Original Contribution EXERCISE, ANTIOXIDANTS, AND HSP72: PROTECTION AGAINST MYOCARDIAL ISCHEMIA/REPERFUSION KARYN L. HAMILTON,* JESSICA L. STAIB,* TRACEY PHILLIPS,* ANDREA HESS,* SHANNON L. LENNON,* and SCOTT K. POWERS* † *Department of Exercise and Sport Science and † Department of Physiology, Center for Exercise Science, University of Florida, Gainesville, FL, USA (Received 2 July 2002; Revised 11 December 2002; Accepted 12 December 2002) Abstract—Endurance exercise is associated with protection against myocardial ischemia/reperfusion (I/R) injury and has been shown to increase heat shock protein 72 (HSP72). Dietary antioxidants have also been reported to decrease I/R-induced injury. Because exercise and antioxidants may provide cardioprotection via different mechanisms, com- bining these countermeasures could provide additive protection. Alternatively, because exercise-induced oxidant production may promote expression of HSP72, antioxidants could attenuate exercise-induced HSP72 expression and decrease exercise-related cardioprotection. These experiments examined the individual and combined effects of exercise and antioxidants on myocardial I/R injury (in vivo). Rats receiving a mixed antioxidant diet or control diet were assigned to exercise or sedentary groups and randomized to receive: (i) short I/R (myocardial stunning), (ii) long I/R (myocardial infarction), or (iii) sham surgery. Antioxidants significantly increased total antioxidant capacity and attenuated exercise- related HSP72 accumulation. Nonetheless, during short I/R, exercise-trained animals demonstrated improved left ventricular developed pressure (LVDP), independent of diet. Further, antioxidants alone resulted in improved LVDP. Finally, compared to control diet/sedentary animals, both exercise groups (control and antioxidant diets) and the antioxidant diet/sedentary group sustained smaller infarctions. We conclude that exercise and antioxidants can inde- pendently provide protection against myocardial contractile dysfunction and infarction, and the combination of these two strategies does not enhance or inhibit the protection observed with each individual countermeasure. © 2003 Elsevier Science Inc. Keywords—Heat shock proteins, Reactive oxygen species, Lipid peroxidation, Stunning, Infarction, Free radicals INTRODUCTION Myocardial ischemia/reperfusion (I/R) can lead to ionic imbalances, activation of proteases, oxidative injury, and ultimately cardiac cell death. Hence, developing coun- termeasures to protect the myocardium from I/R injury is important. In this regard, evidence indicates that several members of the heat shock protein (HSP) family can provide myocardial protection against cellular stress. Specifically, HSP72 has been shown to protect cells from I/R injury [1–3]. Perhaps the most convincing evidence that HSP72 provides cardioprotection is provided by transgenic mice overexpressing HSP72 with improved postischemic contractile function and decreased infarc- tion size [4,5]. Endurance exercise is a pragmatic means of elevating myocardial levels of HSP72 and, importantly, exercise training is also associated with cardioprotection during I/R [1– 4]. While the exercise-induced cellular signals respon- sible for increased expression of myocardial HSP72 con- tinue to be investigated, an increased production of reactive oxygen species (ROS) has been postulated to play a prom- inent role [6 –13]. Although ROS regulate several redox- signaling pathways in healthy cells, it is also clear that high levels of ROS contribute to numerous pathologies including I/R injury [14]. Therefore, dietary antioxidants could act as another countermeasure to protect the myocardium against I/R injury [15,16]. While the specific mechanism(s) by which exercise provides cardioprotection continues to be investigated Address correspondence to: Dr. Karyn L. Hamilton, University of Florida, Center for Exercise Science, P.O. Box 118206, Gainesville, FL 32611, USA; Tel: (352) 392-9575; Fax: (352) 392-0316; E-Mail: khamilton@hhp.ufl.edu. Free Radical Biology & Medicine, Vol. 34, No. 7, pp. 800 – 809, 2003 Copyright © 2003 Elsevier Science Inc. Printed in the USA. All rights reserved 0891-5849/03/$–see front matter doi:10.1016/S0891-5849(02)01431-4 800