Aim To study the effect of Bay k8644 on cardiac function with the model of myocardial ischemia-reperfusion injury(MIRI)in Rats.Methods Rat MIRI was induced by occluding the left anterior descending coronary artery for 40 min followed by 90 min reperfusion.Eighteen rats were divided randomly into 3 groups: saline,Bay k8644 and 0.1% dimethyl sulfoxide(DMSO)intravenously injected 30 min after ischemia.Heart functions were assessed before ischemia and 5,20 and 40 min after initiation of ischemia and 5,30,60 and 90 min after reperfusion,by measuring heart rate(HR),the left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP) and ?dp/dt_(max).Results After ischemia,LVSP and +dp/dt_(max) decreased(P

BACKGROUND: KATP channel regulates the response of cells to hypoxia and ischemia, mediates and is involved in the protection for cells or tissue organs. Our previous research confirms that Shenfu injection has good protective effect on myocardial ischemia/reperfusion injury in rats. There have been no reports on whether this protective effect is related to KATP channel in WeiPu deriodical database, WanFang database and Medline database until October 2005.OBJECTIVE: To observe the protective effect of Shenfu injection on myocardial ischemia/reperfusion injury in rats, and analyze its correlation with KATP channel.DESIGN: Completely randomized grouping design, randomized controlled trial.SETTING: Department of Anesthesiology, Second Hospital Affiliated to Dalian Medical University; Department of Anesthesiology, Second Hospital Affiliated to Chongqing Medical University.MATERIALS: Twenty-four adult SD rats of clean grade, of either gender, weighing 240 to 320 g, were employed in this trial. Shenfu injection (Sanjiu Medical & Pharmaceutical, Co., Ltd., Batch No. 031002) and glibenclamide (National Institute for the Control of Pharmaceutical and Biological Products) were employed.METHODS: This trial was carried out in the Laboratory of Anesthesiology, Second Hospital Affiliated to Chongqing Medical University from April to December 2004. Myocardial ischemia/reperfusion injury models were employed. Twenty-four rats were randomized into 4 groups, with 6 in each group: sham-operation group [putting through thread, but without ligation of left anterior descending coronary artery, 8 mL/kg normal saline, intravenous injection (i.v.)], ischemia/reperfusion group (8 mL/kg normal saline, i.v.), Shenfu injection group (8 mL/kg Shenfu injection, i.v.) and Shenfu injection + glibenclamide group (0.33 mg/kg glibenclamide and 8 mL/kg Shenfu injection, i.v.). Administration in each group was conducted 15 minutes before ligation except for that in sham-operation group (immediately after putting through thread). About 6 mL blood was taken from cardiac apex. Left ventricular anterior wall was divided into 3 parts, and then which were used for homogenate, electron microscope observation and immunohistochemical detection separatety. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, expressions of tumor necrosis factor-α(TNF-α) and interleukin 6 (IL-6)and plasm cTnl level in myocardial tissue were detected. Ultra-structural changes of myocardial tissue were observed.MAIN OUTCOME MEASURES: SOD activity, MDA level, expressions of TNF-α and IL-6, plasm cTnI level and ultra-structural changes of myocardial tissue. RESULTS: All the 24 rats were involved in the result analysis, without deletion. ① Compared with sham-operation group,SOD activity in myocardial tissue in ischemia/reperfusion group was decreased, while the expressions of TNF-α and IL-6 were increased, with statistical difference (P ＜ 0.01). MDA level in the ischemia/reperfusion group was higher than that in the sham-operation group (P ＜ 0.01); Compared with ischemia/reperfusion group, SOD activity was increased, MDA level and expressions of TNF-α and IL-6 were all decreased in Shenfu injection group(P ＜ 0.01); There were no significant differences in above-mentioned indexes between Shenfu injection group and Shenfu injection + glibenclamide group (P ＞0.05). ②Compared with sham-operation group, the plasm cTnl level in the ischemia/reperfusion group and Shenfu injection+ glibenclamide group was significantly increased (P ＜ 0.01); Compared with ischemia/reperfusion group, plasm cTnl level in the Shenfu injection group was significantly decreased in Shenfu injection group (P ＜ 0.01); There were no signifi cant differences in plasm cTnl level between Shenfu injection group and Shenfu injection + glibenclamide group. ③ In the sham-operation group, the ultrastructure of myocardial cells was basically normal and mitochondrium swelled a little; In the ischemia/reperfusion group, karyolysis appeared, mitochondrium swelled obviously and considerable neutrophils infil trated; In the Shenfu injection group, myofilament of myocardial cells dissolved, mitochondrium swelled and nuclear mem brane was integrity; In the Shenfu injection + glibenclamide group, mitochondrium obviously swelled, myofilament present ed focus dissolving, sarcoplasmic reticulum expanded a little and allochromacy assembled in the edge of cells. CONCLUSION: Glibenclamide suppresses myocardial KATP channel, but does not eliminate the protective effect of Shenfu injection on myocardial ischemia/reperfusion injury. KTAP channel does not play an important role in the protection of Shenfu injection for myocardial ischemia/reperfusion injury.

BACKGROUND: It has been confirmed that Shenfu parenteral injection can ameliorate and treat various shocks, heart failure, myocardial ischemia and supraventricular/ventricular arrhythmia, and it also has a good protective effect on myocardial ischemia/reperfusion injury in rats.OBJECTIVE: To observe the effects of Shenfu parenteral injection on the protein expressions of myocardial apoptosis-related genes of Bcl-2, Bax and c-Fos in rats with acute ischemia/reperfusion injury.DESIGN: A complete randomized grouping design, controlled experiment.SETTING: Department of Anesthesiology, the Second Affiliated Hospital,Chongqing University of Medical Sciences.MATERIALS: The experiments were carried out in the Staff Room of Anesthesiology, the Second Affiliated Hospital, Chongqing University of Medical Sciences from April to December in 2004. Thirty-five healthy adult Wistar rats were provided by the experimental animaI center of Daping Hospital, Third Military Medical University of Chinese PLA. Shenfu parenteral injection was the TCM formula of Shenfu Tang, which is for recuperating depleted yang and rescuing the patient from collapse, and its main components are ginsenoside and aconitum alkaloid. It was the product of Yaan Sanjiu Pharmaceutical Co., Ltd., 10 mL/piece, the batch number was 030110.METHODS: In vivo models of myocardial ischemia/reperfusion injury were used. The 35 rats were divided into 5 groups according to the number of random number table, with 7 rats in each group: ① Sham-operated group: The rats were treated with only insertion of thread without ligation, followed by intravenous injection of saline (8 mL/kg), and then observed for 120 minutes. ② Shenfu parenteral injection 30-minute group: The rats were treated with intravenous injection of Shenfu parenteral injection (8 mL/kg) at 15 minutes before ligation, and then the left coronary artery anterior descending branch was ligated for 40 minutes and reperfused for 30 minutes. ③ Shenfu parenteral injection 120-minute group: The rats were reperfused for 120 minutes, and the others were the same as those in the Shenfu parenteral injection 30-minute group. ④ Saline 30-minute control group: The rats were treated with intravenous injection of saline (8 mL/kg) at 15 minutes before ligation, and then the left coronary artery anterior descending branch was ligated for 40 minutes and reperfused for 30 minutes. ⑤ Saline 120-minute control group: The rats were reperfused for 120 minutes, and the others were the same as those in the saline 30-minute control group. The expressions of Bcl-2, Bax and c-Fos proteins in myocardial tissues were detected with immunohistochemical method.MAIN OUTCOME MEASURES: The expressions of Bcl-2, Bax and cFos proteins in myocardial tissues of rats in each group were observed.RESULTS: All the 35 rats were involved in the analysis of results without deletion. ①As compared with the sham-operated group, the expressions of Bcl-2, Bax or c-Fos protein in myocardium were significantly increased(P ＜ 0.01), but the Bcl-2/Bax ratios were significantly decreased (P ＜0.01) in the saline 30 and 120-minute groups. ② As compared with corresponding saline groups, the expressions of Bcl-2 protein in the Shenfu parenteral injection 30 and 120-minute groups were significantly increased (P ＜ 0.01), the expressions of Bax and c-Fos proteins were remarkably decreased (P ＜ 0.01), and the Bcl-2/Bax ratios were significantly increased (P ＜ 0.01).CONCLUSION: Protective effect of Shenfu parenteral injection on ischemia/reperfusion myocardium may be correlated with its promotion of Bcl-2 protein expression, restrain to Bax and c-Fos protein expressions, and increase of Bcl-2/Bax ratio, and it restrains the apoptosis of myocardial cells.