Ann Thorac Surg 2006;82:1088-1089
© 2006 The Society of Thoracic Surgeons
New technology
Invited commentary
Charles Hoopes, MD
Surgery/Transplantation, University of California San Francisco, 350 Parnassus Ave, Suite 150, San Francisco, CA 94143
(Email: hoopesc{at}surgery.ucsf.edu).
Physical stress kills cells at low temperatures. Nonetheless, "cooling" has a long history in both cardiac surgery and transplantation as a mechanism for tissue preservation in the context of lowered metabolic demand. However, there are limits to low temperature preservation. In general, freezing of living tissues results in intracellular ice formation and osmotic contraction (ie, thawing or reperfusion results in osmotic reexpansion with cell lysis and death). Vertebrate species in winter subzero temperatures have solved this physiological conundrum by the accumulation of permeable osmolytes, or cryoprotectants, which depress the equilibrium freezing point and reduce cell dehydration, thereby limiting osmotic contraction and mechanical injury to cell membranes. Abe and colleagues [1] present a novel, albeit poorly understood, method of supercooling with potential application to pulmonary allograft preservation. Given the increasing interest in normothermic perfusion, the host of antiaptotic/antioxidant inhibitors of cytokine induced reperfusion injury, and the well-documented injury profile of tissue at low temperatures, is there a role for new hypothermic technologies in organ preservation? The simple answer is yes.
Briefly the authors demonstrate the preservation of cellular architecture in human lung tissue at –5°C in electrostatic supercooled systems. Furthermore, the absence of single stranded DNA and the capacity for supercooled tissues to passively acquire immunoglobulin E (IgE) and subsequently produce cysteinyl-leukotrienes when exposed to IgE antibody suggets the preservation of cellular membrane integrity and limited apoptosis, both of which represent the sine quo non of freeze-thaw injury. Assessing post-thaw viability by additional measures of aerobic metabolism and gene transcription would provide further insight into the mechanism of supercooling. Interestingly, observations of anuran vertebrates that routinely freeze up to 70% of their body water at temperatures between –4C and –6C provide real world insights into the use of supercooling and organ graft preservation. Freezing tolerance is organ-specific with cardiac muscle particularly amenable to cryoprotection and transitions between cold dormant tissue states and "arousal" modulated by shifts between active and inactive states of regulatory enzymes [2]. The authors' ability to produce tissue viability in a supercooled state may provide unique opportunities to study the enzymology of hypothermic organ preservation rather than hypothermic organ injury.
Overall, the contributions of Abe and colleagues [1] are to be applauded. However, the goal of organ procurement is not preservation but transplantation and improvement in preservation without concomitant improvement in primary graft function and long-term allograft survival will have little clinical impact. The authors and those interested in similar technologies will have to demonstrate in clinical models the efficacy of supercooled allografts; their early observations on membrane integrity are an important and informative start. Hopefully, subsequent research will focus on the biophysics of electrostatic supercooling beyond such unsatisfying terms as "electrical pressure" and "microvibrations at the molecular level." It is interesting to speculate that the mechanism of electrostatic supercooling is structural stabilization of regulatory proteins and nucleic acids that are normally sensitive to the increasing concentration of intracellular electrolytes as cells dehydrate and osmoconcentrate with reduced temperatures. Although the concept of cryopreserved solid organ banks is a very distant reality, one suspects that there is much in the current technology for biomedicine in general and for cardiothoracic surgery in particular.
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References
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- Abe M, Jimi S, Hama H, et al. A novel method for preserving human lungs using a super-cooling system Ann Thorac Surg 2006;82:1085-1089.[Abstract/Free Full Text]
- Costanzo J, Lee RE. Cryoprotection by urea in a terrestrially hibernating frog J Exp Biol 2006;208:4079-4089.
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A Novel Method for Preserving Human Lungs Using a Super-Cooling System
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Ann. Thorac. Surg. 2006 82: 1085-1088.
[Abstract]
[Full Text]
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