Use of "natural" hibernation induction triggers for myocardial protection.
BACKGROUND
Hypothermic cardioplegia provides adequate myocellular protection, yet stunning and dysfunction remain significant problems. Interestingly, the subcellular changes of hibernation parallel the altered biology of induced cardiac ischemia, but are well tolerated by hibernating mammalian myocardium. Hibernation induction trigger (HIT) from winter-hibernating animal serum induces hibernation in active animals. Hibernation induction trigger is opiate in nature and is similar to the delta 2 opioids.


METHODS
To determine whether HIT could improve myocardial recovery following global ischemia, we gave 37 isolated rabbit hearts either standard cardioplegia or cardioplegia containing summer-active woodchuck, hibernating woodchuck, or black bear HIT serum or a delta 2 opioid, D-Ala2-Leu5-enkephalin, before 2 hours of global ischemia.


RESULTS
Hibernation induction trigger appeared not to have an active mechanism during ischemia, as all hearts had equal recovery. In contrast, when examining for a preischemia mechanism, 23 additional rabbits received 3 days pretreatment with summer-active woodchuck or HIT hibernating woodchuck or black bear serum, or were preperfused with D-Ala2-Leu5-enkephalin or D-pen2,5-enkephalin, a-delta 1 opioid, again before 2 hours of global ischemia. Postischemic ventricular function, coronary flows, myocardial oxygen consumption, and ultrastructural preservation were all significantly improved with HIT and D-Ala2-Leu5-enkephalin pretreatment.


CONCLUSIONS
"Natural" HIT protection is superior to standard cardioplegia alone and may have clinical application.
Bolling
S F
SF
Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, USA. sbolling@umich.edu
Tramontini
N L
NL
Kilgore
K S
KS
Su
T P
TP
Oeltgen
P R
PR
Harlow
H H
HH
D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D006605:Hibernation / Q000502:physiology*; D007036:Hypothermia, Induced; D008297:Male; D008392:Marmota; D017202:Myocardial Ischemia / Q000503:physiopathology; D017682:Myocardial Stunning / Q000209:etiology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides; D011292:Premedication; D011506:Proteins / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology*; D011817:Rabbits; D017465:Receptors, Opioid, delta / Q000819:agonists; D001503:Ursidae; D016276:Ventricular Function / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D004745:Enkephalins; D010455:Peptides; D011506:Proteins; D017465:Receptors, Opioid, delta; C036932:hibernation induction trigger; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-