Naloxone blocks transferred preconditioning in isolated rabbit hearts.
We have shown that the cardioprotective benefits of ischemic preconditioning (PC) can be transferred from PC to virgin acceptor hearts via coronary effluent transfusion, implicating the presence of hormonal preconditioning factor(s). Using isolated buffer-perfused rabbit hearts, our aims were to: (1) determine whether the protective factor(s) could be concentrated and recovered by reverse phase chromatography and (2) whether opioid receptor activation contributes to this transferred cardioprotection. Material released into the coronary effluent during PC ischemia/reperfusion or normoxic perfusion was concentrated by reverse phase chromatography. In phase one, hearts received no intervention (controls), PC ischemia, concentrate generated from normoxic hearts (normoxic acceptors) or concentrate from PC hearts (PC acceptors). All hearts underwent 40 min of global ischemia, and area of necrosis (AN) was delineated by tetrazolium staining. In phase two, three additional groups of hearts (control, PC and PC acceptors) received the opioid antagonist naloxone (2 microM) throughout the intervention phase. Treatment with normoxic concentrate had no effect on infarct size: (AN: normoxic acceptors 39+/-8%; control 42+/-8%). In contrast, treatment with PC concentrate evoked cardioprotection equivalent to that afforded by conventional PC (AN 19+/-5% and 21+/-6% respectively P<0.05 v control). Naloxone had no effect on infarct size in controls, and did not inhibit preconditioning. However, naloxone abrogated the protection achieved by transfer of PC concentrate (AN: 44+/-7%). These results indicate that PC concentrate evokes a cardioprotective effect via a mechanism requiring an intact opioid receptor system.
Dickson
E W
EW
Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. dicksone@ummhc.org
Blehar
D J
DJ
Carraway
R E
RE
Heard
S O
SO
Steinberg
G
G
Przyklenk
K
K
D000818:Animals; D004743:Enkephalin, Leucine / Q000378:metabolism / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009270:Naloxone / Q000494:pharmacology*; D011817:Rabbits; D011863:Radioimmunoassay; D011897:Random Allocation
D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine