Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition

Objective: Diminishing oxidative stress may protect the heart against ischa emia-reperfusion injury by preventing opening of the mitochondrial permeabi lity transition (MPT) pore. The general anaesthetic agent propofol, a free radical scavenger, has been investigated for its effect on the MPT and its cardioprotective action following global and cardioplegic ischaemic arrest. Method: Isolated perfused Wister rat hearts were subjected to either warm global ischaemia (Langendorff) or cold St. Thomas' cardioplegia (working he art mode) in the presence or absence of propofol. MPT pore opening was dete rmined using [H-3]-2-deoxyglucose-6-phosphate ([H-3]-DOG-6P) entrapment. Th e respiratory function of isolated mitochondria was also determined for evi dence of oxidative stress. Results: Propofol (2 mu g/ml) significantly impr oved the functional recovery of Langendorff hearts on reperfusion (left ven tricular developed pressure from 28.4+/-6.2 to 53.3+/-7.3 mmHg and left ven tricular end diastolic pressure from 52.9+/-4.3 to 37.5+/-3.9 mmHg). Recove ry was also improved in propofol (4 mu g/ml) treated working hearts followi ng cold cardioplegic arrest. External cardiac work on reperfusion improved from 0.42+/-0.05 to 0.60+/-0.03 J/s, representing 45-64% of baseline values , when compared to controls (P<0.05). Propofol inhibited MPT pore opening d uring reperfusion, [H-3]-DOG-6P entrapment being 16.7 vs. 22.5 ratio units in controls (P<0.05). Mitochondria isolated from non-ischaemic, propofol-tr eated hearts exhibited increased respiratory chain activity and were less s ensitive to calcium-induced MPT pore opening. Conclusion: Propofol confers significant protection against global normothermic ischaemia and during col d cardioplegic arrest. This effect is associated with less opening of mitoc hondrial MPT pores, probably as a result of diminished oxidative stress. Pr opofol may be a useful adjunct to cardioplegic solutions in heart surgery. (C) 2000 Elsevier Science B.V. All rights reserved.