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J Am Coll Cardiol, 2002; 40:826-831
© 2002 by the American College of Cardiology Foundation
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EXPERIMENTAL STUDY

Repeated physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats

Shiro Hoshida, MD, PhD*{dagger},*, Nobushige Yamashita, MD, PhD{dagger}, Kinya Otsu, MD, PhD{dagger} and Masatsugu Hori, MD, PhD{dagger}

* Division of Cardiology, Osaka Rosai Hospital, Sakai, Japan
{dagger} Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan

Manuscript received June 12, 2001; revised manuscript received April 19, 2002, accepted May 20, 2002.

* Reprint requests and correspondence: Dr. Shiro Hoshida, Vice Director, Yao Municipal Hospital, 2-1-55 Minami-Taishido, Yao, Osaka 581-0056, Japan.
hoshidas{at}city.yao.osaka.jp

OBJECTIVES: We investigated the time course of myocardial tolerance to ischemia-reperfusion injury after repeated physiologic or pharmacologic stresses.

BACKGROUND: Sublethal stress provides cardiac tolerance to ischemia-reperfusion injury and increases the activity of manganese superoxide dismutase (Mn-SOD) in the myocardium in a biphasic manner. However, few studies have investigated the time course of the cardioprotective effects after repeated stresses.

METHODS: One or two episodes of the same physiologic or pharmacologic stress (exercise, whole-body hyperthermia, or tumor necrosis factor-alpha treatment), or a combination of two different types of stress, were induced after a 48-h interval. The rats were then subjected to 20 min of left coronary artery occlusion, followed by 48 h of reperfusion. The interval between the last stimulus and the induced ischemia was between 0.5 h and 168 h. The incidence of ventricular fibrillation during ischemia and the size of the myocardial infarct after reperfusion were then examined.

RESULTS: When two episodes of physiologic or pharmacologic stress were induced, the beneficial effects against ischemia-reperfusion injury were observed in a monophasic manner. These effects persisted for a period of 0.5 to 60 h. One episode of sublethal stress provoked the same beneficial effects, but in a biphasic manner. The increase in Mn-SOD activity in the cardiac tissue resembled the time course for cardioprotection against ischemia-reperfusion injury.

CONCLUSIONS: Two episodes of physiologic or pharmacologic stress can provide persistent cardioprotective effects against ischemia-reperfusion injury.

Abbreviations and Acronyms
  MI
  myocardial infarction
  Mn-SOD
  manganese superoxide dismutase
  TNF
  tumor necrosis factor
  VF
  ventricular fibrillation




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