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.

Blood biocompatibility assessment of an intravenous gas exchange device.

To treat acute lung failure, an intravenous membrane gas exchange device, the Hattler Catheter, is currently under development. Several methods were employed to evaluate the biocompatibility of the device during preclinical testing in bovines, and potential coatings for the fibers comprising the device were screened for their effectiveness in reducing thrombus deposition in vitro. Flow cytometric analysis demonstrated that the device had the capacity to activate platelets as evidenced by significant increases in circulating platelet microaggregates and activated platelets. Thrombus was observed on 20 +/- 6% of the surface area of devices implanted for up to 53 h. Adding aspirin to the antithrombotic therapy permitted two devices to remain implanted up to 96 h with reduced platelet activation and only 3% of the surface covered with thrombus. The application of heparin-based coatings significantly reduced thrombus deposition in vitro. The results suggest that with the use of appropriate antithrombotic therapies and surface coatings the Hattler Catheter might successfully provide support for acute lung failure without thrombotic complications.

Investigating the effects of random balloon pulsation on gas exchange in a respiratory assist catheter.

We are developing an intravenous respiratory assist catheter, which uses hollow-fiber membranes wrapped around a pulsating balloon that increases oxygenation and CO2 removal with increased balloon pulsation. Our current pulsation system operates with a constant rate of pulsation and delivered balloon volume. This study examined the hypothesis that random balloon pulsation would disrupt fluid entrainment within the fiber bundle and increase our overall gas exchange. We implemented two different modes for random (rates and delivered volume) versus constant pulsation. The impact on gas exchange was measured in a 3 l/min water flow loop at 37 degrees C. CO2 gas exchange for randomized beat rate mode was comparable to its corresponding average constant pulsation (e.g., constant 286 beats/min versus randomized 200-400 beats/min was 299.5+/-0.9 and 302.2+/-1.4 ml/min/m, respectively). Random volume mode CO2 exchange was also comparable to constant delivered balloon volume (100% inflation and deflation) (e.g., 294.3+/-0.6 and 301.1+/-1.7 ml/min/m, random 50-100% inflation and constant, respectively). Greater active mixing was seen with constant pulsation as compared with randomly changing the parameters of balloon pulsation.

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 non-uniform 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 plasma resistant hollow fiber membranes for artificial lungs.

Hollow fiber membranes (HFMs) used in artificial lungs (oxygenators) undergo plasma leakage (or wetting) in which blood plasma slowly fills the pores of the fiber wall, plasma leaks into gas pathways, and overall gas exchange decreases. To overcome this problem plasma resistant fibers are being developed that are skinned asymmetric or composite symmetric versions of microporous oxygenator fibers. This report evaluates several candidate plasma resistant HFMs in terms of their gas permeance and plasma resistance as measured in a surfactant wet out test. Five candidate fibers were compared with each other and with a control fiber. CO2 and O2 gas permeance (in ml/s/cm2/cm Hg) in the plasma resistant fibers ranged from 3.15E-04 to 1.71E-03 and 3.40E-04 to 1.08E-03, respectively, compared with 1.62E-02 and 1.77E-02 for the control fiber. Maximum dye bleed through for the plasma resistant fibers in the forced wet out test were significantly less than for the control fiber. CO2 gas permeance of a plasma resistant fiber imposes the greatest constraint upon artificial lung design for sufficient gas exchange. However, our results suggest sufficient plasma resistance can be achieved using special skinned and composite HFMs while maintaining an acceptable CO2 gas permeance for a broad range of artificial lung applications.

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.