Effect Of Carveclilol On Cardiac Function And Toll-like Receptor4Expression After AMI In Rats

Objective: Left ventricular remodeling and infarct size secondary to myocardialinfarction is still a major determinant of morbidity and mortality.Toll-like receptor4serves as pattern recognition receptor of innate immune system,which is also involvedin LV remodeling and infarct size after MI.carvedilol,a unique blocker withnon-selective-blockade,a1-blockade and antioxidant effects,is greatly used forischemic heart disease owing to its protection cardiac function,reducing infarct size,inhibiting LV remodeling and inflammation cytokines expression.The present study wehypothesized that carvedilol protects against MI associated with suppressing tlr4expression.Methods: All rats were randomized to the following groups before surgury:(1)sham-operated (n=10)groups,(2)AMI controls(n=10),(3)low dose (n=10;2mg/kg perday),(4)middle dose(n=10;10mg/kg per day),(5)high dose(n=10;30mg/kg per day)carvedilol, and(6)PDTC(n=10;150mg/kg per day)groups.Sham groups and AMIcontrols were given vehicle,and carvedilol groups and PDTC groups received differentdose carvedilol and PDTC by direct gastric gavage for7days. In the fourth day,wedistinguished differnent groups by ligation LAD to make animals model succeed.Results:(1) Infarct size was similar among infracted groups(P>0.05). Left ventricularweight／body weight ratio was also similar in all groups(P>0.05).Non-infarctedmyocardial collagen volume fraction was increased compared to sham group(P<0.05),but no differences in MI and treatment groups(P>0.05).(2) Compared withsham group,model group LVSP,positive and negative LV dP/dt were reduced,LVEDPwas increased(P<0.05).Compared with model group,carvedilol and PDTC reduced LV end-diastolic pressure(P<0.05),carvedilol also increased LV end-systolicpressure(P<0.05).low dose carvedilol improves Positive and negative LV dP/dt afterMI(P<0.05).High dose Carvedilol group also reduced heart rate compared to shamgroup(P<0.05).(3) Myocardial TLR4,-arrestin2and NF-κ B were increased in MIgroup(P<0.05).Compared to MI group,low dose carvedilol reduced myocardialTLR4protein expression and increased myocardial-arrestin2protein levels(P<0.05),whileNF-κ B was no significant differences between MI and carvedilol groups.Conclusion: Carvedilol can improves cardiac function after MI,probably throughinhibit of myocardial TLR4expression...