Prolonged 24-hour subzero preservation of heterotopically transplanted rat hearts using antifreeze proteins derived from arctic fish

Gabriel Amir, Boris Rubinsky, Liana Horowitz, Liron Miller, Jonathan Leor, Yigal Kassif, David Mishaly, Aram K. Smolinsky, Jacob Lavee

Research output: Contribution to journalArticlepeer-review

Abstract

Background Arctic fish survive subzero temperatures by producing a family of antifreeze proteins (AFPs) that noncolligatively lower the freezing temperature of their body fluids. We report 24-hour storage of mammalian hearts for transplantation at subzero temperatures using AFPs derived from arctic fish. Methods Forty-two heterotopic transplantations were performed in isoimmune Sprague-Dawley rats. Harvested hearts were retrogradely infused with cold 4°C University of Wisconsin (UW) solution and were preserved in a specialized cooling bath at two target temperatures, 4°C and -1.3°C for 12,18, and 24 hours (6 experiments/group). Preservation solutions were UW alone for the 4°C group, and UW with 15 mg/mL AFP III for the -1.3°C group. After hypothermic storage the hearts were heterotopically transplanted into isoimmune rats. Viability was assessed and graded on a scale of 0 to 6 (0 = no contractions to 6 = excellent contractions). Transplanted hearts were then fixed in vivo and were subject to electron microscopy and histopathologic examination. Results None of the hearts preserved at -1.3°C in UW/AFP III solution froze. All control hearts preserved at -1.3°C without AFP protection froze and died at reperfusion. Viability of hearts preserved at -1.3°C in UW/AFP III solution was significantly better after 18 hours of preservation, 30 and 60 minutes after reperfusion (median, 5 versus 3 and 6 versus 3, respectively; p < 0.05) and after 24 hours of preservation 30 and 60 minutes after reperfusion (median, 4.5 versus 1.5 and 5 versus 2, respectively; p < 0.05). Histologic and electron microscopy studies demonstrated better myocyte structure and mitochondrial integrity preservation with UW/AFP III solution. Conclusions Antifreeze proteins prevent freezing in subzero cryopreservation of mammalian hearts for transplantation. Subzero preservation prolongs ischemic times and improves posttransplant viability.

Original languageEnglish
Pages (from-to)1648-1655
Number of pages8
JournalAnnals of Thoracic Surgery
Volume77
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • 34

Fingerprint

Dive into the research topics of 'Prolonged 24-hour subzero preservation of heterotopically transplanted rat hearts using antifreeze proteins derived from arctic fish'. Together they form a unique fingerprint.

Cite this