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. 2022 Mar 1;144(3):031202.
doi: 10.1115/1.4053105. Epub 2022 Jan 18.

Thermal Analyses of Nanowarming-Assisted Recovery of the Heart From Cryopreservation by Vitrification

Purva Joshi  1 , Lili E Ehrlich  1 , Zhe Gao  2 , John C Bischof  2 , Yoed Rabin  3
Affiliations
Free PMC article

Thermal Analyses of Nanowarming-Assisted Recovery of the Heart From Cryopreservation by Vitrification

Purva Joshi et al. J Heat Transfer. .
Free PMC article

Abstract

This study explores thermal design aspects of nanowarming-assisted recovery of the heart from indefinite cryogenic storage, where nanowarming is the volumetric heating effect of ferromagnetic nanoparticles excited by a radio frequency electromagnet field. This study uses computational means while focusing on the human heart and the rat heart models. The underlying nanoparticle loading characteristics are adapted from a recent, proof-of-concept experimental study. While uniformly distributed nanoparticles can lead to uniform rewarming, and thereby minimize adverse effects associated with ice crystallization and thermomechanical stress, the combined effects of heart anatomy and nanoparticle loading limitations present practical challenges which this study comes to address. Results of this study demonstrate that under such combined effects, nonuniform nanoparticles warming may lead to a subcritical rewarming rate in some parts of the domain, excessive heating in others, and increased exposure potential to cryoprotective agents (CPAs) toxicity. Nonetheless, the results of this study also demonstrate that computerized planning of the cryopreservation protocol and container design can help mitigate the associated adverse effects, with examples relating to adjusting the CPA and/or nanoparticle concentration, and selecting heart container geometry, and size. In conclusion, nanowarming may provide superior conditions for organ recovery from cryogenic storage under carefully selected conditions, which comes with an elevated complexity of protocol planning and optimization.

Keywords: cryopreservation; nanowarming; simulation; thermal analysis; vitrification.

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Figures

Illustrations of (a) an MRI-based geometrical model of a human heart, (b) the FEA mesh representation of the heart, (c) a heart model contained in a cryobag, and (d) a heart model in a cylindrical container
Fig. 1
Illustrations of (a) an MRI-based geometrical model of a human heart, (b) the FEA mesh representation of the heart, (c) a heart model contained in a cryobag, and (d) a heart model in a cylindrical container
Thermal results for the benchmark case of the rat heart model—Case I (Table 3): (a) temperature distribution at the end of nanowarming superimposed on the heart model, when the lowest temperature in the heart surpasses −35 °C and (b) thermal history in the heart muscle during the process of nanowarming
Fig. 2
Thermal results for the benchmark case of the rat heart model—Case I (Table 3): (a) temperature distribution at the end of nanowarming superimposed on the heart model, when the lowest temperature in the heart surpasses −35 °C and (b) thermal history in the heart muscle during the process of nanowarming
Thermal results for the rat heart muscle contained in a cryobag in Cases I–IV (Table 3): (a) rewarming rates range when the heart muscle temperature is between the glass transition temperature and the end of nanowarming, and (b) temperature variation at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C (bars), and the maximum temperature at the instant (red diamonds)
Fig. 3
Thermal results for the rat heart muscle contained in a cryobag in Cases I–IV (Table 3): (a) rewarming rates range when the heart muscle temperature is between the glass transition temperature and the end of nanowarming, and (b) temperature variation at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C (bars), and the maximum temperature at the instant (red diamonds)
Temperature distribution superimposed on the rat model at the end of nanowarming in Case IV (Table 3) when the lowest temperature surpasses −35 °C
Fig. 4
Temperature distribution superimposed on the rat model at the end of nanowarming in Case IV (Table 3) when the lowest temperature surpasses −35 °C
Thermal results for the rat heart muscle contained in a cryobag for Cases III- VI: (a) rewarming rates range when the heart muscle temperature is between the glass transition temperature and the end of nanowarming, (b) temperature variation at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C (bars), and the maximum temperature at the instant (red diamonds), and (c) temperature distribution superimposed on the heart model at the end of nanowarming for Case VI
Fig. 5
Thermal results for the rat heart muscle contained in a cryobag for Cases III- VI: (a) rewarming rates range when the heart muscle temperature is between the glass transition temperature and the end of nanowarming, (b) temperature variation at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C (bars), and the maximum temperature at the instant (red diamonds), and (c) temperature distribution superimposed on the heart model at the end of nanowarming for Case VI
Thermal results for the rat heart muscle contained in a cryobag, small cylindrical container, and a large cylindrical container in Case II (Tables 1 and 3): (a) rewarming rates range when the heart muscle temperature is between the glass transition temperature and the end of nanowarming and (b) temperature variation at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C (bars), and the maximum temperature at the instant (red diamonds)
Fig. 6
Thermal results for the rat heart muscle contained in a cryobag, small cylindrical container, and a large cylindrical container in Case II (Tables 1 and 3): (a) rewarming rates range when the heart muscle temperature is between the glass transition temperature and the end of nanowarming and (b) temperature variation at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C (bars), and the maximum temperature at the instant (red diamonds)
Temperature distribution comparison for rat heart model between a small cylindrical container and a large cylindrical container in Case II (Tables 1 and 3, Fig. 6): (a) and (b) temperature distribution in the heart cross sections where the lowest temperature is found; (c) and (d) the corresponding temperature distribution across the heart and the surrounding CPA solution; and (e) and (f) the FEA mesh in that cross section, highlighting the heart geometric model, where red represents the heart muscle, blue represents the surrounding CPA solution, and pink represents the CPA solution within the heart chambers. Note that the same rat heart model is used in both cases, but the smaller cylinder is selected to tightly fit the heart, while the geometric center of the heart is aligned with the cylinder centerline for the larger container. This difference in positioning results in different heart cross section contours displayed between Figs. 7(e) and 7(f).
Fig. 7
Temperature distribution comparison for rat heart model between a small cylindrical container and a large cylindrical container in Case II (Tables 1 and 3, Fig. 6): (a) and (b) temperature distribution in the heart cross sections where the lowest temperature is found; (c) and (d) the corresponding temperature distribution across the heart and the surrounding CPA solution; and (e) and (f) the FEA mesh in that cross section, highlighting the heart geometric model, where red represents the heart muscle, blue represents the surrounding CPA solution, and pink represents the CPA solution within the heart chambers. Note that the same rat heart model is used in both cases, but the smaller cylinder is selected to tightly fit the heart, while the geometric center of the heart is aligned with the cylinder centerline for the larger container. This difference in positioning results in different heart cross section contours displayed between Figs. 7(e) and 7(f).
An example of temperature distribution in the human heart model when rewarmed with nanoparticles while following a thermal protocol design for the rat heart model (Case II)
Fig. 8
An example of temperature distribution in the human heart model when rewarmed with nanoparticles while following a thermal protocol design for the rat heart model (Case II)
Thermal results for the human heart muscle contained in a cryobag for a modified thermal protocol while assuming properties of VS55 + 0.6 M sucrose: (a) temperature distribution at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C and (b) during the process of nanowarming
Fig. 9
Thermal results for the human heart muscle contained in a cryobag for a modified thermal protocol while assuming properties of VS55 + 0.6 M sucrose: (a) temperature distribution at the end of nanowarming when the lowest temperature in the heart surpasses −35 °C and (b) during the process of nanowarming
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