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

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.

Has Extracorporeal Gas Exchange Performance Reached Its Peak?

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.

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.

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.

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.

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

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.

Inflow from a Cardiopulmonary Assist System to the Pulmonary Artery and Its Implications for Local Hemodynamics-a Computational Fluid Dynamics Study.

When returning blood to the pulmonary artery (PA), the inflow jet interferes with local hemodynamics. We investigated the consequences for several connection scenarios using transient computational fluid dynamics simulations. The PA was derived from CT data. Three aspects were varied: graft flow rate, anastomosis location, and inflow jet path length from anastomosis site to impingement on the PA wall. Lateral anastomosis locations caused abnormal flow distribution between the left and right PA. The central location provided near-physiological distribution but induced higher wall shear stress (WSS). All effects were most pronounced at high graft flows. A central location is beneficial regarding flow distribution, but the resulting high WSS might promote detachment of local thromboembolisms or influence the autonomic nervous innervation. Lateral locations, depending on jet path length, result in lower WSS at the cost of an unfavorable flow distribution that could promote pulmonary vasculature changes. Case-specific decisions and further research are necessary.

Computational fluid dynamics analysis of endoluminal aortic perfusion.

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.

Minimally Invasive Central Cannulation for Extracorporeal Life Support: The Uniportal and Subxiphoid Approach.

OBJECTIVE: Extracorporeal life support (ECLS) for circulatory and/or respiratory failure is improving. Currently, invasive sternotomies or rib-spreading thoracotomies are used for central cannulation of the heart and great vessels. Although peripheral cannulation of the extremities is often used, this approach may result in immobility and unintentional dislodgement. Less invasive methods for central cannulation are needed to achieve long-term ECLS. The objective of this study was to develop 2 different minimally invasive approaches for central thoracic cannulation. METHODS: Porcine hearts were positioned in a plastic thoracic model. An endoscopic camera and multiple endoscopic instruments were used. Both access points, uniportal (lateral) and subxiphoidal, were simulatively investigated. A novel cannulation method using purse string sutures, a custom-made endoscopic puncture tool, guidewires, and dilator-assisted cannulas was developed. Simulations were tested in a closed circuit regarding leak tightness. RESULTS: The uniportal approach allowed a cannulation of the aorta, inferior vena cava, right atrium, and main pulmonary artery. Cannulation of the right branches of the pulmonary artery and vein was also possible. From the subxiphoid approach, cannulation of the aorta, main pulmonary artery, and both atria were possible. Subsequent evaluation and leakage tests revealed no damage to the surrounding structures and tightly sealed cannulation sites. The uniportal approach was also successfully performed in a human cadaver to connect the aorta and right atrium with cannulas from the subxiphoidal space. CONCLUSIONS: Both uniportal and subxiphoid central cannulation of potential sites for ECLS were feasible. This study encourages further investigation and potential clinical translation of minimally invasive central organ support.

Efficacy of a Novel Medical Adhesive for Sealing Lung Parenchyma: An in vitro Study in Rabbit Lungs.

INTRODUCTION: During thoracic resection procedures, complete hemostasis and aerostasis are priorities. A persistent alveolar air leak is associated with increased morbidity and mortality rates. This study aimed to evaluate whether the novel medical adhesive VIVO (Adhesys Medical GmbH Aachen, Germany) is a reliable alternative sealing technique to routine surgical procedures. METHODS: We conducted an in vitro animal study by analyzing 21 lungs of New Zealand (n = 19) and Chinchilla Bastard (n = 2) rabbits (age, 11-18 weeks; weight, 2,400-3,600 g). Three groups, each comprising 7 animals, were evaluated. VIVO (VIVO-group) was compared with standard surgical lung parenchymal lesion closure with a polypropylene suture (Suture-group) and TachoSil® (TachoSil-group). We adopted a stable, pressure-controlled ventilation protocol. After explantation, a surgical incision 0.5-cm deep and 1.5-cm wide was made in the lungs using a customized template. Air leak was measured quantitatively (mL/min) using a respirator and visualized qualitatively by 2 observers who made independent judgments. Next, the leak was closed using VIVO, suture, or TachoSil® as specified by the manufacturer. Subsequently, positive end-expiratory pressure (PEEP) and inspiratory pressure were gradually increased until a maximum of 15 and 30 mbar were attained, respectively. RESULTS: At PEEPs of 8, 10, and 15 mbar, VIVO achieved complete sealing of the profound parenchymal defect in all (n = 7) lungs. After closure of the incision, we observed an air leak variation of 127 ± 114 mL/min (Suture-group), 31 ± 49 mL/min (VIVO-group), and 114 ± 134 mL/min (TachoSil-group). VIVO showed a significantly lower air leak than surgical sutures (p = 0.031) and TachoSil® (p = 0.046). CONCLUSION: VIVO offers sufficient closure of the lung parenchymal lesions. The novel adhesive enabled significantly better sealing with lower persistent air leakage than TachoSil® or surgical sutures. Further investigation using in vivo models is strongly encouraged to confirm our findings.

A New Percutaneous Approach to Treat Combined Right Ventricular and Respiratory Failure: The "Aachen Cannula".

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.