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J Am Coll Cardiol, 2006; 47:2277-2282, doi:10.1016/j.jacc.2006.01.066 (Published online 12 May 2006).
© 2006 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: PEDIATRIC AND ADOLESCENT HEART DISEASE

Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning on Children Undergoing Cardiac Surgery

First Clinical Application in Humans

Michael M.H. Cheung, MB, ChB, MRCP, Rajesh K. Kharbanda, MD, PhD, Igor E. Konstantinov, MD, PhD, Mikiko Shimizu, MD, Helena Frndova, Meng, Jia Li, MD, PhD, Helen M. Holtby, MD, Peter N. Cox, MD, Jeffrey F. Smallhorn, MD, FRCP, Glen S. Van Arsdell, MD and Andrew N. Redington, MD, FRCP*

Divisions of Cardiology and Cardiovascular Surgery, Critical Care Medicine and Anaesthesia, Hospital for Sick Children, Toronto, Canada

Manuscript received November 8, 2005; revised manuscript received January 10, 2006, accepted January 16, 2006.

* Reprint requests and correspondence: Dr. Andrew Redington, Head, Division of Cardiology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada (Email: andrew.redington{at}sickkids.ca).

OBJECTIVES: We conducted a randomized controlled trial of the effects of remote ischemic preconditioning (RIPC) in children undergoing repair of congenital heart defects.

BACKGROUND: Remote ischemic preconditioning reduces injury caused by ischemia-reperfusion in distant organs. Cardiopulmonary bypass (CPB) is associated with multi-system injury. We hypothesized that RIPC would modulate injury induced by CPB.

METHODS: Children undergoing repair of congenital heart defects were randomized to RIPC or control treatment. Remote ischemic preconditioning was induced by four 5-min cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Measurements of lung mechanics, cytokines, and troponin I were made pre- and postoperatively.

RESULTS: Thirty-seven patients were studied. There were 20 control patients and 17 patients in the RIPC group. The mean age and weight of the RIPC and control patients were not different (0.9 ± 0.9 years vs. 2.2 ± 3.4 years, p = 0.4; and 6.9 ± 2.9 kg vs. 11.5 ± 10 kg, p = 0.06). Bypass and cross-clamp times were not different (80 ± 24 min vs. 88 ± 25 min, p = 0.3; and 55 ± 13 min vs. 59 ± 13 min, p = 0.4). Levels of troponin I postoperatively were greater in the control patients compared with the RIPC group (p = 0.04), indicating greater myocardial injury in control patients. Postoperative inotropic requirement was greater in the control patients compared with RIPC patients at both 3 and 6 h (7.9 ± 4.7 vs. 10.9 ± 3.2, p = 0.04; and 7.3 ± 4.9 vs. 10.8 ± 3.9, p = 0.03, respectively). The RIPC group had significantly lower airway resistance at 6 h postoperatively (p = 0.009).

CONCLUSIONS: This study demonstrates the myocardial protective effects of RIPC using a simple noninvasive technique of four 5-min cycles of lower limb ischemia and reperfusion. These novel data support the need for a larger study of RIPC in patients undergoing cardiac surgery.

Abbreviations and Acronyms
  A-a O2 = alveolar-arterial oxygen
  CPB = cardiopulmonary bypass
  ECG = electrocardiographic/electrocardiogram
  IL = interleukin
  IR = ischemia-reperfusion
  RIPC = remote ischemic preconditioning
  TNF = tumor necrosis factor




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