The Establishment Of A Rabbit Model Of Sick Sinus Syndrome Combined With Yang Deficiency And Blood-stasis Syndrome And The Intervention Effect Of Qiangxin Fumai Granule

Background:Sick Sinus Syndrome(SSS) is a kind of clinically common and refractory cardiovascular disease, the Chinese Medicine Syndrome Types of which is mostly classified into yang deficiency and blood-stasis syndrome. Qiangxin Fumai Granule(QFG) is a empirical formula of famous TCM veteran doctor Liu Zhi-ming on treating SSS classified as yang-deficiency and blood-stasis syndrome.It had been used in clinic for many years and proved with identified remarkable effects.In our previous experimental research we had demonstrated that QFG had the effect of inhibiting cardiomyocyte apoptosis. On the basis of established reliable and stable rabbit model of sick sinus syndrome combined with yang-deficiency and blood-stasis syndrome, this research will elaborate effects of QFG improving the TCM syndromes of rabbit SSS model,and discuss the protecting mechanism of QFG on electrophysiological function after the Sino-atrial node (SAN)damaged.Objective:To explore the feasibility and reliability to build a chronic sinus node dysfunction model in rabbit induced by formaldehyde pinpoint wet compressing injecting of sinoatrial node aera,and explore the feasibility to establish a rabbit model of sick sinus syndrome combined with yang deficiency and blood-stasis syndrome via surgery. And to study the effect of Qiangxin Fumai granule on rabbit model combined sick sinus syndrome with yang deficiency and blood-stasis syndromeMethods:1 To establish a rabbit model of sick sinus syndrome:Thirty five rabbits were randomly divided into 2 groups(15 for each group):The formaldehyde wet dressing(FWD) group rabbit SND model was established by contacting a cotton patch with 20% formaldehyde on the sinus node area,the formaldehyde pinpoint wet compressing injection(FPWCI) group rabbit SND model was established by pinpointing and then wet compressing sinus node with a self-made electrode connecting injector.Model success rate, survival rate of both group was evaluated,and the A-A interval,the sinoatrial conduction time(SACT),the sinus node recovery time(SNRT),the corrected sinus node recovery time(CSNRT) were measured at different time points before and after rabbit model established.2.To establish a rabbit model of sick sinus syndrome combined with yang deficiency and blood-stasis syndrome:The TCM syndrome model was established by the method of ice wetting,cold stimulation and subcutaneous injection with adrenaline hydrochloride,and the model of sick sinus syndrome combined with yang deficiency and blood stasis syndrome(combined model) was established by damaging the sinoatrial node with 20% formaldehyde.the general state,temperature,respiratory frequency,heart rate and rhythm,swimming distance and speed in 6 min,and hemorheology index were observed before and after the models established.Compared the TCM syndrome characteristics of the two models according to the clinical diagnostic standard of yang deficiency and blood stasis syndrome.3. To study the effect of Qiangxin Fumai granule on rabbit model:The rabbit model was established by damaging the sinoatrial node with 20% formaldehyde.After the model established,the rabbits received intragastric administration for 7 days.Temperature,respiratory frequency,heart ratec,swimming speed rate in 6 min were observed before and after the administration.Whole blood viscosity on different shear rate, plasma viscosity, erythrocyte aggregation index were measured after the administration. the changes in A A interval, the sinoatrial conduction time(SACT),the sinus node recovery time(SNRT),the corrected sinus recovery time(CSNRT) and the index sinus node recovery time at different phases were measured.Results:1.1 To establish a rabbit model of sick sinus syndrome:The successful rate and survival rate of FPWCI group was higher than FWD group (P<0.01).2.To establish a rabbit model of sick sinus syndrome combined with yang deficiency and blood-stasis syndrome:After the modles established,both two groups of rabbrit had lower temperature,higher respiratory frequency and heart rate,lower swimming distance and speed,and higher hemorheology index.The index as mentioned of both groups were no difference except the heart rate,swimming distance and speed.3. To study the effect of Qiangxin Fumai granule on rabbit model:Compared with model group,the rabbits of each treatment group had higher temperature,lower respiratory frequency,higher heart rate,higher swimming speed rate,lower whole blood viscosity on low shear rate, lower plasma viscosity and lower erythrocyte aggregation index after administration,and there is difference between three treatment groups and model groups(P< 0.01or0.05).And the index as mentioned below has difrerence between in high dose group and in other dose groups(P<0.01 or0.05). Compared with the normal group,the AA interval, SACT,SNRT,CSNRT in the model group, the atropine group, the high-dose KFG group, the middle-dose QFG group and the low-dose QFG group were prolonged significantly(p<0.05 or p<0.01).Compared with the model group, the four electrophysiological parameters abovementioned in four treatment groups were decreased significantly and the Chinese medicine group were superior to the western medicine group (p<0.05 or p<0.01).Conclusion:The method of FPWCI can successfully estabilish rabbit chronic SND model,the electrophysiology function of sinoatrial node after its constitution damaged accord with Sick Sinus Syndrome.And compared with the traditional method,it has higher success rate,survival rate,less damage,and better stabilization.And the combined model established by surgery has no difference with the TCM syndrome model in TCM syndrome,and it conforms to the clinical diagnostic standard of yang deficiency and blood stasis syndrome. Qiangxin Fumai granule can improve symptoms and hemorheology index of rabbits model and it has better effect in high dose group. KFR is beneficial for accelerating the recovery of sinus node autorhythmicity and conduction function so as to protect electrophysiological functions of the sinoatrial node, which may be its electrophysiological mechanism in treatment of Sick Sinus Syndrome.