Autonomic Nerve Mechanism Of Stress-induced Arrhythmia In Goat

Objective:Stress can leads to SIA including VT,Vf,and increased SCD. Some studies indicated that myocardial electrical unstability indued by changed ANS function or myocardial ischemia are impotant inciting factors of the genesis of SIA.Meanwhile,the change of HRV,TWA,HRT,intracellular calcium concentration,CNS and hereditary factors play important roles in inducing SIA. But some of these factors are downstream reactions of ANS function changes, and some of them may be beyond the mechanism of ANS regulation,the relationship of them needs to be clarified.On the other hand,although there are some evidence showed that ANS is critical for inducing SIA,but many details are still unknown.This Study established a goat stress model and analyzed the changes of ANS and its relation to SIA,and the pathway of sympathetic signals transmiting across the myocardial cell membrane,in order to elucidate the autonomic mechanism of SIA.Methods:15 adult male goats(body weight 18-26 kg)were divided into control,stress and metoprolol groups.Noise and flash light were used for 24 hours to establish the acute stress model.By 24 hours electrocardiogram monitoring,arrhythmia,HRV,TWA were recorded and analyzed.Subsequently, the animals were anesthetized and cervical sympathetic nerves were dissociated bilaterally,after recording the electrical activities of nerves for 20 minutes, open-thoracic surgery were performed,epicardial leads were used to measure ERP in different zone of left atrium and ventricle,in the same time,the induced arrhythmias and AD were recorded.Subsequently,the animals were killed by bloodletting through aorta,the myocardial tissue were kept for preparing the myocardial membrane sample.Myocardialβ-AR density,AC activity and cAMP level were measured by radioligand binding assay and radioimmunoassay. Results:1.ST segment analysis ST segment were within normal range during the sress state.2.Arrhythmias during Holter recording stress and metoprolol groups have more SVPB,SVT and VPB(P＜0.01 or 0.05),and there is no Af,VT,VF and Vf occurring.3.HRV analysis Both SDANN and rMSSD decreased significantly in stress and metoprolol groups,but these indices are higher in metoprolol group than stress group(P＜0.01 or 0.05).Stress group have higher LFn and LF/HF ratio and lower HFn than control and metoprolol groups, and metoprolol guoup have increased LFn,LF/HF ratio and decreased HFn than control group(P＜0.01 or 0.05).LFn,LF/HF value of control group has high-in-daytime and low-in-night model,HFn is on the contrary,but nerther stress nor metoprolol group have similar features.4.The relation between arrhythmias and HRV There is linear relationship between arrhythmia(SVPB,VPB)and LH/HF ratio,correlation coefficient are 0.924,0.877,0.886 and 0.774,0.913,0.885 respectively,regression equation are Y=-100.3+349.7X,Y=-1225.0+805.2X,Y=-99.0+419.4X and Y=-10.6+14.7X,Y=-211.6+110.7X,Y=-33.4+51.6X respectively.5.TWA analysis TWA increased in stress and metoprolol group,but the latter is lower than the former(P＜0.01 or 0.05).6.ERP and its dispersion stress and metoprolol group have shortened ERP and increased ERP dispersion,and stress group have more significant change (P＜0.01).7.EAD analysis stress group have more EAD than the control and metoprolol groups(P＜0.01),but there is no difference between the control and metoprolol group,8.Arrhythmias during ERP measurement Af was only induced in 3 goats of the stress group and 1 goat of metoprolol group,and the incidence of Af are not different.Stress group have more VPB than control and metoprolol group(P＜0.01),there is no difference between the control and metoprolol group. 9.Cervical sympathetic electrical activity analysis the peak value in 51Hz,54Hz,148Hz and the power of 51-250Hz,51-140Hz,140-160Hz,160-250Hz are similarly and significantly increased in stress and metoprolol group(P＜0.05 or 0.01).In control group,there is no remarkable differences of peak value and power between the sympathetic nerves on the two sides of neck,but in stress and metoprolol groups,the right sympathetic nerve has higher peak value and power (P＜0.05 or 0.01).10.Myocardialβ-AR density stress and metoprolol groups have increased receptor density than control group,but there is no significant difference between the control and the metoporolol group,and K_D value is not different either.11.AC activity and myocardial cAMP level stress group has higher AC activity and cAMP level than the control and metoprolol groups (P＜0.01 or 0.05),and these indices of metoprolol group also higher than that of control group(P＜0.05).Conclusion:ANS play an important role in the genesis of SIA.Stressed goats have increased sympathetic activity and decreased vagal tone,and lost the normal circadian rhythm,which may induced shortened ERP and increased ERP dispersion and TWA amplitude,and ultimately induced SIA.The different drive of sympathetic nerves bilaterally may be the most important cause leading to increased dispersion of ERP and repolarization.Metoprolol improve the abnomal autonomic function of heart in stressed goats,and subsequently improve the abnormality of HRV,TWA,ERP dispersion,and enhance the myocardial electrical stability,and decrease the genesis of SIA,But metoprolol cannot inhibit the whole stress reaction of the body,and cannot inhibit sympathetic activity and imbalance of bilateral sympathetic drive,and cannot recover the normal circadian rhythm of HRV,so,the goats of metoprolol group still have relatively high incidence of SIA.β-AR—G protein—AC—cAMP chain is the important but not the only pathway by which the stress signals are transmitted across the myocardial cell membrane.