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

https://doi.org/10.1016/j.medengphy.2016.05.007Get rights and content

Highlights

  • Two catheter cooling approaches show 200 W of cooling.

  • Four variables were studied including infusion flow rate.

Abstract

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.

Introduction

Heart attack and stroke continue to be leading causes of death and serious disability in the United States [1]. Removing vessel blockages through mechanical intervention or drug therapy is a common treatment. This treatment reveals a paradox. Blockage removal and subsequent blood flow restoration to previously oxygen-starved tissue, while necessary for survival, is also associated with negative health effects. Reducing these negative effects, referred to as reperfusion injury, is the focus of our research. Reperfusion injury can be significant, perhaps as much as 50% of the final tissue injury [2].

Hypothermia is a promising strategy for reducing reperfusion injury [3]. To harness the protective power of hypothermia five difficult questions emerge: (1) when to initiate cooling, (2) how quickly to cool, (3) what is the target temperature to cool, (4) how long should cooling be sustained, and (5) how quickly should you rewarm. Research indicates that rapid cooling, as close to the ischemic event as possible, is preferred. Research also suggests that quicker cooling provides greater protection with tissue target temperatures around 33 °C [4]. Cooling blankets and other external whole-body cooling techniques typically take 1–2 h to reach mild hypothermia (33 °C) [5].

In contrast to whole-body cooling, localized hypothermia provides faster cooling, focusing its cooling effect in the area-at-risk region alone rather than the entire body. One method to cool locally is to infuse cold saline or blood directly into the targeted area via a guide catheter. Delivering and mixing cooled fluid into an arterial bloodstream reduces mixed blood temperature and the temperature of the tissue being perfused. In one animal study, a cooling catheter delivered cooled blood at temperatures between 27 and 29 °C at 30 ml/min to at-risk heart tissue. This method reduced tissue temperature by 3 °C in five minutes using 30 W of cooling [6]. Typical whole-body coolers apply approximately 200–300 W of cooling [7], [8] and typically achieve much slower 1–2 °C/h cooling rates [5].

Focusing on stroke, localized hypothermia models have been developed to predict tissue temperature drop inside the brain [9], [10]. Slotboom et al. created a thermal model of three different micro-catheter configurations in which the distal tip passes through a completely occluding blockage in the middle cerebral artery (MCA). Using a simplified version of Pennes bioheat equation and a fixed infusion temperature of 15 °C for all infusion rates, brain tissue temperature was predicted as a function of time. Assuming 300 g of ischemic brain tissue, predicted cooling rates were approximately 1 °C/min at 30 ml/min infusion rate with systemic temperature drops of less than 1 °C in an hour. Konstas et al. developed a discrete thermal model of brain tissue in 3D to determine the feasibility of intracarotid cold saline infusion (ICSI), exploring minimum possible tissue temperatures, rate of tissue cooling, and impact of hemodilution. Similar to Slotboom et al., Konstas et al. used a smaller catheter inside a larger catheter to insulate the saline infusion process. In contrast to Slotboom et al., Konstas et al. placed the catheter distal tip in the internal carotid artery (ICA) instead of an occluded MCA. Assuming a flow rate of 30 ml/min and an infusion temperature of about 3 °C, mild-moderate hypothermia (33–34 °C) was possible in 10 min.

Both these studies assumed a batch cooling system, Fig. 1. Looking at Fig. 1, “Tent” is the catheter entering fluid temperature, “Tdel” is the delivered fluid temperature at the target area, prior to mixing with the natural blood flow. “F” and “P” denote the flowrate and pressure. Alternatively, a closed-loop cooling system uses continuous cooling of autologous blood with an external heat exchanger (Fig. 3).

While these previous thermal models showed the feasibility and potential of localized brain tissue cooling in the MCA and ICA, a thorough examination of practical clinical parameters is needed. We explored the cooling performance impact of four clinical parameters: catheter configuration or selection, catheter placement inside the body, cooling system approach, and infusion flow rate. An in-depth heat transfer analysis reveals opportunities to optimize both the design and the operation of localized organ cooling devices to reduce reperfusion injury. While saline batch cooling systems provide superior cooling capacity and lower delivered infusion temperatures, the difficulty of catheter design, localized hemodilution, and high pumping pressures remains.

Section snippets

Materials and methods

To explore catheter tissue cooling potential we (1) developed an in vitro mock circulatory loop that mimics the thermal fluid environments inside the internal carotid artery, (2) developed a continuous closed-loop cooling system, (3) developed mathematical models that were validated with experiments using the mock loop, and (4) exercised validated models that predicted infusion delivery temperatures for commercially available catheter designs and configurations.

Model validation for a continuous closed-loop cooling system

The mathematical model was compared with mock circulatory system measurements. Fig. 7 shows the Configuration I (Table 1) delivered temperature results data compared to the model. The eccentric model, which assumes the catheter lies against the inner wall of the glass aorta and carotid artery, predicted the temperatures within 2 °C for all flow rates tested. The concentric model, which assumes the catheter is centered along the axis of the glass aorta and carotid artery, predicted the

Discussion

At the 9th World Stroke Conference in October 2014 results of a major trial (MR CLEAN, n = 500 patients) evaluating intracranial mechanical thrombectomy were presented showing superior outcomes compared to standard medical therapy using chemical thrombectomy, including a 38% reduction in infarct size [19]. The newest generation of mechanical devices called stentrievers was used in 97% of the cases. Two similar trials (ESCAPE and EXTEND IA) were stopped early because of benefits in the

Conclusion

In conclusion, this work explored practical clinical parameters that control the effectiveness of localized hypothermia for stroke. Model results showed that delivery temperatures (Tdel) ranged from 7 to 25 °C and the maximum cooling capacity to tissue was 210 W at 100 ml/min. The work described here can be used to select, design and operate medical devices that create localized tissue cooling, potentially reducing reperfusion injury occurring in ischemic strokes, heart attacks, and organ

Conflicts of interest

All of the authors (TLM, DRM, and JEM) work for FocalCool, LLC a company developing cooling catheters for localized hypothermia. Funding for our work comes from Federal and State funding agencies.

Funding

Funding for this work has come from Federal and State agencies.

Ethical approval

This study does not involve animal or human subjects. No ethical approval required.

Acknowledgments

We acknowledge the support of NIH's National Heart, Blood, and Lung Institute (NHLBI) through Grant number R44HL088789. The content is solely the responsibility of the authors and does not necessarily represent the official view of NHLBI or NIH. The support of the South Jersey Technology Park and Rowan University is gratefully acknowledged.

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