ABSTRACT
OBJECTIVE： To investigate the effects of ligustrazine structural modification product Liguzinediol on hemodynamics in chronic heart failure （CHF） model rats induced by adriamycin. METHODS： SD rats were given intraperitoneal injection of adriamycin （2 mg/kg） to induce CHF model. Model rats were randomly divided into normal saline group， positive control group （Deacetyl tricyanidin injection， 0.022 5 mg/kg） and Liguzinediol low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg）， with 8 rats in each group. Other 8 normal rats were selected as blank control group （normal saline）. Each group was given relevant medicine intravenously. The left ventricular systolic pressure （LVSP）， maximal rate of rise or drop of left ventricular （±dp/dtmax）， systolic pressure （SP）， diastolic pressure （DP）， heart rate （HR） and other hemodynamic indexes were recorded by multichannel physiological recorder at 1， 5， 10， 20， 40， 60， 90， 120 min after medication. RESULTS： Compared with blank control group， LVSP， +dp/dtmax， │－dp/dtmax│， SP， HR and DP at 120 min after medication of normal saline group were decreased significantly （P＜0.05）. Compared with normal saline group， LVSP at 5-60 min after medication， +dp/dtmax at 40-90 min after medication， SP at 10-40 min after medication were increased significantly in Liguzinediol low-dose group （P＜0.05 or P＜0.01）. LVSP at 5-90 min after medication， SP at 10-60 min after medication， DP at 10-60 min （except for 20 min） after medication were increased significantly in Liguzinediol medium-dose group （P＜0.05 or P＜0.01）. LVSP at 1-120 min after medication， +dp/dtmax at 5-90 min after medication， │－dp/dtmax│， and SP at 5-60 min after medication， DP at 40-60 min after medication were increased significantly in Liguzinediol high-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Single intravenous injection of Liguzinediol can significantly enhance ventricular systolic function of CHF model rats so as to control or relieve CHF.
ABSTRACT
OBJECTIVE To explore kinetic features and its underlying mechanism of the positive inotropic effect of liguzinediol(LZDO)in rats. METHODS ①An In vivo study was made to record the effect of LZDO 20 mg · kg-1 injected for 30 consecutive min from the left external jugular vein on pressure-volume relationships. ②Ex vivo study was used to record the antagonistic effect of LZDO on reduced contractility induced by caffeine. Caffeine and LZDO were perfused as follows:normal perfusion solution, caffeine 0.5 mmol · L-1,and then caffeine 0.5 mmol · L-1+LZDO 100 μmol · L-1. ③ Ca2+ transient from cardiomyocyte sarcoplasmic reticulum (SR) was measured to analyze the effect of LZDO on Ca2 +release blocked by thapsigargin. Thapsigargin and LZDO were perfused as follows:normal perfusion solution,thapsigargin 2 μmol · L-1,and then thapsigargin 2 μmol · L-1+LZDO 100 μmol · L-1.④The SR vesicles were prepared and the effect of LZDO(1,10 and 100μmol·L-1)on sarcoplasmic reticulum Ca2+ATPase(SERCA2a)activity was determined according to the ultramicro-Ca2+-ATP enzyme kit. RESULTS ① LZDO 20 mg · kg- 1 significantly reduced the end-systolic volume (Ves) and enhanced the end-systolic pressure (Pes),stroke volume (SV),ejection fraction (EF),cardiac output(CO),peak rate of rise of left ventricular pressure(+dp/dtmax)and stroke work(SW)(P<0.05). However,LZDO 20 mg · kg-1 did not significantly change the heart rate(HR )or the end-diastolic volume (Ved). ② Caffeine 0.5 mmol · L- 1 significantly enhanced HR,left ventricular developed pressure (LVDP ),and+dp∶dtmax at 5 min after caffeine and decreased at 30 min. However,LZDO 100μmol·L-1 restored the reduced HR,LVDP,and+dp/dtmax induced by caffeine at 30 min(P<0.05).③Thapsigargin 2μmol·L-1 significantly reduced the SR Ca2+transient from perfusion solution group(100±5)%to(51± 5)%(P<0.05) and LZDO 100 μmol · L-1 failed to restore the decreased Ca2+ transient〔(49 ± 4)%〕. Normalized Ca2+transients were reduced by thapsigargin 2μmol·L-1 and thapsigargin 2μmol·L-1+LZDO 100 μmol · L-1. ④ LZDO(10 and 100 μmol · L-1)significantly increased the activities of SERCA2a in perfusion solution group 0.98±0.10 to 1.17±0.20 and (1.43±0.09)μmol Pi·g-1·h-1,respectively(P<0.05). CONCLUSION LZDO can enhance SR Ca2+ gradient by activating the SERCA2a and might be developed to serve as a potential positive inotropic agent in clinical settings.