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.

Development of a low flow resistance intravenous oxygenator.

A potentially attractive support device for patients with acute respiratory failure is an intravenous membrane oxygenator. One problem, however, is that the membrane surface area required for sufficient gas exchange can unduly increase vena caval pressure drop and impede venous return. The purpose of this study was to design and develop an intravenous oxygenator that would offer minimal venous flow resistance in situ. The device uses a constrained fiber bundle of smaller cross sectional size than the vena cava so as to effect an intentional shunt flow of venous blood around the fiber bundle and reduce the venous pressure drop caused by the device. A pulsating balloon within the fiber bundle redirects part of this shunt flow into reciprocating flow in and out of the fiber bundle. This offers dual advantages: 1) Blood flow through the fiber bundle is mainly perpendicular to the fibers; and 2) the requisite energy for driving flow comes largely from the pneumatic system pulsating the balloon, not from a venous pressure drop. In this mode a full length device with a 2 cm fiber bundle in a 2.5 cm blood vessel would offer a pressure drop of only a few millimeters of mercury. The use of constrained fiber bundles requires good uniformity of fiber spacing for effective gas exchange. Several prototypes have been fabricated, and CO2 and O2 exchange rates of up to 402 and 347 ml/min/m2 have been achieved during acute animal implantation.

Recent progress in engineering the Pittsburgh intravenous membrane oxygenator.

The University of Pittsburgh intravenous membrane oxygenator (IMO) is undergoing additional engineering development and characterization. The focus of these efforts is an IMO device that can supply as much as one-half basal O2 consumption and CO2 elimination rates while residing within the inferior and superior vena cavae after peripheral venous insertion. The current IMO design consists of a bundle of hollow fiber membranes potted to manifolds at each end, with an intra-aortic type balloon integrally situated within the fiber bundle. Pulsation of the balloon using helium gas and a balloon pump console promotes fluid and fiber motion and enhances gas exchange. During the past year, more than 15 IMO prototypes have been fabricated and extensively bench tested to characterize O2 gas exchange capacity, balloon inflation/deflation over relevant frequency ranges, and the pneumatics of the sweep gas pathway through the device. The testing has led to several engineering changes, including redesign of the helium and sweep gas pathways within the IMO device. As a result, the maximum rate of balloon pulsation has increased substantially above the previous 70 bpm to 160 bpm, and the vacuum pressure required for sufficient sweep gas flow has been reduced. The recent IMO prototypes have demonstrated an O2 exchange capacity of as much as 90 ml/min/m2 in water, which appears within 70% of our design goal when extrapolated to scaled up devices in blood.

A novel method for measuring hollow fiber membrane permeability in a gas-liquid system.

Designing an effective intravenous membrane oxygenator requires selecting hollow fiber membranes (HFMs) that present minimal resistance to gas exchange over extended periods of time. Microporous fiber membranes, as used in extracorporeal oxygenators, offer a minimal exchange resistance, but one that diminishes with time because of fiber wetting and subsequent serum leakage. Potentially attractive alternatives are composite HFMs, which inhibit fiber wetting and serum leakage by incorporating a true membrane layer within their porous walls. To evaluate composite and other HFMs, the authors developed a simple apparatus and method for measuring HFM permeability in a gas-liquid system under conditions relevant to intravenous oxygenation. The system requires only a small volume of liquid that is mixed with a pitched blade impeller driven by a direct current motor at controlled rates. Mass flux is measured from the gas flow exiting the fibers, eliminating the necessity of measuring any liquid side conditions. The authors measured the CO2 exchange permeabilities of Mitsubishi MHF 200L composite HFMs, KPF 280E microporous HFMs, and KPF 190 microporous HFMs. The membrane permeabilities to CO2 were 9.3 x 10(-5) ml/cm2/sec/cmHg for the MHF 200L fiber, 4.7 x 10(-4) ml/cm2/sec/cmHg for the KPF 280E fiber, and 2.8 x 10(-4) ml/cm2/sec/cmHg for the KPF 190 fiber. From these results it is concluded that 1) because of liquid-fiber surface interactions, the permeabilities of the microporous fibers are several orders of magnitude less than would be measured for completely gas filled pores, emphasizing the importance of measuring microporous fiber permeability in a gas-liquid system; and 2) the liquid diffusional boundary layer adjacent to the fibers generated by the pitched blade impeller is unique to each fiber, resulting in different boundary layer characterizations.

Acute in vivo studies of the Pittsburgh intravenous membrane oxygenator.

The efficacy of an innovative intravenous membrane oxygenator (IMO) was tested acutely (6-8 hrs) in seven calves. The IMO prototypes consisted of a central polyurethane balloon within a bundle of hollow fibers with a membrane surface area of 0.14 m2. The IMO devices were inserted through the external jugular vein into the inferior vena cava of anesthetized calves (68.9 +/- 2.3 kg). Rhythmic balloon pulsation (60-120 bpm) was controlled with an intra-aortic balloon pump console. Oxygen sweep gas was delivered through the device at 3.0 L/min. Gas concentrations were monitored continuously by mass spectroscopy. The principal results were as follows: 1) oxygen and carbon dioxide exchange ranged from 125 to 150 ml/min/m2 and 150 to 200 ml/min/m2, respectively; 2) there was at least a 30-50% augmentation of gas exchange with balloon pulsation; 3) maximum exchange occurred with 60-90 bpm balloon pulsations; and 4) hemodynamic parameters remained unchanged. There were no device related complications, and the feasibility of insertion of the device by a cervical cut-down was established. These acute in vivo experiments show that the Pittsburgh IMO device can exchange oxygen and carbon dioxide gases in vivo at levels consistent with this current prototype design, and that intravenous balloon pulsation significantly enhances gas exchange without causing any end-organ damage.

Development of an intravenous membrane oxygenator: enhanced intravenous gas exchange through convective mixing of blood around hollow fiber membranes.

In vitro testing of a new prototype intravenous membrane oxygenator (IMO) is reported. The new IMO design consists of matted hollow fiber membranes arranged around a centrally positioned tripartite balloon. Short gas flow paths and consistent, reproducible fiber geometry after insertion of the device result in an augmented oxygen flux of up to 800% with balloon activation compared with the static mode (balloon off). Operation of the new IMO device with the balloon on versus the balloon off results in a 400% increase in carbon dioxide flux. Gas flow rates of up to 9.5 L/min through the 14-cm-long hollow fibers have been achieved with vacuum pressures of 250 mm Hg. Gas exchange efficiency for intravenous membrane oxygenators can be increased by emphasizing the following design features: short gas flow paths, consistent and reproducible fiber geometry, and most importantly, an active means of enhancing convective mixing of blood around the hollow fiber membranes.

Vibration analysis of vessel wall motion with intra vena caval balloon pumping.

The intravenous membrane oxygenator (IMO) incorporates a centrally positioned balloon surrounded by hollow microporous fibers. Previous studies using this configuration have demonstrated that rhythmic pulsation of the balloon enhances gas exchange, presumably by three dimensional convective mixing. This study sought to characterize vessel wall vibrations imparted by intra vena caval balloon pumping. An in vitro flow loop incorporating a current IMO prototype was used for these measurements. The IMO prototype was inserted in a modeled vena cava on which ultrasonic dimension transducers were mounted on the outer surface. The flow loop was operated at physiologic flow rates. The balloon was activated, and dynamic vessel diameter measurements were recorded as the pumping frequency was varied from 40 to 120 beats per minute (bpm). A Fast Fourier Transform algorithm generated a frequency spectrum at each bpm and for two different balloon configurations; a single balloon versus a tripartite arrangement, the authors' results demonstrate that the mean amplitude of vena caval oscillations varied with bpm, and that this variation followed the trends in oxygen transfer rates. This suggests that the motion of the vessel wall may contribute to convective mixing of blood. In addition, this work demonstrated significant differences in the frequency spectra associated with our two balloon configurations.

Current progress in the development of an intravenous membrane oxygenator.

In vitro testing of an intravenous membrane oxygenator (IMO) consisting of hollow fiber membranes arranged around a centrally positioned balloon is reported. A total of six IMO prototypes were mounted in a specially designed mock circulatory loop and perfused with physiologic saline or fresh abattoir ox blood to investigate their oxygen and carbon dioxide transfer capabilities. One IMO prototype was mounted in the flow loop and perfused with saline for 13 continuous days to test the durability and reliability of the prototype design. It is the authors' hypothesis that the rhythmic inflation and deflation of the balloon increases convective mixing and cross-flow of blood around the fibers, thereby enhancing gas exchange capabilities. The results of these trials support this contention, namely that gas exchange efficiency rose with increasing frequency of balloon pulsation. No significant deterioration in oxygen transfer was observed in the durability test prototype, which was continuously perfused with saline for 13 days.

Optimal management of a ventricular assist system. Contribution of flow visualization studies.

The Novacor (Baxter Novacor, Oakland, CA) Left Ventricular Assist System (LVAS) incorporates a versatile microprocessor based controller that permits a variety of operating modes. These include internally triggered automatic synchronous counterpulsation, electrocardiogram triggered synchronous operation, and full to empty or fixed rate asynchronous operation. The aim of this pilot study was to determine the extent to which washing of the blood contacting surfaces of the pump may be optimized by suitable choice of operating mode. Visualization of flow fields adjacent to surfaces in confined areas requires small, neutrally buoyant tracer particles for feature extraction. A novel technique using fluorescent tracer particles (100 microns), an argon laser, and a low pass optical filter has been developed for this purpose. Particle motion was tracked from video images and calculations were made of velocity. Flow visualization was performed under conditions that simulated clinically observed hemodynamic conditions, typical of the immediate post-implant period. At a given LVAS output, fluid speed in the vicinity of the inflow valve tended to increase at higher LVAS beat rates (and consequently lower LVAS stroke volumes). This and future work may well be useful in selecting the optimum modes of LVAS operation as a function of the hemodynamic status of the patient.

Respiratory dialysis. A new concept in pulmonary support.

Use of a new intravenous oxygenator made of hollow fiber membranes arranged around a centrally positioned balloon is reported. In vitro studies using fluorescent image tracking velocimetry and gas exchange analysis demonstrated enhanced convective mixing with balloon pulsations and augmented gas flux (100% increase in pO2) compared with the device in its static configuration. In vivo observations confirmed a greater than 50% increase in O2 flux with balloon activation. Those parameters that produce radial flow and convective mixing in vitro enhance gas flux in vivo, thus confirming the efforts to exceed the fluid limit translate into improved gas exchange.