title: Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor.
abstract: Exercise protects against myocardial ischemia-reperfusion (I-R) injury but the mechanism remains unclear. Protection can be transferred from a remotely preconditioned human donor to an isolated perfused rabbit heart using a dialysate of plasma. We hypothesized that physical exercise preconditioning also confers cardioprotection through a humorally mediated effector dependent on opioid receptor activation. Thirteen male volunteers performed vigorous exercise (four 2-minute bouts of high-intensity exercise) and 1 week later they underwent remote ischemic preconditioning (four cycles of 5 min upper limb ischemia and reperfusion). Dialysates were prepared from blood collected before (control) and after the two interventions. Isolated rabbit hearts were perfused with the dialysates without and with co-administration of naloxone (opioid receptor antagonist) prior to 40 min regional ischemia and 2 h reperfusion. Exercise and remote ischemic preconditioning (rIPC) reduced infarct size from 60 ± 5 to 35 ± 5 % and from 57 ± 7 to 27 ± 3 % of the area at risk, respectively (p < 0.05 and < 0.01). Furthermore, post-ischemic left ventricular developed pressure was improved compared with controls (p = 0.08 for exercise and p = 0.04 for rIPC). Co-perfusion with naloxone abrogated the protective effects of exercise and remote ischemic preconditioned dialysates. In conclusion, high-intensity exercise preconditioning elicits cardioprotection through a humorally mediated dependent on opioid receptor activation, similar to rIPC.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Denmark. marie.m.michelsen@gmail.com
authors.forename: M M
authors.initials: MM
authors.lastname: Michelsen
authors.forename: N B
authors.initials: NB
authors.lastname: Støttrup
authors.forename: M R
authors.initials: MR
authors.lastname: Schmidt
authors.forename: B
authors.initials: B
authors.lastname: Løfgren
authors.forename: R V
authors.initials: RV
authors.lastname: Jensen
authors.forename: M
authors.initials: M
authors.lastname: Tropak
authors.forename: E Jean
authors.initials: EJ
authors.lastname: St-Michel
authors.forename: A N
authors.initials: AN
authors.lastname: Redington
authors.forename: H E
authors.initials: HE
authors.lastname: Bøtker
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001803:Blood Transfusion; D015444:Exercise; D006439:Hemodynamics; D006801:Humans; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning / Q000379:methods*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects; D011817:Rabbits; D013997:Time Factors; D034941:Upper Extremity / Q000098:blood supply*; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D019344:Lactic Acid; D009270:Naloxone