Repeated physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats
Shiro Hoshida, MD, PhD* ,*,
Nobushige Yamashita, MD, PhD,
Kinya Otsu, MD, PhD and
Masatsugu Hori, MD, PhD
* Division of Cardiology, Osaka Rosai Hospital, Sakai, Japan
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan
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Figure 1 Experimental protocol for five repeated-stress groups. After two sessions of exercise, whole-body hyperthermia or tumor necrosis factor (TNF)-alpha injections, performed at an interval of 48 h, the rats were subjected to 20 min of left coronary artery occlusion, followed by 48 h of reperfusion. The interval between the second stimulus and ischemia was between 0.5 and 168 h. The incidence of ventricular fibrillation during ischemia and the size of myocardial infarction after reperfusion were then examined. Although not shown, in rats subjected to a single stress (three single-stress groups), the rats were subjected to 20 min of left coronary artery occlusion, followed by 48 h of reperfusion after one episode of exercise, whole-body hyperthermia or TNF-alpha injection. The interval between the single-stress stimulus and ischemia was between 0.5 and 120 h. Myocardial manganese superoxide dismutase activity was measured 0.5 to 120 h after the single-stress stimulus (single-stress group) or 0.5 to 168 h after the second-stress stimulus (repeated-stress group).
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Figure 2 The effects of a single session of a sublethal stimulus and the recovery interval on the size of the myocardial infarct (open bars; mean ± SEM) and the incidence of ventricular fibrillation (VF) (solid lines; upper panels) and manganese superoxide dismutase (Mn-SOD) activity (lower panels) in rat myocardium. Between five and nine rats were included in each group. "C" indicates the values for control rats that did not receive a sublethal stimulus. *p < 0.05 vs. control rats.
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Figure 3 The effects of two episodes of sublethal stimuli and the recovery interval on the size of the myocardial infarct (open bars; mean ± SEM) and the incidence of ventricular fibrillation (VF) (solid lines). Between 7 and 10 rats were included in each group. "S" indicates the values for sham-control rats that did not receive sublethal stimuli. *p < 0.05 vs. sham-control rats. TNF- = tumor necrosis factor-alpha.
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Figure 4 The effects of two episodes of sublethal stimuli and the recovery interval on manganese superoxide dismutase (Mn-SOD) activity in rat myocardium. Five or six rats were included in each group. "S" indicates the values for sham-control rats that did not receive sublethal stimuli. Data are expressed as the mean value ± SEM. *p < 0.05 vs. sham-control rats.
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