title: The use of hibernation induction triggers for cardiac transplant preservation.
abstract: Cardiac transplant is hindered by donor shortage and preservation time. Extended extracorporeal preservation could increase the number and distribution of hearts for transplantation. Interestingly, mammalian hibernation biology closely parallels the altered cardiac cellular physiology noted with hypothermic organ storage. The present study undertook to test whether treatment with hibernation induction triggers could improve myocardial functional recovery following prolonged ischemic storage in a nonhibernating mammalian model. To study this hypothesis, isolated rabbit hearts had baseline functional and metabolic parameters recorded and then received either hypothermic storage only or standard cardioplegia, or cardioplegia containing 1 mg/kg D-Ala2-Leu5-enkaphalin (DADLE), which mimics natural hibernation, or preperfusion with DADLE, administered for 15 min at 2 mmol, 25 min prior to cardioplegic ischemia. Hearts were then subjected to 18 hr of global ischemic storage at 4 degrees C. Isovolumic developed pressure, coronary flows, and myocardial oxygen consumption were significantly improved with DADLE pretreatment vs. all groups after storage and reflow. Furthermore, DADLE hearts demonstrated better histological ultrastructure preservation following prolonged storage ischemia. This study demonstrates that hibernation protection with DADLE is beneficial for prolonged cardiac storage. The use of hibernation induction triggers is promising for organ preservation and deserve further mechanistic study.
authors.affiliation: Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor 48109-0344, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Bolling
authors.forename: T P
authors.initials: TP
authors.lastname: Su
authors.forename: K F
authors.initials: KF
authors.lastname: Childs
authors.forename: X H
authors.initials: XH
authors.lastname: Ning
authors.forename: N
authors.initials: N
authors.lastname: Horton
authors.forename: K
authors.initials: K
authors.lastname: Kilgore
authors.forename: P R
authors.initials: PR
authors.lastname: Oeltgen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002314:Cardioplegic Solutions; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation / Q000502:physiology*; D006605:Hibernation; D008297:Male; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009926:Organ Preservation / Q000379:methods*; D011817:Rabbits; D013997:Time Factors
chemical_list: D002314:Cardioplegic Solutions; D016308:Enkephalin, Leucine-2-Alanine