ABSTRACT
Objective To evaluate the cardioprotection induced by combination of dexmedetomidine and limb ischemic preconditioning in the patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).Methods Eighty American Society of Anesthesiologists physical starus Ⅱ or Ⅲ patients of both sexes,aged 52-64 yr,weighing 51-78 kg,with New York Heart Association Ⅱ or Ⅲ,scheduled for elective CABG with CPB,were divided into 4 groups (n =20 each) using a random number table method:control group (group C),limb ischemic preconditioning group (group L),dexmedetomidine group (group D) and dexmedetomidine plus limb ischemic preconditioning group (group DL).Limb ischemic preconditioning was induced by 3 cycles of 5-min unilateral lower limb ischemia followed by 5-min reperfusion starting from 30 min before aortic clamping in L and DL groups.Dexmedetomidine was injected via the central vein in a loading dose of 1 μg/kg after induction of anesthesia,followed by an infusion of 0.4 μg · kg-1 · h-1 until the end of operation in D and DL groups.Venous blood samples were obtained immediately before aortic clamping,at the end of CPB and at the end of operation for determination of plasma concentrations of cardiac troponin Ⅰ (cTnI) by enzyme-linked immunosorbent assay.Myocardial tissues were obtained from the right auricle immediately before aortic clamping and at the end of CPB for determination of the expression of Bcl-2 and Bax (by immunohistochemistry) and apoptosis index (AI) (using TUNEL).The restoration of spontaneous heart beat was recorded.Bcl-2/Bax ratio was calculated.Results Compared with group C,the plasma cTnI concentrations were significantly decreased,the Bcl-2 expression was up-regulated,the Bcl-2/Bax ratio was increased,Bax expression was down-regulated,and AI was decreased in the other three groups (P＜0.05).Compared with L and D groups,the plasma cT-nI concentrations were significantly decreased,the Bcl-2 expression was up-regulated,the Bcl-2/Bax ratio was increased,Bax expression was down-regulated,and AI was decreased in group DL (P＜0.05).The rate of restoration of spontaneous heart beat was significantly increased in group DL as compared with the other three groups (P＜0.05).Conclusion Combination of dexmedetomidine and limb ischemic preconditioning can mitigate myocardial injury,it provides better efficacy than either alone,and the mechanism is related to inhibiting cell apoptosis in the patients undergoing CABG with CPB.
ABSTRACT
Objective To investigate the effect of intrathecal dexmedetomidine pretreatment on my-ocardial ischemia-reperfusion (I∕R) injury in rats. Methods Forty-five adult Sprague-Dawley rats of both sexes, weighing 200-250 g, in which intrathecal catheters were successfully placed without complications, were divided into 3 groups (n= 15 each) using a random number table: sham operation group (group S), group I∕R and intrathecal dexmedetomidine pretreatment group ( group DEX). Myocardial I∕R injury was produced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion. Dexmedetomidine 1 μg∕kg (diluted to 10 μl in normal saline) was intrathecally injec-ted at 30 min before ischemia in group DEX. The equal volume of normal saline was given in group I∕R. Blood samples were collected from the cardiac apex at the end of reperfusion for measurement of plasma nor-epinephrine (NE) and cardiac troponin I ( cTnI) concentrations. Then all the rats were sacrificed, and myocardial tissues were obtained for determination of myocardical infarct size, and the spinal cord was isola-ted to detect the expression of c-fos in the spinal dorsal horn by Western blot. Results Compared with group S, the myocardical infarct size, plasma NE and cTnI concentrations were significnatly increased, and the expression of c-fos in the spinal dorsal horn was up-regulated in I∕R and DEX groups (P<0. 05). Compared with group I∕R, the myocardical infarct size, plasma NE and cTnI concentrations were signific-natly decreased, and the expression of c-fos in the spinal dorsal horn was down-regulated in group DEX (P<0. 05). Conclusion Intrathecal dexmedetomidine pretreatment can reduce myocardial I∕R injury in rats, and the mechanims may be related to decreasing plasma NE levels and inhibiting c-fos expression in the spinal dorsal horn.