Brian J. Frankowski

Ex vivo testing of the intravenous membrane oxygenator.

Intravenous oxygenation represents a potential respiratory support modality for patients with acute respiratory failure or with acute exacerbations of chronic respiratory conditions. Our group has been developing an intravenous oxygenator, the IMO, which uses a constrained fiber bundle and a rapidly pulsating balloon within the fiber bundle. Balloon pulsation drives blood flow past the fibers at greater relative velocities than would otherwise exist within the host vessel, and gas exchange rates are enhanced. The purpose of this study was twofold: (1) to characterize the gas exchange performance of the current IMO in an extracorporeal mock vena cava vessel under conditions of known fixed vessel geometry and controlled blood flow rates; and (2) to compare the IMO gas exchange performance to that reported for the clinically tested IVOX device within a comparable ex vivo set-up. The ex vivo flow loop consisted of a 1 inch ID tube as a mock vena cava that was perfused directly from an anesthetized calf at blood flow rates ranging from 1 to 4 1/2 L/min. O2 and CO2 exchange rates were measured for balloon pulsation rates, which ranged from 0 to 180 bpm. Balloon pulsation significantly increased gas exchange, by 200-300% at the lowest blood flow rate and 50-100% at the highest blood flow rate. Balloon pulsation eliminated much if not all of the dependence of the gas exchange rate on blood flow rate as seen in passive oxygenators. This suggests that in clinical application the IMO may exhibit less gas transfer variability due to differences in cardiac output Over the entire flow rate range studied, the CO2 and O2 gas exchange rates of the IMO at maximal balloon pulsation varied from approximately 250 to 350 ml/min/m2. At maximum balloon pulsation the IMO exchanged CO2 and O2 at rates from 50-500% greater, depending upon the blood flow rate, than the exchange rates reported for the IVOX device in ex vivo tests.

Evaluation of a Pumping Assist Lung That Uses a Rotating Fiber Bundle

A paracorporeal respiratory assist lung (PRAL) is being developed for supplemental gas exchange to allow the native lungs of acute lung failure patients to heal. The device consists of a rotating annular microporous hollow fiber membrane bundle. The rotation augments the gas exchange efficiency of the device at constant flow-rate thereby uncoupling gas exchange and flow rate. The rotating fibers also enable the PRAL to pump the blood without the need for an additional pump or arterial cannulation. Blood flow rates will be between 500 and 750 ml/min with CO2 removal rates of 100–130 ml/min. A prototype was manufactured with an overall surface area of 0.25 m2. When rotated at 1500 rpm, CO2 removal increased by 133% and O2 transfer increased by 157% during an in vitro bovine blood study. The pumping of the rotating fiber bundle was assessed in a glycerol/water solution. At 1500 rpm, the PRAL generated 750 ml/min against 52 mm Hg pressure. Hemolysis of the device was assessed using in vitro bovine blood from a slaughterhouse. Plasma free hemoglobin levels were similar regardless of whether the rotating fibers were present in the PRAL, indicating that a rotating fiber bundle can be used to increase gas exchange without causing blood trauma.

Acute in vivo testing of an intravascular respiratory support catheter.

Current treatment for acute respiratory failure (ARF) includes the use of mechanical ventilation and/or extracorporeal membrane oxygenation, both of which can exacerbate lung injury. Intravenous respiratory support, using hollow fiber membranes placed in the vena cava, represents an attractive potential treatment for ARF, which could help reduce or eliminate ventilator induced trauma and/or other problems. Our group has been developing a respiratory support catheter (the Hattler catheter [HC]) that consists of a constrained hollow fiber bundle with a centrally located balloon. The balloon can be pulsated rapidly to increase blood flow across the fibers and decrease diffusional transfer resistance there, thus increasing gas exchange. The purpose of this study was to evaluate the HC in acute animal implants and to compare performance with that achieved in previous ex vivo studies. The HC was implanted into four calves by means of the external jugular vein and placed in the superior and inferior vena cava spanning the right atrium. Gas exchange, hemodynamics, and hematologic parameters were assessed over a range of balloon pulsation rates from 30 to 300 beats/minute. A <10% reduction in cardiac output was associated with catheter insertion and operation. The maximum CO2 exchange rate occurred at the highest pulsation rate and averaged 56 ± 3 ml/min, or 327 ± 15 ml/min per m2 when averaged to catheter membrane area, a level comparable to that achieved in the previous ex vivo studies. Balloon pulsation did not produce significant levels of hemolysis, as plasma-free hemoglobin remained below 10–15 mg/dl.

Acute In Vivo Testing of a Respiratory Assist Catheter: Implants in Calves Versus Sheep

A respiratory catheter that is inserted through a peripheral vein and placed within the vena cava is being developed for CO2 removal in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). The catheter uses a rapidly pulsating balloon to enhance gas exchange. In this study, the CO2 removal performance of our catheter was assessed in acute sheep implants and compared with calf implants, primarily because sheep have cardiac outputs (CO) that are more comparable with human CO and lower than calves. Respiratory catheters (25 mL balloon, 0.17 m2) were inserted acutely in sheep (n = 2) and calves (n = 6) through the jugular vein and placed within the vena cava in two positions: spanning the right atrium (RA) and within the inferior vena cava (IVC). The postinsertion CO in the sheep ranged from 4.1 to 7.2 L/min compared with 6.2 to 15.5 L/min for the calves. The maximum CO2 removal rates (vCO2) were 297 ml/min/m2 (calf) and 282 ml/min/m2 (sheep) in the RA position and 240 ml/min/m2 (calf) and 248 ml/min/m2 (sheep) in the IVC position. The respective removal rates between animal models were not statistically different (p values > 0 .05 for all data sets). The dependence of the vCO2 on balloon pulsation was also not statistically different between the animal models.

Evaluation of local gas exchange in a pulsating respiratory support catheter.

An intravenous respiratory support catheter, the next generation of artificial lungs, is being developed in our laboratory to potentially support acute respiratory failure or patients with chronic obstructive pulmonary disease with acute exacerbations. A rapidly pulsating 25 ml balloon inside a bundle of hollow fiber membranes facilitates supplemental oxygenation and CO2 removal. In this study, we hypothesized that nonuniform gas exchange in different regions of this fiber bundle was present because of asymmetric balloon collapse and the interaction of longitudinal flow. Four quarter regions and two rings around the central balloon were selectively perfused to evaluate local gas exchange in a 3.18 cm test section using helium as the sweep gas. Quarter region CO2 exchange rates at 400 beats per minute were 156.8 ± 0.8, 162.5 ± 1.8, 157.2 ± 0.2, and 196.6 ± 0.8 ml/min/m2 (top, front, bottom, and back, respectively). The back section, adjacent to convex balloon collapse, had 17–20% higher exchange than the other sections caused by higher relative velocities past its stationary fibers. Inner and outer ring maximum pulsation gas exchange rates were 174.4 ± 1.8 and 174.6 ± 0.9 ml/min/m2, respectively, showing that fluid flow was equally distributed throughout the fiber bundle.

Evaluation of fiber bundle rotation for enhancing gas exchange in a respiratory assist catheter.

Supplemental oxygenation and carbon dioxide removal through an intravenous respiratory assist catheter can be used as a means of treating patients with acute respiratory failure. We are beginning development efforts toward a new respiratory assist catheter with an insertional size <25F, which can be inserted percutaneously. In this study, we evaluated fiber bundle rotation as an improved mechanism for active mixing and enhanced gas exchange in intravenous respiratory assist catheters. Using a simple test apparatus of a rotating densely packed bundle of hollow fiber membranes, water and blood gas exchange levels were evaluated at various rotation speeds in a mock vena cava. At 12,000 RPM, maximum CO2 gas exchange rates were 449 and 523 mL/min per m2, water and blood, respectively, but the rate of increase with increasing rotation rate diminished beyond 7500 RPM. These levels of gas exchange efficiency are two- to threefold greater than achieved in our previous respiratory catheters using balloon pulsation for active mixing. In preliminary hemolysis tests, which monitored plasma-free hemoglobin levels in vitro over a period of 6 hours, we established that the rotating fiber bundle per se did not cause significant blood hemolysis compared with an intra-aortic balloon pump. Accordingly, fiber bundle rotation appears to be a potential mechanism for increasing gas exchange and reducing insertional size in respiratory catheters.

Evaluation of a respiratory assist catheter that uses an impeller within a hollow fiber membrane bundle.

Respiratory assist using an intravenous catheter may be a potential treatment for patients suffering from acute or acute-on-chronic lung failure. The objective of this study was to evaluate a novel respiratory catheter that uses an impeller within the fiber bundle to enhance gas exchange efficiency, thus requiring a smaller fiber bundle and insertional size (25 Fr) and permitting simple percutaneous insertion. Bench testing of gas exchange in deionized water was used to evaluate eight impeller designs. The three best performing impeller designs were evaluated in acute studies in four calves (122 ± 10 kg). Gas exchange increased significantly with increasing impeller rotation rate. The degree of enhancement varied with impeller geometry. The maximum gas exchange efficiency (exchange per unit surface area) for the catheter with the best performing impeller was 529 ± 20 ml CO2/min/m2 and 513 ± 21 ml CO2/min/m2 for bench and animal studies, respectively, at a rotation rate of 20,000 rpm. Absolute CO2 exchange was 37 and 36 ml CO2/min, respectively. Active mixing by rotating impellers produced 70% higher gas exchange efficiency than pulsating balloon catheters. The sensitivity of gas exchange to impeller design suggests that further improvements can be made by computational fluid dynamics-based optimization of the impeller.

Effect of impeller design and spacing on gas exchange in a percutaneous respiratory assist catheter.

Providing partial respiratory assistance by removing carbon dioxide (CO2 ) can improve clinical outcomes in patients suffering from acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. An intravenous respiratory assist device with a small (25 Fr) insertion diameter eliminates the complexity and potential complications associated with external blood circuitry and can be inserted by nonspecialized surgeons. The impeller percutaneous respiratory assist catheter (IPRAC) is a highly efficient CO2 removal device for percutaneous insertion to the vena cava via the right jugular or right femoral vein that utilizes an array of impellers rotating within a hollow-fiber membrane bundle to enhance gas exchange. The objective of this study was to evaluate the effects of new impeller designs and impeller spacing on gas exchange in the IPRAC using computational fluid dynamics (CFD) and in vitro deionized water gas exchange testing. A CFD gas exchange and flow model was developed to guide a progressive impeller design process. Six impeller blade geometries were designed and tested in vitro in an IPRAC device with 2- or 10-mm axial spacing and varying numbers of blades (2-5). The maximum CO2 removal efficiency (exchange per unit surface area) achieved was 573 ± 8 mL/min/m(2) (40.1 mL/min absolute). The gas exchange rate was found to be largely independent of blade design and number of blades for the impellers tested but increased significantly (5-10%) with reduced axial spacing allowing for additional shaft impellers (23 vs. 14). CFD gas exchange predictions were within 2-13% of experimental values and accurately predicted the relative improvement with impellers at 2- versus 10-mm axial spacing. The ability of CFD simulation to accurately forecast the effects of influential design parameters suggests it can be used to identify impeller traits that profoundly affect facilitated gas exchange.

Flow visualization study of a pulsating respiratory assist catheter

Our group is currently developing an intravenous respiratory assist device that uses a centrally located pulsatile balloon within a hollow fiber bundle to enhance gas exchange rate via active mixing mechanism. We tested the hypothesis that the nonsymmetric inflation and deflation of the balloon lead to both nonuniform balloon-generated secondary flow and nonuniform gas exchange rate in the fiber bundle. The respiratory catheter was placed in a 1-in. internal diameter rigid test section of an in vitro flow loop (3 L/min deionized water). Particle image velocimetry (PIV), which was used to map the velocity vector field in the lateral cross-section, showed that the balloon pulsation generated a nonuniform fluid flow surrounding the respiratory assist catheter. PIV was also used to characterize the fiber bundle movement, which was induced by the balloon pulsation. Gas permeability coefficient of the device was evaluated by using both the fluid velocity and the relative velocity between the fluid and the fiber bundle. The highest difference in the gas permeability coefficient predicted by using the relative velocity was about 17% to 23% (angular direction), which was more uniform than the 49% to 59% variation predicted by using the fluid velocity. The movement of the fiber bundle was responsible for reducing the variation in the fluid velocity passing through the bundle and for minimizing the nonuniformity of the gas permeability coefficient of the respiratory assist catheter.

Fiber Bundle Design for an Integrated Wearable Artificial Lung

Mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) are the only viable treatment options for lung failure patients at the end-stage, including acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). These treatments, however, are associated with high morbidity and mortality because of long wait times for lung transplant. Contemporary clinical literature has shown ambulation improves post-transplant outcomes in lung failure patients. Given this, we are developing the Pittsburgh Ambulatory Assist Lung (PAAL), a truly wearable artificial lung that allows for ambulation. In this study, we targeted 180 ml/min oxygenation and determined the form factor for a hollow fiber membrane (HFM) bundle for the PAAL. Based on a previously published mass transfer correlation, we modeled oxygenation efficiency as a function of fiber bundle diameter. Three benchmark fiber bundles were fabricated to validate the model through in vitro blood gas exchange at blood flow rates from 1 to 4 L/min according to ASTM standards. We used the model to determine a final design, which was characterized in vitro through a gas exchange as well as a hemolysis study at 3.5 L/min. The percent difference between model predictions and experiment for the benchmark bundles ranged from 3% to 17.5% at the flow rates tested. Using the model, we predicted a 1.75 in diameter bundle with 0.65 m2 surface area would produce 180 ml/min at 3.5 L/min blood flow rate. The oxygenation efficiency was 278 ml/min/m2 and the Normalized Index of Hemolysis (NIH) was less than 0.05 g/100 L. Future work involves integrating this bundle into the PAAL for which an experimental prototype is under development in our laboratory.