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Updated: May 1, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Delayed remote preconditioning induces cardioprotection: role of heme oxygenase-1
Chenghui Zhou1, Lihuan Li1, Huatong Li1
1Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Xicheng District, Beijing China.
Insights
Delayed remote ischemic preconditioning (DRIPC) protects the heart by increasing heme oxygenase-1 (HO-1) levels. More preconditioning stimuli enhance this protective effect, offering a potential therapeutic strategy for cardiac injury.
Area of Science:
- Cardiovascular Physiology
- Ischemic Heart Disease
- Molecular Cardiology
Background:
- The role of heme oxygenase-1 (HO-1) in delayed remote ischemic preconditioning (DRIPC)-induced cardioprotection remains unexplored.
- Investigating HO-1's involvement is crucial for understanding DRIPC's protective mechanisms against cardiac ischemia.
Purpose of the Study:
- To determine if HO-1 mediates the cardioprotective effects of DRIPC in an isolated perfused rat heart model.
- To assess the impact of varying DRIPC stimuli on HO-1 expression and cardioprotection.
Main Methods:
- Isolated rat hearts underwent 30 minutes of ischemia and 60 minutes of reperfusion.
- Delayed remote ischemic preconditioning (DRIPC) involved daily hind limb occlusion/reflow cycles for 1, 2, or 3 days prior to ischemia.
- Measurements included infarct size, troponin levels, cardiac function, and HO-1 protein/mRNA expression.
Main Results:
- DRIPC significantly improved post-ischemic cardiac function and reduced enzyme release.
- The infarct-limiting effect of DRIPC was dose-dependent, with 3 days (D3RIPC) showing the greatest reduction in infarct size.
- Inhibition of HO-1 with Zinc Protoporphyrin IX blocked DRIPC's protective effects, which correlated with increased HO-1 expression.
Conclusions:
- Heme oxygenase-1 (HO-1) plays a significant role in the cardioprotection afforded by delayed remote ischemic preconditioning (DRIPC).
- Increasing the number of DRIPC stimuli enhances cardioprotective benefits, associated with elevated HO-1 levels.
Background:
The role of heme oxygenase-1 (HO-1) in the cardioprotection induced by delayed remote ischemic preconditioning (DRIPC) has not been investigated. Therefore, this study was designed to investigate whether HO-1 is involved in DRIPC-mediated cardioprotection in an isolated perfused rat heart model.
Materials And Methods:
Isolated rat hearts were subjected to 30 min ischemia followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size, myocardial troponin levels, and heart function were measured. The protein and messenger RNA levels of HO-1 were determined.
Results:
DRIPC facilitated postischemic cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group (10.22 ± 2.57%) than the D1RIPC group (22.34 ± 4.02%, P < 0.001) or the D2RIPC group (14.60 ± 3.13%, P = 0.034). These effects in the D1RIPC group could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor). DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein expression (D1RIPC, 0.11 ± 0.03; versus 0.15 ± 0.06 in the D2RIPC group, P = 0.06; versus 0.20 ± 0.04 in the D3RIPC group, P = 0.04) and messenger RNA levels of HO-1 expression.
Conclusions:
Our findings suggest that HO-1 is involved in the cardioprotection induced by DRIPC, and that increase in the number of preconditioning stimuli may enhance cardioprotective effects accompanied with increased HO-1 level.
