Repeated physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats.
OBJECTIVE
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.
Division of Cardiology, Osaka Rosai Hospital, Sakai, Japan. hoshidas@city.yao.osaka.jp
Shiro
S
Hoshida
Nobushige
N
Yamashita
Kinya
K
Otsu
Masatsugu
M
Hori
D000818:Animals; D006979:Hyperthermia, Induced; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*
D014409:Tumor Necrosis Factor-alpha