Perioperative Cerebral And Cardiac Protective Effects Of Nicorandil, A Mitochondrial K_ATP Channel Opener, On Patients Undergoing On-pump Coronary Artery Bypass Graft

Objective To investigate whether nicorandil, a mitochondrial K_atp channel opener, has perioperative cardiac and cerebral protective effects in patients undergoing on-pump coronary artery bypass graft (CABG).Methods Thirty ASA II or III patients undergoing elective on-pump CABG were randomized to the nicorandil group (Group N, n=15) , in which patients received 10mg nicorandil orally 30 minutes before anesthesia, and the control group (Group C, n=15) in which patients did not receive nicorandil. Every patient underwent the Mini-mental state examination (MMSE) 24h before and after CABG. Blood cTnI, NSE, S100 β concentrations were tested by ELISA method precisely before induction (T₁) , 30 min after cardiopulmonary bypass (T₂) , 6 h after the surgery (T₃) and 24 h after the surgery (T₄) . Blood CKMB and CKII concentrations were measured preoperatively and postoperatively. Heart rate(HR), mean arterial blood pressure(MAP), pulmonary capillary wedge pressure(PCWP) and central venous pressure(CVP) were recorded at the beginning of operation (t₁), immediately after termination of CPB (t₂), 30 min after termination of CPB (t₃), 60 min after termination of CPB (t₄) and at the end of operation (t₅). Cardiac index (CI), stroke volume index (SI), left ventricular-stroke work index (LVSWI), right ventricular-stroke work index (RVSWI), systematic vascular resistance (SVR), pulmonary vascular resistance (PVR) at these time points were calculated. ECG was monitored throughout operation to screen new arrhythmia that occurred after CPB.Results Blood cTnI concentration increased significantly after CPB (P<0.01) in Group C, while remained quite stable in Group N. A smaller increment of blood cTnI concentration at T₄ was found in Group N than in Group C (P<0.05) . Blood CKMB and CKII concentration increased after the operation in both groups (P<0.01)without statistic difference in the increments between groups (P>0.05) . HR increased at t₃, t₄ and t₅ (P<0.05) while MAP decreased only at t₂ CP<0.05 ) in both groups, with no significant difference between groups at each time point. CVP increased significantly after CPB in Group C (P<0.05) , and it did not change significantly in Group N CP>0.05) , also with no statistic difference between groups at each time point. LVSWI at t₂ t₃, t₄ and t₅ were lower than that at t₁ in Group C (P<0.05) , so was LVSWI at t₂ and t₅ in Group N (P<0.05) . RVSWI increased significantly after CPB in Group C (P<0.05 ) , while remained stable in Group N (P > 0.05). SI were lower at t₂, t₄ and t₅ than at t₁ in Group C (P<0.05 ) and lower only at t₂ than at t₁ in Group N (P<0.05) . LVSWI, RVSWI and SI at each time point showed no significant difference between groups (P>0.05) . SVR showed an uptrend after CPB in Group C while a downtrend in Group N, those at t₄ and t₅ were significantly higher in Group C than in Group N (P<0.05) . Three patients suffered new arrhythmia after CPB in Group C.Patients in both groups showed lower postoperative MMSE scores (P<0.05). However, those in Group N showed a smaller difference between postoperative and preoperative scores than in Group C (P<0.05) . Blood NSE concentration at T₂ and T₃ were higher than that at T-1 in both groups (P<0.05 ) , and the increment was smaller in group N (P<0.05) . Blood S100 β concentration at T₂ , T₃ and T₄ were higher than that at T₁ in Group C (P<0.01) , so was the blood S100 β concentration at T₄ in Group N (P<0.05) . Group N showed a smaller increment of blood S100 β concentration at T₂ and T₃ than Group C (P<0.05) .Conclusion Nicorandil, given orally as premedication, not only had a potential to stabilize circulation function after CPB , but also improved postoperative MMSE score and inhibited the increase of blood cTnI, NSE and S100 β concentration after CPB in patients undergoing on-pump CABG surgery, indicating both cardiac and cerebral protective effect.