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 ischaemia-reperfusion injury by preventing opening of the mitochondrial permeability 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 heart mode) in the presence or absence of propofol. MPT pore opening was determined using [H-3]-2-deoxyglucose-6-phosphate ([H-3]-DOG-6P) entrapment. The respiratory function of isolated mitochondria was also determined for evidence of oxidative stress. Results: Propofol (2 mu g/ml) significantly improved the functional recovery of Langendorff hearts on reperfusion (left ventricular developed pressure from 28.4+/-6.2 to 53.3+/-7.3 mmHg and left ventricular end diastolic pressure from 52.9+/-4.3 to 37.5+/-3.9 mmHg). Recovery was also improved in propofol (4 mu g/ml) treated working hearts following 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 during 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-treated hearts exhibited increased respiratory chain activity and were less sensitive to calcium-induced MPT pore opening. Conclusion: Propofol confers significant protection against global normothermic ischaemia and during cold cardioplegic arrest. This effect is associated with less opening of mitochondrial MPT pores, probably as a result of diminished oxidative stress. Propofol may be a useful adjunct to cardioplegic solutions in heart surgery. (C) 2000 Elsevier Science B.V. All rights reserved.