| Background and objective:As one of important measures of perioperative blood protection,controlled hypotension has been widely used in clinic.However,intraoperative hypotensive anesthesia may lead to cerebral hypoperfusion and subsequent cerebral ischemic damages such as delayed recovery,postoperative delirium,postoperative cognitive dysfunction and stroke.Stroke is a serious complication with an incidence of between 0.1%and 0.8%in patients undergoing noncardiovascular surgery,and its risk is closely associated with hypotension and its duration,leading to an eight-fold increase in mortality after surgery.Therefore,it is very important to maintain the ability of cerebral perfusion and oxygenation during changes of systemic perfusion pressure under controlled hypotension.In the past,transcranial Doppler ultrasound or jugular bulb venous oxygen saturation was mainly used to monitor the overall cerebral perfusion under intraoperative controlled hypotension,and occurrence of obvious cerebral ischemia and hypoxia is not clear under a specific degree of hypotension.Compared with the overall cerebral perfusion,microcirculation perfusion is a sensitive index reflecting organ perfusion,which is helpful for detecting potential ischemia and hypoxia early.In this study,we use female Landrace pigs to establish a controlled hypotension model,by simulating clinical environment,microcirculation perfusion monitoring instrument-Oxygen to see(O2C)was used to monitor regional cerebral tissue blood flow and oxygenation under specific hypotension of commonly used antihypertensive drugs,aiming at finding potential cerebral ischemia and hypoxia,as well as providing suggestions for antihypertensive drugs in clinical application.Methods:Eighteen healthy female Landrace pigs were included in the study on controlled hypotension of sodium nitroprusside,nitroglycerin and nicardipine,respectively(n=6).Sodium nitroprusside,nitroglycerin,nicardipine were used for controlled hypotension(20%,30%,50%lower than the baseline of mean arterial pressure(MAP),corresponding to mild,moderate and severe hypotension,respectively)under sevoflurane anesthesia(1-1.5 minimum alveolar concentration(MAC)),respectively.O2C,a monitoring instrument,was used to measure regional cerebral tissue blood flow(rCBF)and regional cerebral tissue oxygen saturation(rSO2)in the forehead of pigs.rCBF,rSO2,regional cerebral tissue hemoglobin(rHb),heart rate(HR),peripheral blood oxygen saturation(SpO2)and cerebral hypoxia events(rSO2 decreased by 20%or more from the baseline value for at least 15 seconds)of three different antihypertensive drugs were recorded at different time points(5 min,10 min,15 min after starting hypotension)under different MAP.Part I:Effects of controlled hypotension with sodium nitroprusside on regional cerebral tissue blood flow and oxygenation in pigsResults:rCBF was moderately correlated with MAP(r1=0.793)and significantly correlated with rSO2(r2=0.843)during controlled hypotension of sodium nitroprusside.In addition,rSO2 also had a significant correlation with MAP(r3=0.823).rSO2 had a linear correlation with rHb,MAP and rCBF(R2=0.853,P<0.05),respectively.At 5min,10min,15min during mild hypotension,rCBF increased by 6.5%(P<0.05),7.3%(P<0.05)and 8.7%(P<0.05)from baseline(192(169,215)arbitrary unit(AU))on average,respectively;rSO2 increased by 2.4%(P<0.05),2.5%(P<0.05)and 2.5%(P<0.05)from baseline(69(66,72)%)on average,respectively.At different time points during moderate hypotension,rCBF decreased by 2.4%(P<0.05),0.3(P>0.05)and 0.1(P>0.05)from baseline on average,respectively;rSO2 decreased by 6.3%(P<0.05),5.6%(P<0.05)and 5.3%(P<0.05)from baseline on average,respectively.At different time points during severe hypotension,rCBF decreased by 6.2%(P<0.05),6.7%(P<0.05)and 9.7%(P<0.05)from baseline on average,respectively;rSO2 decreased by 11.3%(P<0.05),12.4%(P<0.05)and 12.7%(P<0.05)from baseline on average,respectively.Compared with baseline,at different time points after drug withdrawal,rCBF decreased by 8.7%(P<0.05),8.8%(P<0.05)and 7.9%(P<0.05)on average,respectively;rSO2 decreased by 3.5%(P<0.05),3.6%(P<0.05)and 1.9%(P<0.05)on average,respectively.There was no cerebral hypoxia event during mild to severe hypotension of sodium nitroprusside.When MAP recovered to near baseline,rCBF and rSO2 increased by 3.7%(P<0.05)and 1.4%(P<0.05)from baseline,respectively.At different time points during mild hypotension,HR decreased by 1.0%(P<0.05),1.2%(P<0.05)and 1.3%(P<0.05)on average from baseline(80(74,87.25)bpm),respectively,but there was no significant difference in SpO2 from baseline(99(98,100)%).At different time points during moderate hypotension,HR and SpO2 decreased by 2.4%(P<0.05),2.8%(P<0.05),2.8%(P<0.05)and 1.1%(P<0.05),1.1%(P<0.05),1.1%(P<0.05)from baseline on average,respectively.At different time points during severe hypotension,HR and SpO2 decreased by 2.0%(P<0.05),1.7%(P>0.05),1.5%(P>0.05)and 0.7%(P<0.05),0.6%(P<0.05),2.1%(P<0.05)from baseline on average,respectively.At different time points after drug withdrawal,HR decreased by 2.0%(P<0.05),1.8%(P<0.05)and 2.3%(P<0.05)compared with baseline,but there was no significant difference in SpO2 from baseline.Part Ⅱ:Effects of nitroglycerin-induced hypotension on regional cerebral tissue blood flow and oxygenation in pigsResults:Strong correlation between changes in MAP and rSO2 was observed(r4=0.814)during controlled hypotension of nitroglycerin;and rCBF had a moderate correlation with MAP(r5=0.516)and was weakly correlated with rSO2(r6=0.478).rSO2 had a linear correlation with MAP,HR and rCBF(R2=0.642,P<0.05),respectively.Due to the obvious tolerance of it during hypotension,nitroglycerin could steadily reduce MAP by 20%and 30%.Only two experiments reduced MAP by 50%.At 5min,10min,15min during mild hypotension,rCBF decreased by 3.8%(P<0.05),3.8%(P<0.05)and 3.9%(P<0.05)from baseline(160.5(149.5,173.5)AU)on average,respectively;rSO2 decreased by 1.9%(P<0.05),2.2(P<0.05)and 3.3(P<0.05)from baseline(73.5(71,78)%)on average,respectively.At different time points during moderate hypotension,compared with baseline,rCBF decreased by 9.8%(P<0.05),8.4%(P<0.05)and 7.8%(P<0.05)on average,respectively;rSO2 decreased by 9.4%(P<0.05),10.7%(P<0.05)and 10.6%(P<0.05)on average,respectively.At different time points after drug withdrawal,rCBF declined by an average of 2.3%(P>0.05),2.7%(P<0.05)and 0.5%(P>0.05)from baseline,respectively;rSO2 decreased by an average of 9.6%(P<0.05),9.2%(P<0.05)and 7.4%(P<0.05)from baseline,respectively.During hypotension,cerebral hypoxia events occurred when MAP reduced by 50%in only one experiment.When MAP returned to baseline,rCBF increased by 4.4%(P<0.05)compared with baseline.However,rSO2 decreased by 6.3%(P<0.05)from baseline.At different time points during mild hypotension,HR decreased by 2.6%(P<0.05),2.9%(P<0.05)and 3.8%(P<0.05)on average from baseline(76.5(60,80)bpm),respectively,but there was no significant difference in SpO2 from baseline(98.5(97,100)%).At different time points during moderate hypotension,HR and SpO2 declined by an average of 5.4%(P<0.05),5.7%(P<0.05),5.2%(P<0.05)and 0.8%(P<0.05),0.7%(P<0.05),0.9%(P<0.05)from baseline,respectively.At different time points after drug withdrawal,compared with baseline,SpO2 decreased by 1.0%(P<0.05),0.9%(P<0.05)and 0.3%(P<0.05),respectively,but there was no significant difference in HR.Part Ⅲ:Effects of nicardipine-induced hypotension on regional cerebral tissue blood flow and oxygenation in pigsResults:rCBF was moderately correlated with rSO2(r7=0.671),while MAP was highly correlated with rCBF and rSO2(r8=0.800 andr9=0.860,respectively)during controlled hypotension of nicardipine.rSO2 had a linear correlation with MAP and rHb(R2=0.773,P<0.05),respectively.At different time points during mild hypotension,compared with baseline((187±10)AU),rCBF decreased by 5.6%(P<0.001),6.3%(p<0.001)and 6.8%(P<0.001)on average,respectively;rSO2 decreased by 1.7%(P<0.001),2.4%(P<0.001)and 2.7%(P<0.001)on average from baseline(70.5(68,77.3)%),respectively.At different time points during moderate hypotension,compared with baseline,rCBF decreased by 11.0%(P<0.001),11.6%(P<0.001)and 12.4%(P<0.001)on average,respectively;rSO2 decreased by 6.3%(P<0.001),6.3%(P<0.001)and 6.9%(P<0.001)on average,respectively.At different time points during severe hypotension,rCBF decreased by 18.4%(P<0.001),20.2%(P<0.001)and 19.7%(P<0.001)from baseline on average,respectively;rSO2 decreased by 15.1%(P<0.001),16.2%(P<0.001)and 15.8%(P<0.001)from baseline on average,respectively.At different time points after drug withdrawal,compared with baseline,rCBF decreased by 18.5%(P<0.001),16.5%(P<0.001)and 13.0%(P<0.001)on average,respectively;rSO2 decreased by 15.8%(P<0.001),15.2%(P<0.001)and 13.0%{P<0.001)on average,respectively.During hypotension,there were only two experiments in which cerebral hypoxia events occurred when MAP fell by 50%.When MAP recovered to near baseline after drug withdrawal,both rCBF and rSO2 did not restore,which decreased by 2.7%(P<0.05)and 4.3%(P<0.05)from baseline,respectively.At different time points during mild hypotension,HR decreased by 1.6%(P<0.05),2.7%(P<0.05)and 2.9%(P<0.05)from baseline(74.5(60,79)bpm)on average,respectively;SpO2 decreased by 0.5%(P<0.05),0.5%(P<0.05)and 0.6%(P<0.05)from baseline(100(99,100)%)on average,respectively.At different time points during moderate hypotension,HR and SpO2 decreased by 5.3%(P<0.05),6.7%(P<0.05),8.7%(P<0.05)and 1.5%(P<0.05),1.5%(P<0.05),1.6%(P<0.05)from baseline on average,respectively.At different time points during severe hypotension,HR and SpO2 decreased by 9.6%(P<0.05),9.3%(P<0.05),9.7%(P<0.05)and 2.3%(P<0.05),2.6%(P<0.05),2.8%(P<0.05)from baseline on average,respectively.At different time points after drug withdrawal,HR and SpO2 decreased by 10.9%(P<0.05),10.1%(P<0.05),9.3%(P<0.05)and 2.4%(P<0.05),2.1%(P<0.05),1.6%(P<0.05)from baseline on average,respectively.During mild hypotension,sodium nitroprusside(7.4%)significantly increased rCBF(P<0.05),but nitroglycerin(-3.9%)and nicardipine(-6.3%)significantly decreased rCBF(P<0.05);sodium nitroprusside(2.5%)also increased rSO2 significantly(P<0.05),but nitroglycerin(-2.5%)and nicardipine(-2.2%)decreased rSO2 significantly(P<0.05)and there was no significant difference in rCBF and rSO2 between nitroglycerin and nicardipine.During moderate hypotension,compared with sodium nitroprusside(-0.8%),nicardipine(-11.8%)and nitroglycerin(-8.7%)significantly decreased rCBF(P<0.05),and nicardipine decreased rCBF more than nitroglycerin(P<0.05);compared with sodium nitroprusside(-5.8%)and nicardipine(-6.5%),nitroglycerin(-10.0%)decreased rSO2 more significantly(P<0.05),but there was no significant difference in rSO2 between sodium nitroprusside and nicardipine.During severe hypotension,nicardipine(-19.5%)significantly decreased rCBF compared with sodium nitroprusside(-7.6%)(P<0.05);compared with sodium nitroprusside(-12.1%),nicardipine(15.7%)significantly decreased rSO2(P<0.05).Within 15min after drug withdrawal,sodium nitroprusside(8.5%)increased rCBE significantly(P<0.05)compared with nicardipine(16.1%).At the same time,sodium nitroprusside(3.0%)also increased rSO2 significantly(P<0.05)compared with nicardipine(-14.7%);while nitroglycerin decreased rCBF(-1.8%)and rSO2(-8.7%)(P<0.05).Conclusions:1.During mild hypotension,sodium nitroprusside increases rCBF and rSO2;nitroglycerin and nicardipine decrease rCBF and rSO2,and their effects on rSO2 are similar.2.During moderate hypotension,the degree of rCBF reduction is nicardipine>nitroglycerin>sodium nitroprusside.The degree of rSO2 reduction is nitroglycerin>sodium nitroprusside and nicardipine,and the effects of sodium nitroprusside and nicardipine on rSO2 are similar.3.During severe hypotension,nicardipine decreases rCBF and rSO2 more significantly than sodium nitroprusside and has a greater risk of cerebral ischemia and hypoxia during severe hypotension.4.After drug withdrawal,sodium nitroprusside rapidly recovers rCBF and rSO2,and their levels are higher than those before hypotension;rCBF and rSO2 remain significantly lower than pre-hypotension levels for a long time after withdrawal of nitroglycerin and nicardipine. |
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