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J Thorac Cardiovasc Surg 2003;126:133-142
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Protection of the human heart with ischemic preconditioning during cardiac surgery: role of cardiopulmonary bypass

^a Department of Integrative Human Cardiovascular Physiology and Cardiac Surgery, University of Leicester, Glenfield Hospital, Leicester, United Kingdom

Received for publication April 15, 2002; accepted for publication July 15, 2002.

^* Address for reprints: Professor M. Galiñanes, Department of Integrative Human Cardiovascular Physiology and Cardiac Surgery, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, United Kingdom (E-mail: sudip.ghoshglenfield-tr.trent.nhs.uk).

OBJECTIVE: Studies on the effects of ischemic preconditioning in the human heart have yielded conflicting results and therefore remain controversial. This study investigated whether ischemic preconditioning was able to protect against myocardial tissue damage in patients undergoing coronary artery surgery with cardiopulmonary bypass and on the beating heart.

METHODS: A total of 120 patients were studied and divided into 3 groups: group I: cardiopulmonary bypass with intermittent crossclamp fibrillation; group II: cardiopulmonary bypass with cardioplegic arrest using cold blood cardioplegia; group III: surgery on the beating heart. In each group (n = 40), patients were randomly subdivided (n = 20/subgroup) into control and preconditioning groups (1 cycle of 5 minutes of ischemia/5 minutes reperfusion before intervention). Ischemic preconditioning was induced by clamping the ascending aorta in groups I and II or by clamping the coronary artery in group III. Serial venous blood levels of troponin T were analyzed before surgery and at 1, 4, 8, 24, and 48 hours after termination of ischemia. In addition, in vitro studies using right atrial specimens obtained before the institution of cardiopulmonary bypass, and then again 10 minutes after initiation of bypass, were performed. The specimens were equilibrated for 30 minutes before being allocated to 1 of the following 2 groups (n = 6 per group): (1) ischemia alone (90 minutes of ischemia followed by 120 minutes of reoxygenation) or (2) preconditioning with 5 minutes of ischemia and 5 minutes of reoxygenation before the long ischemic insult. Creatine kinase leakage (U/g wet weight) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction (mmol/l per gram wet weight), an index of cell viability, were assessed at the end of the experiment.

RESULTS: There were no perioperative myocardial infarctions or deaths in any of the groups studied. The total release of troponin T was similar in groups I and II (patients undergoing surgery with cardiopulmonary bypass) and in the release profile; they were unaffected by ischemic preconditioning. In contrast, the total troponin T release for the first 48 hours was significantly reduced by ischemic preconditioning in group III (patients undergoing surgery without cardiopulmonary bypass) from 3.1 ± 0.1 to 2.1 ± 0.2 ng · h · mL. Furthermore, the release profile that peaked at 8 hours in the control group shifted to the left at 1 hour. In the in vitro studies, the atrial muscles obtained before cardiopulmonary bypass were protected by ischemic preconditioning (creatine kinase = 2.6 ± 0.2 and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction = 152 ± 24 vs creatine kinase = 5.4 ± 0.6 and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction = 87 ± 16 in controls; P < .05); however, the muscles obtained 10 minutes after initiation of cardiopulmonary bypass were already protected (creatine kinase = 0.8 ± 0.1 and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction = 316 ± 38), and ischemic preconditioning did not result in further improvements.

CONCLUSIONS: Ischemic preconditioning is protective in patients undergoing coronary artery surgery on the beating heart without the use of cardiopulmonary bypass, but it offers no additional benefit when associated with bypass regardless of the mode of cardioprotection used, because cardiopulmonary bypass per se induces preconditioning.

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