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Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents
Published on: June 2, 2015
Limb ischemic preconditioning reduces heart and lung injury after an open heart operation in infants
Wenwu Zhou1, Debing Zeng, Renwei Chen
1Department of Cardiothoracic Surgery, Hunan Children's Hospital, Changsha, Hunan, China. acrophober@163.com
Insights
Limb remote ischemic preconditioning (RIPC) is a safe and feasible method for infants undergoing heart surgery. RIPC effectively reduces heart and lung injury caused by ischemia-reperfusion, with heat shock protein 70 playing a key role.
Area of Science:
- Cardiovascular Surgery
- Pediatric Cardiology
- Ischemia-Reperfusion Injury
Background:
- Open heart surgery with cardiopulmonary bypass often leads to heart and lung ischemia-reperfusion injury (IRI).
- Limb remote ischemic preconditioning (RIPC) is a technique that has shown promise in reducing IRI in various organs.
Purpose of the Study:
- To assess the feasibility and safety of limb RIPC in infants undergoing congenital heart defect repair.
- To evaluate the protective effects of limb RIPC against myocardial and pulmonary IRI in this patient population.
Main Methods:
- A prospective, randomized, controlled clinical trial involving 60 infants undergoing ventricular septal defect repair.
- RIPC was administered twice preoperatively via induced ischemia-reperfusion cycles in the upper arm.
- Measurements included lung compliance, respiratory index, cardiac inotropic score, serum inflammatory markers, cardiac enzymes, oxidative stress markers, and heat shock protein 70 expression.
Main Results:
- Limb RIPC was safely and easily applied in infants, with no reported limb complications.
- RIPC group showed improved lung compliance and reduced cardiac inotropic scores postoperatively.
- RIPC attenuated the systemic inflammatory response and reduced cardiac enzyme leakage, with increased heat shock protein 70 expression in cardiomyocytes.
Conclusions:
- Limb RIPC is a safe and feasible intervention for infants undergoing congenital heart surgery.
- RIPC effectively mitigates myocardial and pulmonary ischemia-reperfusion injury in infants.
- Heat shock protein 70 upregulation is implicated in the protective mechanism of RIPC.
Abstract:
Open heart surgery supported by cardiopulmonary bypass is associated with heart and lung ischemia-reperfusion injury (IRI). Limb remote ischemic preconditioning (RIPC) reduces injury caused by ischemia-reperfusion in multiple distant organs. We conducted a prospective clinical trial (randomized and controlled) to test the feasibility and safety of limb RIPC, as well as its protective effects against myocardial and pulmonary IRI for infants undergoing repair of simple congenital heart defects. Infants undergoing repair of ventricular septal defects were enrolled in our study and randomly assigned to one of two treatment groups: limb RIPC or control. RIPC was induced twice (24 h and 1 h preoperatively) via three 5-min cycles of ischemia and reperfusion on the left upper arm using a blood pressure cuff. Lung compliance, respiratory index (RI), and cardiac inotropic score (IS) were calculated for each patient. Serum concentrations of the following factors were measured perioperatively: interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha; lactate dehydrogenase (LDH), creatine kinase (CK), and its isoenzyme (CK-MB), and troponin I (TnI); malondialdehyde (MDA) and superoxide dismutase (SOD). The expression of heat shock protein 70 (HSP 70) in cardiomyocytes was analyzed by Western blot. Surgical outcomes, including limb movement and sensory function, were recorded in detail. Sixty infants weighting less than 7 kg were studied, with 30 patients in the RIPC group and 30 in the control group. Within 6 months of discharge from the hospital, no limb disability, sensory disturbance, or other surgical complications were found in any patient. Compared with the control group, patients in the RIPC group had higher Cs and Cd, along with lower RI and IS at various postoperative phases. At the beginning of the operation, serum concentrations of IL-6, IL-8, IL-10, TNF-alpha, LDH, CK, and TnI were higher in the RIPC group than the control group. Postoperatively, release of cytokines and leakage of heart enzymes were attenuated in the RIPC group; serum concentrations of cytokines and heart enzymes were lower in the RIPC group at some, but not all, postoperative time points. Furthermore, the RIPC group had lower coronary sinus venous concentrations of MDA and higher concentrations of SOD. Similarly, the expression of HSP 70 was upregulated in cardiomyocytes from the RIPC group. Limb RIPC can be applied safely and easily in infants, can attenuate systemic inflammatory response syndrome, and can increase systemic tolerance to IRI, imparting a protective effect against myocardial and pulmonary IRI. The expression of HSP 70 has an important role in the mechanism of action for RIPC.

