Mechanism Of Propofol Protects Against Cardioplegic Arrest-induced Apoptosis In Human

Several myocardial stresses occurring during cardiac surgery (CS), including ischemia and ischemia-reperfusion(IR),inflammatory response, operative trauma, cardioplegia and oxidative stress have been reported to trigger myocyte death. Both experimental and clinical studies have demonstrated that transient reversible myocardial ischemia in various settings, such as cardioplegia and cardiopulmonary bypass(CPB) during CS , leads to prolonged depression of cardiac contractility. (myocardial stunning). myocardial apoptosis may be involve in the pathogenesis of stunning and most importantly of persistent myocardial dysfunction after CS. Apoptosis or programmed cell death is a highly regulated and energy-requiring process. In cells subjected to pathologic stresses such as ischemia there is a delicate balance between survival and death. Membrane death receptor signaling pathway , mitochondrial release of mediators, balance of pro-apoptotic bax and antiapoptic bcl-2protein expression , and caspase8, 9 and 3 activation degree are involved in this balance. The anaesthetic propofol is frequently used during cardiac surgery and in postoperative sedation . It acts as a free radical scavenger and may also inhibit plasma membrane calcium channels. Use of propofol ,known to enhance PTP(Mitochondrial Permeability Transition) closure. improved cardioprotection during cardioplegia arrest. Propofol inhibited the ischemia-induced increase of the apoptosis-promoting protein Bax, in addition ,propofol stimulated the synthesis of the apoptosis-inhibiting protein Bcl-2. As a antiapoptosis agent, Mechanism of propofol protects against cardioplegic arrest-induced apoptosis relates to the mitochondrial pathway . The effects of propofol on Fas/FasL have not been studied during cardioplegia arrestObjectTo evaluate the effects of propofol on cardioplegic arrest (CA)-induced myocardiocyte apoptosis and its effect on regulation of Fas, Fasl expression,Caspase-3 activity in the right atria.MethodsThirty patient undergoing the operation of heart double valve replacement( DVR), were randomly divided into control and propofol treated groups (n=15 respectively),propofol treated group maintained 3. 5ug. ml by TCI pump, in control group received midazolam ,Tissue from right atriawas removed before and after cardioplegic arrest . HE staining was studied, In situ nick end-labeling (TUNEL)technique was used to detect the apoptotic cells, the expression of Fas, Fasl , activity of caspase-3 was studied by ABC immunohistochemistry.ResultThere were no significant preoperative or operative difference between groups. after CA, HE staining reveal that there was no visible myocardiocyte necrosis in heart, histologic score showed no significant difference between groups (0.6 ± 0. 52 vs 0.75 ± 0.54 p>0. 05) .but the number of apoptotic cells in propofol treated group was significantly decreased compared with the control group (10. 90±1.45% vs 19. 30 ± 3. 53% P<0. 05). . The caspase-3 activity in the propofol treated group was also significantly reduced compared with the control group (2. 65 ± 0. 67 vs 4. 60 ± 0.77 P <0. 05). The expression of Fas and Fasl were not significantly downregulated between propofol treated group and control (P>0. 05)ConclusionCardioplegia is a potent stimulus for induction of apoptosis. Propofol significantly reduces CA induced cardiomyocyte apoptosis and inhibits caspase-3 activity in human hearts and a mechanistic role is not associated with downregulation of Fas and Fasl expression...