RESUMO
OBJECTIVE To explore the effects of alfentanil （ALF） on myocardial fibrosis in rats with acute myocardial infarction （AMI） by regulating sphingosine kinase 1 （SphK1）/sphingosine 1-phosphate （S1P） signaling pathway. METHODS Male SD rats were collected to construct AMI model by the ligation of anterior descending branch of left coronary artery. The successfully modeled rats were randomly divided into AMI model group （Model group）， ALF low-dose group （ALF-L group， 0.25 mg/kg ALF）， ALF high-dose group （ALF-H group， 0.5 mg/kg ALF）， high dose of ALF+SphK1 activator group （ALF-H+K6PC-5 group， 0.5 mg/kg ALF+1 μg/g K6PC-5）. At the same time， a sham operation group （Sham group） was set up to perform only chest opening/closing operations without ligating the anterior descending branch of left coronary artery， with 15 rats in each group. Rats in each drug group were intraperitoneally injected with the corresponding drug solution， once a day， for 4 consecutive weeks. Twelve hours after the last medication， cardiac function indicators [left ventricular systolic pressure （LVSP）， left ventricular ejection fraction （LVEF）， left ventricular systolic diameter （LVSD）， left ventricular fractional shortening （LVFS）] of rats were detected in each group； the condition of myocardial infarction， pathological changes in myocardial tissue， and degree of fibrosis were observed； serum levels of brain natriuretic peptide （BNP） and cardiac troponin Ⅰ （cTnⅠ） in rats were detected. The protein expressions of collagen Ⅰ ， collagen Ⅲ ， matrix metalloproteinase-2 （MMP-2）， SphK1 and S1P were alsodetected in the myocardial tissue of rats. RESULTS Compared with the Sham group， the arrangement of myocardial cells in the Model group was disordered， with a large number of inflammatory cells infiltrating. The levels of LVSP， LVFS and LVEF in the Model group were significantly reduced （P＜0.05）； LVSD level， myocardial infarction area， collagen volume fraction， serum levels of BNP and cTnⅠ， the protein expressions of collagen Ⅰ， collagen Ⅲ， MMP-2， SphK1 and S1P in myocardial tissue were significantly increased or enlarged （P＜0.05）. Compared with the Model group， the pathological changes and degree of fibrosis in the myocardial tissue of rats in each dose group of ALF were improved or relieved， while the quantitative indicators of rats in the ALF-H group were significantly improved and significantly better than those in ALF-L group （P＜0.05）. K6PC-5 could significantly reverse the improvement effect of high-dose ALF on the above quantitative indicators in rats （P＜0.05）. CONCLUSIONS ALF can reduce myocardial fibrosis and improve cardiac function in AMI rats， and the effect may be related to the inhibition of the SphK1/S1P signaling pathway.
RESUMO
Objective To investigate the clinical effect of remimazolam combined with remifentanil in patients undergoing laryngoscope vocal cord surgery under general anesthesia.Methods A total of 180 patients undergoing laryngoscope vocal cord surgery under general anesthesia from January to August 2022,77 males and 103 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ were select-ed.The patients were divided into four groups using a random number table method:propofol group(group C),remimazolam 1.0 mg·kg-1·h-1 group(group R1),remimazolam 1.5 mg·kg-1·h-1 group(group R2),and remimazolam 2.0 mg·kg-1·h-1 group(group R3),45 patients in each group.Group C main-tained by intravenous infusion of propofol 5 mg·kg-1·h-1,groups R1,R2,and R3 were maintained by intravenous infusion of remimazolam 1.0,1.5,and 2.0 mg·kg-1·h-1,respectively.All patients were combined with remifentanil 0.2 μg·kg-1·min-1.HR,MAP,and BIS were recorded before anesthesia in-duction(T1),immediately after laryngoscope insertion(T2),immediately at the end of anesthesia mainte-nance(T3),and at tracheal extubation(T4).The onset time of sedation,awakening time,sedation-agita-tion score at extubation and Ramsay score 5 minutes after extubation were recorded.The intraoperative use of ephedrine and nitroglycerin were recorded.The number of injection pain and remedy sedations were recor-ded,the occurrence of adverse reactions such as nausea and vomiting,respiratory depression within 1 hour after extubation,and intraoperative awareness were recorded.Results Compared with group C,MAP at T3,BIS at T2 and T3 were significantly increased,MAP at T4 was significantly decreased,the onset time of sedation was significantly prolonged,the use of ephedrine and the incidence of injection pain were signifi-cantly decreased in group R1(P＜0.05),HR and MAP were significantly decreased at T2 and T4,MAP was significantly increased at T3,the onset time of sedation,awakening time,extubation time were signifi-cantly prolonged,the use of ephedrine and the incidence of injection pain were significantly reduced in group R2(P＜0.05),HR and MAP were significantly decreased at T2 and T4,the onset time of sedation,awakening time,extubation time were significantly prolonged,Ramsay score was significantly increased in group R3(P＜0.05).Compared with group R1,HR and MAP were significantly decreased at T2 and T4,BIS was significantly decreased at T2 and T3,the awakening time and extubation time were significantly pro-longed in group R2(P＜0.05),HR at T2 and T4,MAP at T2-T4,BIS at T2 and T3 were significantly de-creased,the awakening time and extubation time were significantly prolonged,Ramsay score was significant-ly increased in group R3(P＜0.05).Compared with group R2,MAP at T3 was significantly decreased and Ramsay score was significantly increased in group R3(P＜0.05).There were no significantly differences between the rates of nitroglycerin usage,rescue sedation,nausea and vomiting,and respiratory depression in the four groups.Conclusion Remimazolam can be safely used for anesthesia induction and maintenance in laryngoscope vocal cord surgery.The maintenance of remimazolam 1.5 mg·kg-1·h-1 combined with remifentanil can better maintain the hemodynamics stability during the surgery than remimazolam 1.0 and 2.0 mg·kg-1·h-1.