J Cardiovasc Transl Res. 2014 Dec;7(9):781-7.

Impact of balloon inflation pressure on cell viability with single and multi lumen catheters.

Dib N, Schwalbach DB, Plourde BD, Kohler RE, Dana D, Abraham JP.

Translational Research Institute Inc, Gilbert, AZ, 85297, USA.

 

Abstract

Infusion catheters, when used in combination with balloons, are subjected to pressure created by inflation of the balloon. The compression can reduce the catheter flow area and cause elevated shear stresses in the fluid. A model and experiments were developed with a range of applied balloon pressures to investigate whether such situations may cause cell lysis during stem-cell infusion through single-lumen catheters. It was found that for balloon inflation pressures in excess of ~7 atm, it is possible for cell injury to occur, although the critical pressure depends on the fluid viscosity. The study was then applied to a multi-lumen catheter which was designed to resist compression. That device was able to handle very elevated balloon pressures and flow rates before cell lysis became a concern.

PMID: 25413890

 

Supplements:

Design and Development of a New Cell Infusion Catheter

Plourde BD, Abraham JP*

University of St. Thomas, School of Engineering, 2115 Summit Ave, St. Paul, MN 55105-1079

*Corresponding author: jpabraham@stthomas.edu

 

Abstract

A new catheter (ND Infusion Catheter) has been designed to be able to infuse stem cells or other medications into the cardiovascular system for treatment of cardiovascular and peripheral vascular diseases. The catheter is constructed with multiple small tubes which spray the cell suspension or medication in a diffuse pattern across the vessel. The diffuse spray improves dispersion and mixing compared to conventional single-lumen catheters. The catheter design makes is more resistance to compression by the inflation balloon and consequently, better preserves living stem cells which would otherwise be damaged. The catheter is inserted with a guidewire and contains an inflatable balloon which enables it to be used with various vessel sizes. Numerical simulations have been performed on the fluid dynamics within and downstream of the catheter. Patient trials of the device are ongoing.

 

Introduction

Delivery of stem cells or other medications is a crucial step in many medical therapies. For stem cells in particular, the viable cells must be delivered to the targeted region where they are able to regenerate tissues following infarction, heart failure, or other conditions. During the infusion process, a pressurized balloon is inflated which occludes the vessel upstream of the infusion site and stops blood flow during the therapy procedure.

A traditional catheter has a single lumen which is available for the passage of medication/stem cells. While standard in practice, the traditional lumen has two features which limit its ability to function in these procedures. First, the lumen can be compressed following the inflation of the balloon so that the open space is reduced. This reduction leads to a high stress within the fluid during the injection. Secondly, the single lumen limits the downstream mixing of the liquid and allows clumps of cells to exit the catheter and potentially cause embolization and myocardial infarction. These two features motivated the design, development, and testing of a novel multi-lumen catheter for the injection of steam cells within arteries. The multi-lumen catheter is shown in Figure 1.

 JA fig1

Figure 1 – The multi-lumen catheter with descriptive annotations

 

To visually distinguish the effect of the multi-lumen device from that of a standard single-lumen catheter, Figure 2 has been prepared. The left-hand part of the figure shows the multi-lumen device, introduced over a guidewire and cells emerging from the individual holes. The right-hand image shows cells emerging together from a single exit port.

JA fig2

Figure 2 – Comparison images of the multi-lumen and single-lumen devices.

 

A following image (Figure 3) shows a sectioned view of the multi-lumen catheter positioned within an artery passage. A more detailed description of some of the internal components of the device is provided in (1).

 JA fig3

Figure 3 – Sectioned view of multi-lumen catheter within an artery

 

The following sections will describe analysis performed on the mixing capacity of the multi-lumen catheter compared to that of a standard single-lumen variant. Additionally, results from experiments and simulations are shown to address the influence of the catheter on the viability of stem cells leaving the exit ports.

 

Analysis

In (1) and (2) a description of the numerical simulations is presented and is not reshown here for brevity. The comparison between the single- and multi-lumen catheters accounted for many different operating conditions such as the presence or absence of the inflating balloon, low and high stem cell/medication flowrates, and low and high values of viscosity. The simulations enabled a Design of Simulation study to be performed (similar to a Design of Experiments study) as discussed in (3). It was found that the multi-lumen catheter was more able to disperse the injectant across the artery cross section under certain common operating conditions. An image of an emerging and spreading bolus of injectant is displayed in Figure 4. The figure provides some qualitative description of how the spreading occurs but for design, it is essential to quantify the portions of the cross section occupied by a concentration levels that are sufficiently high to be therapeutic; for instance, 1% or 10% concentration levels. It is also important to compare the concentration distributions for the various cases discussed earlier.

 JA fig4

Figure 4 – Bolus of cells/medication spreading as they move downstream

 

In (1), it was shown that there was little impact of fluid viscosity and the presence/absence of the inflation balloon. The multi-lumen catheter exhibited improved hydraulic performance (lower flow resistance) compared to the single-lumen device. Finally, in some cases, such as with an inflation balloon, the multi-lumen device improved dispersion.

Next, the impact of the catheter design on cell health was studied. This part of the study contained two steps. First, numerical simulations were performed to quantify the shear stress within the fluid and those stresses were compared against hemolysis thresholds for red blood cells. Next experiments were performed on living cells which were injected through both catheters (single- and multi-lumen). These results were previously discussed in (4) and partially in (5-7).

From the simulations, it was found that for a single-lumen catheter, progressive increases in the inflation balloon pressure reduced the lumen cross section. This reduction in cross section caused an increase in the shear stress as the fluid was infused through the device. When the balloon inflation pressure reached values of approximately -8 atm, shear stress levels were high enough to cause injury to the cells. These findings were made for both a low and a high viscosity carrying-fluid for the stem cells.

A similar study was made of the multi-lumen device. It was shown that the construction of the device made it much more resistant to compression so that for any reasonable value of balloon inflation pressure (up to 12 atm), there was no concern of cellular injury.

The corresponding loss of cell viability from experiments showed that for pressures in excess of approximately 6 atm, there was a significant portion of cell injury for a single-lumen device however no such cell injury was seen for the multi-lumen device.

Finally, for the multi-lumen device, the injected flowrate was systematically increases and the shear stress within the fluid calculated. Flowrates up to 10 ml/min and two different carrying-fluid viscosities were used. It was found that even at these very high injection rates, the shear stress experienced by cells traveling through the multi-lumen device would be sufficiently low so cell injury would not occur.

 

Concluding Remarks

This report summarizes a multi-year investigation on the viability of multi-lumen catheters to serve as infusion devices for treating cardiovascular disease. The investigation has had many foci. First, a study was performed to compare the diffusion capacity of the catheter with that of a single-lumen device. It was found that the multi-lumen device exhibited a reduction flow resistance (a lower applied pressure is required to cause a prescribed flow). Secondly, a sensitivity study was carried out to quantify the impact of various operating parameters (flow rate, viscosity, presence or absence of balloon, etc.) on the diffusion. It was found that viscosity and balloon presence has a small effect.

An independent study was carried out to assess the shear stress exerted on the fluid flowing through the catheter with special attention given to the impact that the inflation balloon had on the stress. For a single-lumen catheter, progressive increases in the balloon pressure caused a reduction in the lumen open area so that the fluid was forced to pass through a smaller space. This reduction in channel size led to an increase in the shear stress on the fluid and consequently, concern that cells could be injured by mechanical hemolysis. Calculations show that for balloon inflation pressures in excess of approximately 7-8 atm, mechanical injury was a concern. Similar calculations for the multi-lumen device showed that not only was it resistant to compression from the balloon, but also the fluid rate through the catheter could be increased markedly (up to 10 ml/min) before cell injury became a concern.

The calculations were then compared with benchtop experiments which are described in detail in the referenced literature. Those experiments confirmed the calculations that the single-lumen device presents a much greater hazard to stem cells than does the multi-lumen device. In fact, according to the experiments, when the inflation balloon pressure rises to approximately 6 atm, a decrease in cell viability is observed.

These mutually supporting studies confirm the operation of the multi-lumen device for the injection of stem cells for the treatment of cardiovascular or other diseases.

 

Acknowledgements:

The research reported on here was supported by Translational Research Institute. The current manuscript was prepared without financial support. The authors have no financial connection with the company.

 

References

  1. Schwalbach DB, Plourde BD, Abraham JP, Kohler RE, 2013 Drug dispersion for single- and multi-lumen catheters, Journal of Biomedical Science and Engineering 6:1021-1028.
  1. Plourde BD, Schwalbach DB, Abraham JP, Kohler RE, 2014 intracoronary injection of medication from multi-lumen injection catheters, Journal of Medical Devices 8:020901.
  2. Sparrow EM, Abraham JP, Chevalier PW , 2005 A DOS-enhanced numerical simulation of heat transfer and fluid flow through an array of offset fins with conjugate heating in the bounding solid, Journal of Heat Transfer 127: 27-33.
  3. Dib N, Schwalbach DB, Plourde BD, Kohler RE, Dana D, Abraham JP, 2014 Single lumen balloon angioplasty catheter reduces cell viability when compared to multi lumen infusion catheter, Cardiovascular Translation Research 7:781-787.
  4. Dib N, Kohler RE, Abraham JP, Plourde BD, Schwalbach DB, Dana D, Baird BJ, Flower TR, Myers L, Hunkler K, 2013 TCT-811 Stem cell viability significantly reduced after passing through a standard single lumen over-the-wire 0.014 balloon angioplasty catheter, Journal of the American College of Cardiology 62:B246.
  5. Dib N, Kohler RE, Abraham JP, Plourde BD, Schwalbach DB, Dana D, Baird BJ, Flower TR, 2013 Stem cell viability significantly reduced after passing through a standard single lumen over-the-wire 0.014 inch balloon angioplasty catheter, Journal of the American College of Cardiology, 62:B246.
  6. Dib N, Abraham JP, Plourde BD, Schwalbach DB, Dana D, Myers L, Hunkler K, D’Silva SR, Flower TR, Kohler RE, 2014 TCT-155 a novel multi lumen compliant balloon catheter (ND infusion catheter) preserves stem cell viability and improves dispersion when compared to a standard single lumen balloon angioplasty catheter, Journal American College of Cardiology 64:11.

 

 

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