Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor

• Published in: Basic research in cardiology Vol. 107; no. 3; pp. 260 - 9
• Main Authors: Michelsen, M. M., Støttrup, N. B., Schmidt, M. R., Løfgren, B., Jensen, R. V., Tropak, M., St-Michel, E. Jean, Redington, A. N., Bøtker, H. E.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2012; Springer Nature B.V
• Subjects: Adolescent; Adult; Animals; Blood Transfusion; Cardiology; Exercise; Hemodynamics; Humans; In Vitro Techniques; Ischemic Preconditioning - methods; Lactic Acid - metabolism; Male; Medicine; Medicine & Public Health; Myocardial Infarction - blood; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - blood; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Original Contribution; Paracrine Communication - drug effects; Rabbits; Time Factors; Upper Extremity - blood supply; Ventricular Function, Left; Ventricular Pressure; Young Adult; Remote ischemic preconditioning; Reperfusion; Cardioprotection; Exercise; Ischemia; Humoral factor
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s00395-012-0260-x

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.