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Objective To investigate the effects of propofol and sevoflurane on adriamycin chemotherapy-induced myocardial damage in rats.Methods Twenty-four healthy male Wistar rats, aged 3 months, weighing 212-270 g, were randomly divided into 4 groups (n =6 each) using a random number table: control group (group C) , adriamycin group (group ADM) , adriamycin-propofol group (group ADM-Pro) , and adriamycin-sevoflurane group (group ADM-Sevo).The equal volume of normal saline was injected intraperitoneally in group C.In group ADM, adriamycin 2.5 mg/kg was injected intraperitoneally once every other day for 6 times (11 days in total).In group ADM-Pro, adriamycin 2.5 mg/kg was injected intraperitoneally once every other day for 6 times, and at 3 days after the last administration of adriamycin, propofol anesthesia was performed as follows : the total amount of propofol injected intraperitoneally was 200 mg/kg, the initial dose was 100 mg/kg, and 1 h later the remaining amount was added, and the duration of anesthesia was about 2 h.In group ADM-Sevo, adriamycin 2.5 mg/kg was injected intraperitoneally once every other day for 6 times, and at 3 days after the last administration of adriamycin, sevoflurane anesthesia was performed as follows: 1.5％-3.0％ sevoflurane was inhaled for 2 h.After the end of anesthesia, blood samples were collected for determination of serum cardiac troponin (cTnI) concentrations.Myocardial specimens were collected for detection of caspase-3 expression by immuno-histochemistry.Results Compared with group C, the serum cTnI concentration was significantly increased, and the caspase-3 expression was up-regulated in ADM, ADM-Pro and ADM-Sevo groups (P＜ 0.05).Compared with group ADM, the serum cTnI concentration was significantly decreased, and the caspase-3 expression was down-regulated in ADM-Pro and ADM-Sevo groups (P＜0.05).There was no significant difference in the parameters mentioned above between group ADM-Pro and group ADM-Sevo (P＞0.05).Conclusion Propofol and sevoflurane both can mitigate adriamycin chemotherapy-induced myocardial damage in rats, without significant difference in the efficacy.
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Objective To evaluate the effect of sevoflurane pretreatment on the inflammatory response during renal ischemia-reperfusion (I/R) in rats.Methods Thirty pathogen-free male Sprague-Dawley rats,aged 12-14 weeks,weighing 220-260 g,were randomized into 3 groups (n =10 each) using a random number table:sham operation group (group S),I/R group and sevoflurane pretreatment group (group SP).Renal I/R was induced by clamping the left renal pedicle for 45 min followed by reperfusion in I/R and SP groups.In group S inhalation of 3％ sevoflurane in O2 was started at 30 min before I/R and maintained throughout the experiment.Venous blood samples were taken at 3 h of reperfusion for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The animals were then sacrificed and the left kidneys were removed for microscopic examination and for measurement of the content of tumor necrosis factor-apha (TNF-α),interleukin-6 (IL-6) and intercellular cell adhesion molecule-1 (ICAM-1) in renal tissues (by ELISA).Results Compared with group S,the serum BUN and Cr concentrations,severity of necrosis of renal proximal convoluted tubules (0 =normal,4 =necrosis of whole segment of proximal convoluted tubules),and contents of TNF-α,IL-6 and ICAM-1 were significantly increased in I/R and SP groups (P ＜ 0.05).Compared with group I/R,the serum BUN and Cr concentrations,severity of necrosis of renal proximal convoluted tubules,and contents of TNF-α,IL-6 and ICAM-1 were significantly decreased in SP group (P ＜ 0.05).Conclusion Sevoflurane pretreatment can protect kidney against I/R injury by inhibiting the inflammatory responses in the renal tissues of rats.
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Objective To investigate the effects of preconditioning with different doses of levothyroxine sodium on myocardial ischemia-reperfusion (I/R) injury in immature rats. Methods Forty-eight female immature Wistar rats, aged 35 days, weighing 120-140 g, were randomly allocated into 6 groups ( n = 8 each): control group (group C), I/R group, and preconditioning with levothyroxine sodium 10, 20, 40 and 80 μg/100 g groups (groups LS1-4 ) . The rats received levothyroxine sodium 10, 20, 40 and 80 μg/100 g through a gastric tube every day for 7 days in groups LS1-4 , respectively. Venous blood samples were taken on 8th day for determination of serum thyroid hormone levels. The hearts were removed from the animals and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 37 ℃. The hearts were continuously perfused for 80 min in group C. After 30 min of equilibration, the isolated hearts were subjected to 20 min of ischemia followed by 30 min of reperfusion in I/R and LS1-4 groups. HR, SP and ± dp/dtmax were recorded at 20 min of perfusion and 30 min of reperfusion. The recovery rates of HR, SP and ± dp/dtmax were calculated at 30 min of reperfusion. The coronary effluent was collected at 10 min of perfusion and 15 min of reperfusion for determination of creatine kinase (CKMB) activity. The samples of ventricular myocardial tissues were taken at 30 min of reperfusion to detect the expression of heat shock protein 70 (HSP70), thyroid hormone receptor (TR) mRNA (TRa, , TRoj and TRft ) and myosin heavy chain (MHC) mRNA. Results Compared with group C, the recovery rates of HR, SP and. ± dp/dtmax were significantly decreased, the CK-MB activity was significantly increased, and MHCα mRNA expression was down-regulated in group I/R, the recovery rates of SP and ± dp/dtmax were significantly decreased, the CK-MB activity was significantly increased, and the expression of HSP70 and MHCα mRNA was up-regulated in groups LS1-4, and the serum thyroid hormone level was significantly increased and the expression of TRa, mRNA was up-regulated in groups LS2-4 ( P ＜ 0.05) . Compared with group I/R, the recovery rates of HR and ± dp/dtmax were significantly increased, the pression of HSP70 and MHCa mRNA was up-regulated, and the MHCJ3 mRNA expression was down-regulated in groups LS1-4 the CK-MB activity was significantly decreased in groups LS1-3, and the serum thyroid hormone level was significantly increased and the expression of TRα1, mRNA was up-regulated in groups LS2-4 ( P ＜ 0.05) . The serum thyroid hormone level increased gradually with the increase in the dose of levothyroxine sodium in groups LS1-4 ( P ＜ 0.05) . The CK-MB activity was significantly higher, while the HSP70 expression lower in groups LS3-4 than in groups LS1-2 (P ＜ 0.05). Conclusion Preconditioning with levothyroxine sodium 10 μg/100 g can alleviate the myocardial I/R injury in immature rats and does not lead to the increase in the level of thyroid hormone, and the up-regulation of HSP70 and MHCa mRNA expression may be involved in the mechanism.
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Objective To evaluate the protective effects of fentanyl postconditioning and remote limb ischemic postconditioning (RLIP) against myocardial ischemia-reperfusion (I/R) injury in rats. Methods Thirty-nine male SD rats aged 8 weeks weighing 250-350 g were randomly allocated into 5 groups: Ⅰ group sham operation (group S, n = 5); Ⅱ group I/R ( n = 7); Ⅲ group fentanyl postconditioning (group F, n= 9); Ⅳ group RLIP (group R, n = 9) and group Ⅴ fentanyl postconditioning + RLIP (group F-R, n = 9). The animals were anesthetized with intraperitoneal 3% pentobarbital 50 mg/kg, intubated and mechanically ventilated. Myocardial I/R was induced by occlusion of anterior desending branch of left coronary artery for 30 min followed by 180 min reperfusion. Fentanyl 30 μg/kg was injected iv at 15 min of myocardial ischemia in group F and F-R In group R and F-R the animals underwent 10 min ischemia of bilateral hind limbs starting from 15 min of myocardial ischemia. HR and MAP were recorded at 5,60,120 and 180 min of reperfusion and rate-pressure product( RPP, HR × MAP) were calculated. At the end of 180 min reperfusion, arterial blood samples were obtained for measurement of the activities of plasma lactate dehydrogenase (LDH) and creatine kinase isoenzyme MB (CK-MB), and the concentration of serum cardiac troponin Ⅰ (cTnI). The animals were then sacrificed. The infarct size was evaluated by double staining with Evans blue and triphenyl tetrazolium chloride. Results Myocardial I/R significantly increased plasma LDH and CK-MB activities and serum cTnI concentration and decreased HR,MAP and RPP as compared with group S.Fentanyl postconditioning and RLIP both decreased plasma CK-MB activity, serum cTnI concentration and infarct size and increased HR, MAP and RPP in group F, R and F-R as compared with group I/R. Plasma CK-MB activity,serum cTnI concentration and RPP were significantly lower and infarct size was smaller in group F-R than in group F. The infarct size was significantly smaller and MAP and RPP were higher in group F-R than in group R.Conclusion Fentanyl postconditioning can provide a myocardial protection against I/R injury. Myocardial protection is enhanced by combination of fentanyl postconditioning and RLIP.
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Objective To evaluate the preventive efficacy of oral small-dose thyroid hormone tablet premedication for a short time on euthyroid sick syndrome (ESS) in children undergoing open heart surgery under cardiopulmonary bypass (CPB) .Methods Forty ASA Ⅰ or Ⅱ children aged 3-12 yr, weighing 10-30 kg, scheduled for elective congenital heart disease surgery under CPB, were randomly allocated into 2 groups ( n = 20 each):placebo group (group P) and thyroid hormone tablet group (group T). Group T received oral thyroid hormone tablets 0.4 mg/kg every day for 4 consecutive days before surgery, while group C were given placebo. CPB was routinely established, and mild hypothermia, moderate hemodilution and high flow perfusion were adopted. Blood samples were taken from radial veins before administration (baseline) and on 1st, 2nd and 4th day after surgery to detect the serum concentrations of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH).SP, DP and HR were recorded before administration, immediately after surgery, and on 1st and 2nd day after surgery. The endotracheal extubation time, length of ICU stay, application of positive inotropic agents and occurrence of ESS were recorded. Results No significant difference was found in hemodynamic parameters, endotracheal extubation time and length of ICU stay between the two groups ( P ＞ 0.05). As compared with the baseline values,the serum T3 levels on 1st, 2nd and 4th day after surgery, and the serum TSH levels on 1 st day after surgery were significantly decreased in the two groups, and the serum T4 levels were significantly decreased on 1 st day after surgery in group P ( P ＜ 0.05). The serum levels of T3 and T4 were significantly higher, the severity of postoperative ESS and the number of positive inotropic agent administration were significantly lower in group T than in group P (P ＜ 0.05 ). Conclusion Although oral small-dose thyroid hormone tablet premedication for 4 days (0.4 mg/kg per day) can reduce the severity of postoperative ESS, but it can not prevent the occurrence of ESS in children undergoing open heart surgery under CPB.