Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study
- R K Kharbanda1,
- J Li2,
- I E Konstantinov2,
- M M H Cheung2,
- P A White3,
- H Frndova2,
- J Stokoe2,
- P Cox2,
- M Vogel4,
- G Van Arsdell2,
- R MacAllister4,
- A N Redington2
- 1University of Cambridge, Cambridge, UK
- 2The Hospital for Sick Children, Toronto, Ontario, Canada
- 3Papworth Hospital, Cambridge, UK
- 4University College London, London, UK
- Correspondence to:
Rajesh K Kharbanda
Harefield Hospital, Hill End Road, Uxbridge UB9 6JH, UK;
- Accepted 7 April 2005
- Published Online First 3 July 2006
Objectives: To test the hypothesis that remote ischaemic preconditioning (rIPC) reduces injury after cardiopulmonary bypass (CPB).
Design: Randomised study with an experimental model of CPB (3 h CPB with 2 h of cardioplegic arrest). Twelve 15 kg pigs were randomly assigned to control or rIPC before CPB and followed up for 6 h.
Intervention: rIPC was induced by four 5 min cycles of lower limb ischaemia before CPB.
Main outcome measures: Troponin I, glial protein S-100B, lactate concentrations, load-independent indices (conductance catheter) of systolic and diastolic function, and pulmonary resistance and compliance were measured before and for 6 h after CPB.
Results: Troponin I increased after CPB in both groups but during reperfusion the rIPC group had lower concentrations than controls (mean area under the curve −57.3 (SEM 7.3) v 89.0 (11.6) ng·h/ml, p = 0.02). Lactate increased after CPB in both groups but during reperfusion the control group had significantly more prolonged hyperlactataemia (p = 0.04). S-100B did not differ between groups. Indices of ventricular function did not differ. There was a tendency to improved lung compliance (p = 0.07), and pulmonary resistance changed less in the rIPC than in the control group during reperfusion (p = 0.02). Subsequently, peak inspiratory pressure was lower (p = 0.001).
Conclusion: rIPC significantly attenuated clinically relevant markers of myocardial and pulmonary injury after CPB. Transient limb ischaemia as an rIPC stimulus has potentially important clinical applications.
- avDo2, arteriovenous oxygen content difference
- CPB, cardiopulmonary bypass
- DC, direct current
- Fextr, extrapolated maximum flow at the beginning of the exhalation
- IR, ischaemia–reperfusion
- Poccl, pressure signal during occlusion
- PVR, pulmonary vascular resistance
- rIPC, remote ischaemic preconditioning
- Vextr, extrapolated exhaled volume
- V̇o2, oxygen consumption
This work was supported by a grant from the Canadian Institutes of Health Research. The British Heart Foundation supports RKK. MMHC is supported by the Heart and Stroke Foundation of Ontario, Canada