FHFlutura Hima

Flutura Hima

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Previous Organizations / Institutes

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Flutura Hima has a total of 32 co-authors. Here are the top co-authors by number of shared publications:


Latest Publications

  • Open Access

    Molecular Hydrogen and Extracorporeal Gas Exchange: A Match Made in Heaven? An In Vitro Pilot Study

    by Foivos Leonidas Mouzakis, Flutura Hima, Ali Kashefi, Johannes Greven, Lothar Rink, Emiel P. C. van der Vorst, Joachim Jankowski, Khosrow Mottaghy, Jan Spillner

    Extracorporeal circulation (ECC) is frequently implemented in a vast array of modalities such as hemodialysis, cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), and others. Patients receiving any such therapy are frequently encumbered with chronic inflammation, which is inherently accompanied by oxidative stress. However, ECC treatments themselves are also responsible for sustaining or promoting inflammation. On these grounds, an in vitro study was designed to investigate the therapeutic potential of molecular hydrogen (H2) against pro-inflammatory agents in ECC settings. Five miniature ECMO circuits and a small vial (Control) were primed with heparinized blood from healthy adult donors (n = 7). Three of the ECMO systems were injected with lipopolysaccharide (LPS), out of which one was additionally treated with an H2 gas mixture. After 6 h, samples were drawn for the assessment of specific biomarkers (MCP-1, MPO, MDA-a, TRX1, and IL-6). Preliminary results indicate a progressive oxidative and inflammatory response between the six systems. Circulation has triggered inflammation and blood trauma, but the staggering influence of LPS in this outcome is indisputable. Accordingly, hydrogen’s remedial potential becomes immediately apparent as biomarker concentrations tend to be lower in the H2-handled circuit. Future research should have distinct objectives (e.g., dosage/duration/cycle of hydrogen administration) in order to ascertain the optimal protocol for patient treatment.


  • Open Access

    Has Extracorporeal Gas Exchange Performance Reached Its Peak?

    by Foivos Leonidas Mouzakis, Ali Kashefi, Flutura Hima, Khosrow Mottaghy, Jan Spillner

    Extracorporeal gas exchange therapies evolved considerably within the first three–four decades of their appearance, and have since reached a mature stage, where minor alterations and discrete fine-tuning might offer some incremental improvement. A different approach is introduced here, making use of modern, purely diffusive membrane materials, and taking advantage of the elevated concentration gradient ensuing from gas pressure buildup in the gas chamber of the oxygenator. An assortment of silicone membrane gas exchangers were tested in vitro as per a modified protocol in pursuance of assessing their gas exchange efficiency under both regular and high-pressure aeration conditions. The findings point to a stark performance gain when pressurization of the gas compartment is involved; a 40% rise above atmospheric pressure elevates oxygen transfer rate (OTR) by nearly 30%. Carbon dioxide transfer rate (CTR) does not benefit as much from this principle, yet it retains a competitive edge when higher gas flow/blood flow ratios are employed. Moreover, implementation of purely diffusive membranes warrants a bubble-free circulation. Further optimization of the introduced method ought to pave the way for in vivo animal trials, which in turn may potentially unveil new realms of gas exchange performance for therapies associated with extracorporeal circulation.


  • A new approach towards extracorporeal gas exchange and first in vitro results

    by Foivos Leonidas Mouzakis, Ali Kashefi, Jan Spillner, Stephan Rütten, Khosrow Mottaghy, Flutura Hima

    Objectives: Extracorporeal life support (ECLS) pertains to therapeutic and prophylactic techniques utilized in a wide range of medical applications, with severe pulmonary diseases being the most prominent cases. Over the past decades, little progress has been made in advancing the basic principles and properties of gas exchangers. Here, in an unconventional approach, dialysis hollow fibers are handled with silicone to create a purely diffusive coating that prevents plasma leakage and promotes gas exchange. Methods: Commercial dialyzers of varying surface area and fiber diameter have been coated with silicone, to determine the impact of each parameter on performance. The impermeability of the silicone layer has been validated by pressurization and imaging methods. SEM images have revealed a homogeneous silicone film coating the lumen of the capillaries, while fluid dynamic investigations have confirmed its purely diffusive nature. Results: The hemodynamic behavior and the gas exchange efficiency of the silicone-coated prototypes have been investigated in vitro with porcine blood under various operating conditions. Their performance has been found to be similar to that of a commercial PMP oxygenator. Conclusions: This novel class of gas exchangers is characterized by high versatility and expeditious manufacturing. Intraoperability between conventional ECLS systems and dialysis machines broadens the range of application infinitely. Ultimately, long-term clinical applicability ought to be determined over in vivo animal investigations.


  • Open Access

    Blood Gas Parameters and Acid–Base Balance during Extracorporeal Lung Support with Oxygenators: Semi-Empirical Evaluation

    by Lal Babu Khadka, Foivos Leonidas Mouzakis, Ali Kashefi, Flutura Hima, Jan Wilhelm Spillner, Khosrow Mottaghy

    Membrane artificial lungs (oxygenators) are used in cardiopulmonary surgery as well as, in some cases, in severe lung disease to support the natural lung by means of ECMO (extracorporeal membrane oxygenation). The oxygen and carbon dioxide transfer rates of any oxygenator are usually assessed by considering several blood gas parameters, such as oxygen saturation, hemoglobin concentration, partial pressure of oxygen and carbon dioxide, bicarbonate concentration, and pH. Here, we report a set of semi-empirical equations that calculate such parameters directly from their partial pressures and assess the acid–base balance during ECMO. The implementation of this equation set permits the evaluation of any oxygenator, existing or prototypes in development, as well as the development of clinical decision-making tools for predicting the blood gas state and acid–base balance during surgical interventions and ECMO. The predicted results are then compared with experimental data obtained from in vitro gas exchange investigations with a commercial oxygenator using fresh porcine blood. The high correlation, R2>0.95, between the predicted and the experimental data suggests a possibility of using such empirical equations in the simulation of gas transfer in a cardiopulmonary system with an oxygenator for any venous inlet blood gas data and also for estimating the acid–base balance during such therapy.


  • Open Access

    In vitro evaluation of the performance of an oxygenator depending on the non-standard gas content of the inlet blood with special regard on CO2 elimination

    by Flutura Hima, Amalia Saunders, Ali Kashefi, Foivos Mouzakis, Khosrow Mottaghy, Jan Spillner, Rachad Zayat, Sebastian Kalverkamp

    Introduction: The performance of an oxygenator, as found in literature, is evaluated according to protocols that define standard values of the gas content in the inlet blood. However, when dealing with simulations of lung insufficiency, a more extensive evaluation is needed. This work aims to investigate and assess the gas exchange performance of an oxygenator for different input values of gas content in blood. Methods: Three commercially available oxygenators with different membrane surfaces were investigated in a mock loop for three blood flow rates (0.5l/min, 1l/min, and 5l/min) and two gas-to-blood ratios (1:1, and 15:1). The initial CO2 and O2 partial pressures (pCO2 and pO2) in blood were set to ≥ 100 mmHg and ≤10 mmHg, respectively. For each ratio, the efficiency, defined as the ratio between the difference of pressure inlet and outlet and the inlet pCO2 (pCO2(i)), was calculated. Results: The CO2 elimination in an oxygenator was higher for higher pCO2(i). While for a pCO2(i) of 100 mmHg, an oxygenator eliminated 80 mmHg, the same oxygenator at the same conditions eliminated 5 mmHg CO2 when pCO2(i) was 10 mmHg. The efficiency of the oxygenator decreased from 76,9% to 49,5%. For simulation reasons, the relation between the pCO2(i) and outlet (pCO2(o)) for each oxygenator at different blood and gas flows, was described as an exponential formula. Conclusion: The performance of an oxygenator in terms of CO2 elimination depends not only on the blood and gas flow, but also on the initial pCO2 value. This dependence is crucial for simulation studies in the future.


  • Open Access

    Oxygenation performance assessment of an artificial lung in different central anatomic configurations

    by Flutura Hima, Sebastian Kalverkamp, Ali Kashefi, Khosrow Mottaghy, Rachad Zayat, Lasse Strudthoff, Jan Spillner, Foivos Mouzakis

    Objectives: Aim of this work was to characterize possible central anatomical configurations in which a future artificial lung (AL) could be connected, in terms of oxygenation performance. Methods: Pulmonary and systemic circulations were simulated using a numerical and an in vitro approach. The in vitro simulation was carried out in a mock loop in three phases: (1) normal lung, (2) pulmonary shunt (50% and 100%), and (3) oxygenator support in three anatomical configurations: right atrium-pulmonary artery (RA-PA), pulmonary artery-left atrium (PA-LA), and aorta-left atrium (Ao-LA). The numerical simulation was performed for the oxygenator support phase. The oxygen saturation (SO2) of the arterial blood was plotted over time for two percentages of pulmonary shunt and three blood flow rates through the oxygenator. Results: During the pulmonary shunt phase, SO2 reached a steady state value (of 68% for a 50% shunt and of nearly 0% for a 100% shunt) 20 min after the shunt was set. During the oxygenator support phase, physiological values of SO2 were reached for RA-PA and PA-LA, in case of a 50% pulmonary shunt. For the same conditions, Ao-LA could reach a maximum SO2 of nearly 60%. Numerical results were congruous to the in vitro simulation ones. Conclusions: Both in vitro and numerical simulations were able to properly characterize oxygenation properties of a future AL depending on its placement. Different anatomical configurations perform differently in terms of oxygenation. Right to right and right to left connections perform better than left to left ones.


  • Open Access

    Computational fluid dynamics analysis of endoluminal aortic perfusion

    by Daniel Malinowski, Yvan Fournier, Andreas Horbach, Michael Frick, Mirko Magliani, Sebastian Kalverkamp, Martin Hildinger, Jan Spillner, Mehdi Behbahani, Flutura Hima

    Introduction: In peripheral percutaneous (VA) extracorporeal membrane oxygenation (ECMO) procedures the femoral arteries perfusion route has inherent disadvantages regarding poor upper body perfusion due to watershed. With the advent of new long flexible cannulas an advancement of the tip up to the ascending aorta has become feasible. To investigate the impact of such long endoluminal cannulas on upper body perfusion, a Computational Fluid Dynamics (CFD) study was performed considering different support levels and three cannula positions. Methods: An idealized literature-based- and a real patient proximal aortic geometry including an endoluminal cannula were constructed. The blood flow was considered continuous. Oxygen saturation was set to 80% for the blood coming from the heart and to 100% for the blood leaving the cannula. 50% and 90% venoarterial support levels from the total blood flow rate of 6 l/min were investigated for three different positions of the cannula in the aortic arch. Results: For both geometries, the placement of the cannula in the ascending aorta led to a superior oxygenation of all aortic blood vessels except for the left coronary artery. Cannula placements at the aortic arch and descending aorta could support supra-aortic arteries, but not the coronary arteries. All positions were able to support all branches with saturated blood at 90% flow volume. Conclusions: In accordance with clinical observations CFD analysis reveals, that retrograde advancement of a long endoluminal cannula can considerably improve the oxygenation of the upper body and lead to oxygen saturation distributions similar to those of a central cannulation.


  • A New Percutaneous Approach to Treat Combined Right Ventricular and Respiratory Failure: The “Aachen Cannula”

    by Flutura Hima, Marjolijn Gümmer, Andreas Prescher, Bader Altarawneh, Rachad Zayat, Nima Hatam, Lisa Ernst, Sebastian Kalverkamp, Jan Spillner, Jessica Arias-Pinilla

    Introduction: Right ventricular failure (RVF) on its own is a life-threatening condition. Often it manifests as a two-organ failure in the final phase of several lung diseases. Mechanical circulatory support is a proven treatment of RVF but remains challenging. Our objective is to develop a novel, simplified, and minimally invasive cannula approach to treat both RVF and respiratory failure. Methods: We conceptualized a dual lumen cannula approach to allow oxygenated right-to-left shunting at an atrial level to decompress right-sided circulation. A minimally invasive approach through percutaneous, transjugular insertion and transseptal placement should enable patients to be non-sedated and even ambulatory. In an iterative design, pre-prototyping, prototyping, and anatomic fitting process, such a cannula was generated and tested in both cadaveric and fluid dynamic studies. Results: After various modifications and improvements, a 27-Fr 255-mm-long double-lumen cannula with an inner line (oxygenated blood return to patient into the left atrium) of 18 Fr and an inflatable balloon (with a volume of approximately 1 mL) at the outflow tip was produced – one version with a straight head and another one with a curved head. In our anatomic studies, the “Aachen Cannula” allowed an easy transjugular introduction and advancement into the right atrium by Seldinger technique. Transseptal placement was achieved by puncture (Brockenbrough needle) in combination with dilatation and was then secured in place with the stabilizing balloon, even under slight tension. The cannula prototype enabled a flow of up to 3.5 L/min, at which common pressure drops were observed. Conclusion: In conclusion, we successfully conceptualized, designed, and verified a minimally invasive one-cannula approach for the treatment of either isolated right heart failure and even combined RVF and respiratory failure through our transseptal Aachen Cannula. This concept may also be carried out in ambulatory conditions. Moreover, this approach completely avoids recirculation issues and ensures reliable oxygenated coronary as well as cerebral perfusion.