparin) under hemodynamic conditions. Fresh human donor blood (heparin 5 IU/ml) was recirculated in a standardized experimental circuit. All circuit components were either coated or remained uncoated for control purposes. The aim of the study was to investigate a wide spectrum of effects on blood; coagulation parameters (e.g., fibrinogen, ATIII, thrombin-antithrombin-complex), complement parameters (C1rsC1 Inh, C3b(Bb)P, SC5b-9, C5a), differential blood analyses, platelet activation (flow cytometric investigations), PF 4, and PMN-elastase release were examined by showing possible trends. All heparin coated systems reduced platelet stimulation in comparison to untreated biomaterials. Leukocyte activation was reduced to different degrees depending upon the coating method used. Complement activation was markedly reduced by all coated systems. The results obtained indicate that the pump driven, dynamic blood flow model is suitable to characterize the biocompatibility of surface modified biomaterials. Advantages lie in the integration of the different polymers as parts of the circuit, the low priming volume, and the generation of blood flow conditions similar to those that occur in clinical applications.

Biocompatible Materials↗

Investigation on the ability of an ultrasound bubble detector to deliver size measurements of gaseous bubbles in fluid lines by using a glass bead model.

Detectors based on ultrasonic principles are today's state of the art devices to detect gaseous bubbles that may be present in extracorporeal circuits (ECC) for various reasons. Referring to theoretical considerations and other studies, it also seems possible to use this technology to measure the size of detected bubbles, thus offering the chance to evaluate their potential hazardous effect if introduced into a patient's circulation. Based on these considerations, a commercially available ultrasound bubble detector has been developed by Hatteland Instrumentering, Norway, to deliver bubble size measurements by means of supplementary software. This device consists of an ultrasound sensor that can be clamped onto the ECC tubing, and the necessary electronic equipment to amplify and rectify the received signals. It is supplemented by software that processes these signals and presents them as specific data. On the basis of our knowledge and experience with bubble detection by ultrasound technology, we believe it is particularly difficult to meet all the requirements for size measurements, especially if these are to be achieved by using a mathematical procedure rather than exact devices. Therefore, we tried to evaluate the quality of the offered bubble detector in measuring bubble sizes. After establishing a standardized test stand, including a roller pump and a temperature sensor, we performed several sets of experiments using the manufacturers software and a program specifically designed at our department for this purpose. The first set revealed that the manufacturer's recommended calibration material did not meet essential requirements as established by other authors. Having solved that problem, we could actually demonstrate that the ultrasonic field, as generated by the bubble detector, has been correctly calculated by the manufacturer. Simply, it is a field having the strongest reflecting region in the center, subsequently losing strength toward the ECC tubing's edge. The following set of experiments revealed that the supplementary software not only does not compensate for the ultrasonic field's inhomogeneity, but, furthermore, delivers results that are inappropriate to the applied calibration material. In the last set of experiments, we were able to demonstrate that the signals as recorded by the bubble detector heavily depend upon the circulating fluid's temperature, a fact that the manufacturer does not address. Therefore, it seems impossible to resolve all these sensor related problems by ever-increasing mathematical intervention. We believe it is more appropriate to develop a new kind of ultrasound device, free of these shortcomings. This seems to be particularly useful, because the problem of determining the size of gaseous bubbles in ECC is not yet solved.

Artificial Organs↗