The Effects Of Cardiac Autonomic Modulation On Ventricular Arrhythmias

Background:Cardiac autonomic modulation was involved in the etiology of ventricular arrhythmias (VAs). For idiopathic VAs without organic heart diseases, both sympathetic activation and vagal overactivity seem to be evocative for VAs under different circumstances. However, for most VAs in the setting of organic heart diseases, sympathetic activation and/or vagal withdrawl can facilitate their occurrences. And it was widely proved that sympathetic-inhibitory and/or vagal-enhancing autonomic interventions were effective in treating organic VAs.Objective:1. To investigate the effects of autonomic control on idiopathic VAs;2. To investigate the effects of autonomic control on organic VAs;3. To investigate the effects of ganglionated plexus (GP) stimulation-based autonomic intervention on the occurrence of VAs after ischemia/reperfusion (I/R) injuries.Materials and methods:1. Clinical investigation:162patients with idiopathic premature ventricular contractions (PVCs)(PVC group),53patients with coronary heart diseases (CHD) and PVCs (CHD+PVC group),31healthy controls (Normal Control group), and27CHD patients without PVCs (CHD control group) were enrolled. Holter ECG was used to evaluate occurrence of VAs. Heart rate variability (HRV) and heart rate turbulence (HRT) were calculated to represent cardiac autonomic tone. PVCs were divided into three groups based on the relationships between hourly PVC density and hourly mean HR. PVCs with their densities positively related to HR were defined as sympathetic PVC (S-PVC), PVCs with their densities negatively related to HR were defined as vagal PVC (V-PVC), and PVCs whose densities had no evident relationships with HR were defined as heart rate-independent PVC (I-PVC). Different autonomic tones in the four groups were compared and the relationships between PVC frequency, heart rate (HR) and HRV indices were analyzed. Furthermore, changes in autonomic tone in30min before the onset of typical PVC episodes were investigated.2. Animal experiment:21mongrel dogs were randomly divided into GP stimulation (GP-S) group (N=11) and control group (N=10). The left anterior descending artery (LAD) was occluded for1h and then reopened to cause I/R injury. Low-level electrical stimulation (20Hz, duration0.1ms, causing10%decrease in sinus rate) was performed continuously for1h before LAD occlusion in GP-S group. Ventricular effective refractory period (ERP) was measured at baseline and after GP-S respectively. Holter ECG was performed to calculate HRV at baseline and after GP-S and to analyze the occurrences of VAs during1h after reperfusion.Results:1. For idiopathic PVCs,74cases of S-PVC,57cases of V-PVC and31cases of I-PVC were enrolled. Different circadian features were observed in three types of PVCs. S-PVCs mostly occurred during daytime, V-PVCs mainly occurred at night, while I-PVCs had no evident circadian rhythms. PVC density was positively associated with sympathetic indice (LF/HF) and negatively with vagal indices (HF and HF nu) in S-PVC group while this trend was opposed in V-PVC group. And in I-PVC group no significant relationship was found. Before the onset of typical PVC episodes, mean RR intervals and HF nu decreased significantly and LF/HF showed an increasing trend in S-PVC group, while both mean RR intervals and HF increased significantly in V-PVC group. No significant differences in PVC densities, origins, and incidences of multiform PVCs, couplets and ventricular tachycardia (VT) were found among the three groups. In addition, PVC patients with couplets or high Lown classifications (4a,4b) had significantly lowered HRT and Logistic regression showed that patients with impaired HRT were significantly more likely to have couplets.2. Compared with PVC group and normal control group, patients in CHD+PVC group and CHD control group had significantly lower HRV and HRT, and the vagal indice (HF) was evidently decreased. No differences in HRV or HRT between CHD+PVC group and CHD control group were observed. Organic PVCs accompanied with CHD can also be divided into three types as described above and were mainly S-PVCs which were related to sympathetic activation. In comparison to idiopathic PVCs, organic PVCs had significantly higher incidences of multiform PVCs and couplets. And there was a trend that VT occurred more frequently in organic PVCs. In addition, PVCs of Lown2were significantly fewer and PVCs of Lown3were significantly more in organic PVCs compared with idiopathic PVCs.3. In a canine model of I/R injuries, GP-S caused significant increases in ventricular ERP and vagal indice (HF nu), as well as an evident decrease in sympathetic tone (LF/HF). Compared with control group, the numbers of PVCs, salvos, and VT runs were significantly reduced in GP-S group. And the incidences of salvo and VT in GP-S group were significantly lower compared with control group.Conclusions:1. Idiopathic PVCs might be classified into S-PVC, P-PVC and I-PVC based on their relationships with HR. S-PVC may be caused by sympathetic activation while V-PVC may be related to vagal overactivity. Therefore in the treatment of PVCs the influences of autonomic modulation should be taken into consideration. In addition, the malignancy of idiopathic PVCs might be related to the impairment in cardiac autonomic modulation.2. Impairment of autonomic modulation was significant in CHD patients and was mainly vagal withdrawl. Organic PVCs accompanied with CHD were mainly S-PVCs which were related to sympathetic activation. Compared with idiopathic PVCs, organic PVCs were more malignant with higher incidences of multiform PVCs and couplets.3. In a canine model of I/R injuries, GP-S significantly enhanced vagal tone and inhibited sympathetic tone. GP-S also increased ventricular ERP and showed protective effects against ventricular arrhythmias post I/R injuries. This GP stimulation-based autonomic intervention might be a novel therapy to protect against ventricular arrhythmias post I/R injuries.