Objective Recent investigations demonstrate that ischaemic preconditioning and post-conditioning can reduce infarct size to the same degree. After reflow, opening of the mitochondrial permeability transition pore (mPTP) has been involved in lethal reperfusion injury. We hypothesised that the combination of ischaemic preconditioning and post-conditioning would result in greater preservation of myocardium by offering additional effect on modulating mPTP opening.
Methods Anesthetized open-chest rabbits underwent 1.5-h regional ischaemia/1.5-h reperfusion and were divided into four groups: control(C), preconditioning (Pre-con), gradual reperfusion (GR), and preconditioning plus gradual reperfusion (Pre-con+ GR). Control hearts underwent no additional intervention. Preconditioning consisted of three cycles of 5 min of ischaemia and 5 min of reperfusion before the 1.5-h ischaemia. Gradual reperfusion hearts underwent 5 stages involving 10-s occlusion/50-s reperfusion, 20-s occlusion/40-s reperfusion, 30-s occlusion/30-s reperfusion, 40-s occlusion/20-s reperfusion, 50-s occlusion/10-s reperfusion starting 10 s after release of the index coronary occlusion. Preconditioning plus gradual reperfusion performed both interventions in preconditioning and gradual reperfusion. 1.5 h reperfusion later, mitochondria were isolated from the risk region myocardium, and mPTP opening was determined by using the mPTP kinetics method.
Results Preconditioning, and gradual reperfusion alone significantly limited infarct size, which averaged 7.21±4.76%, 5.36±1.90% of left ventricular weigh, respectively, versus 11.94±3.75% in controls (p<0.05 vs control). Preconditioning plus gradual reperfusion averaged 7.53±3.45% of left ventricular weigh offering no greater effect than preconditioning or gradual reperfusion alone (p>0.05). The t1/2 of mPTP kinetics averaged 5.37±4.76 min, 5.27±4.76 min, in preconditioning and gradual reperfusion, respectively, significantly higher than the value of 5.06±4.76 min in controls (p<0.05). The t1/2 of mPTP kinetics averaged 6.62±4.76 min in preconditioning plus gradual reperfusion, however, has no more effect than preconditioning or gradual reperfusion alone (p>0.05).
Conclusions The combination of ischaemic preconditioning and gradual reperfusion has no greater effect on mitochondrial permeability pore but provides more powerful anti-ischaemic protection than either intervention alone.
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