Thomas L. Merrill

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.

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.

Development of a Novel Automated Ion Channel Recording Method Using “Inside-Out” Whole-Cell Membranes

Efforts to develop novelmethods for recording from ion channels have been receiving increased attention in recent years. In this study, the authors report a unique “inside-out” whole-cell configuration of patch-clamp recording that has been developed. This method entails adding cells into a standard patch pipette and, with positive pressure, obtaining a gigaseal recording from a cell at the inside tip of the electrode. In this configuration, the cellmay be moved through the air, first rupturing part of the cellularmembrane and enabling bath access to the intracellular side of the membrane, and then into a series of wells containing differing solutions, enabling robotic control of all the steps in an experiment. The robotic system developed here fully automates the electrophysiological experiments, including gigaseal formation, obtaining whole-cell configuration, data acquisition, and drug application. Proof-of-principle experiments consisting of application of intracellularly acting potassium channel blockers to K+ channel cell lines resulted in a very rapid block, aswell as block reversal, of the current. This technique allows compound application directly to the intracellular side of ion channels and enables the dissociation of compound inactivities due to cellular barrier limitations. This technique should allow for parallel implementation of recording pipettes and the future development of larger array-based screening methods.

Thermally controlled bubble collapse in binary solutions

Abstract This paper theoretically analyzes thermally controlled bubble collapse in binary solutions. Using a finite difference approach with an adaptive grid, three aspects of bubble collapse are investigated: counter-diffusion, initial bubble diameter, and absorber cooling rate. Results illustrate how counter-diffusion of the absorbent, acting to preserve the bubble life span, is offset by convective mass transfer arising from bubble interface motion. Predicted bubble mass transfer rates for an ammonia water system increase with the square of the bubble radius (diameters: 1.8–5.6 mm) and with increased absorber cooling rates. Model predictions compare well with simple semi-empirical correlations for bubble heat and mass transfer coefficients.

Design of a Cooling Guide Catheter for Rapid Heart Cooling

Cardiovascular disease is the leading cause of death in the United States. Despite decades of care path improvements approximately 30% of heart attack victims die within 1 year after their first heart attack. Animal testing has shown that mild hypothermia, reducing tissue temperatures by 2-4°C, has the potential to save heart tissue that is not adequately perfused with blood. This paper describes the design of a cooling guide catheter that can provide rapid, local cooling to heart tissue during emergency angioplasty. Using standard materials and dimensions found in typical angioplasty guide catheters, a closed-loop cooling guide catheter was developed. Thermal fluid modeling guided the interior geometric design. After careful fabrication and leak testing, a mock circulatory system was used to measure catheter cooling capacity. At blood analog flow rates ranging from 20 ml/min to 70 ml/min, the corresponding cooling capacity varied almost linearly from 20 W to 45 W. Animal testing showed 18 W of cooling delivered by the catheter can reduce heart tissue temperatures rapidly, approximately 3° in 5 min in some locations. Future animal testing work is needed to investigate if this cooling effect can save heart tissue.

Heat transfer analysis of catheters used for localized tissue cooling to attenuate reperfusion injury

Recent revascularization success for ischemic stroke patients using stentrievers has created a new opportunity for therapeutic hypothermia. By using short term localized tissue cooling interventional catheters can be used to reduce reperfusion injury and improve neurological outcomes. Using experimental testing and a well-established heat exchanger design approach, the ɛ-NTU method, this paper examines the cooling performance of commercially available catheters as function of four practical parameters: (1) infusion flow rate, (2) catheter location in the body, (3) catheter configuration and design, and (4) cooling approach. While saline batch cooling outperformed closed-loop autologous blood cooling at all equivalent flow rates in terms of lower delivered temperatures and cooling capacity, hemodilution, systemic and local, remains a concern. For clinicians and engineers this paper provides insights for the selection, design, and operation of commercially available catheters used for localized tissue cooling.

A hemolysis study of an intravascular blood cooling system for localized organ tissue cooling

Therapeutic hypothermia can reduce both ischemic and reperfusion injury arising after strokes and heart attacks. New localized organ cooling systems offer a way to reduce tissue damage more effectively with fewer side effects. To assess initial blood safety of our new organ cooling system, the CoolGuide Cooling System (CCS), we investigated safe operating conditions and configurations from a hemolysis perspective. The CCS consists of a peristaltic pump, a custom-built external heat exchanger, a chiller, biocompatible polyvinyl cellulose (PVC) tubing, and a control console. The CCS cools and circulates autologous blood externally and re-delivers cooled blood to the patient through a conventional catheter inserted directly into the organ at risk. Catheter configurations used included: a 7F guide catheter only, a 7F guide with a 0.038” wire inserted through the center and advanced 2 cm distal to the catheter distal tip, a 6F guide catheter only and a 6F guide with a 0.014” guidewire similarly inserted through the center. Using porcine blood, an in vitro test rig was used to measure the degree of hemolysis generation, defined as the percentage change in free hemoglobin, adjusted for total hemoglobin and hematocrit, between exiting and entering blood. The highest degree of hemolysis generation was 0.11±0.04%, based on the average behavior with a 6F catheter and a 0.014” guidewire configuration at a blood flow rate of approximately 130 mL/min. In terms of average percentage free hemoglobin exiting the system, based on total hemoglobin, the highest value measured was 0.17%±0.03%, using this 6F and 0.014” guidewire configuration. This result is significantly below the most stringent European guideline of 0.8% used for blood storage and transfusion. This study provides initial evidence showing hemolysis generation arising from the CoolGuide Cooling System is likely to be clinically insignificant.

Computational Modeling of the Canine Middle Cerebral Artery During Localized Hypothermia Stroke Treatment

Stroke is caused by an interruption of brain blood supply and is one of the leading causes of death and disability in the United States. Each year 795,000 people experience a new stroke, of which 87% are ischemic [1]. The primary goal in stroke treatment is restoring blood flow in the effected regions of the brain, typically by using mechanical thrombectomy devices. However, after blood flow is restored, additional damage can occur in the form of reperfusion injury. Studies have shown that up to 50% of cell death from an ischemic event occurs as a result of reperfusion injury in cardiac patients [2].© 2013 ASME

Localized Brain Tissue Cooling for Use During Intracranial Thrombectomy

The primary goal of current ischemic stroke treatment is quickly restoring blood perfusion. Recanalization is linked to improved neurological outcomes [1]. Resulting tissue necrosis, however, following a stroke has two causes: 1) ischemic injury and 2) reperfusion injury. Therefore, development of neuroprotective agents specifically beneficial against reperfusion injury are required.Copyright

Ex Vivo Blood Damage Measurement for an Intravascular Blood Cooling and Delivery System

An intravascular cooling system was developed to provide localized cooling directly to organs. Therapeutic hypothermia has been shown to reduce both ischemic and reperfusion injury related damage in both animal models and clinically for a range of organs including the heart, brain, and kidneys [1–4]. Cooling may ultimately aid in reducing damage from heart attack and stroke as well as problems associated with other organs.Copyright