Department of Biomedical and Clinical Sciences, L. Sacco Hospital, University of Milan, Milan, Italy IRCCS Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy Biological Sciences Institute, Triangulo Mineiro Federal University, Uberaba, MG, Brazil.
Department of Biomedical and Clinical Sciences, L. Sacco Hospital, University of Milan, Milan, Italy IRCCS Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Cardiovasc Res. 2015 Oct 1;108(1):31-8. doi: 10.1093/cvr/cvv180. Epub 2015 Jun 22.
Bradycardic agents are currently used in the treatment of angina and heart failure; direct information on their effects on cardiac sympathetic nerve activity (SNA) may be relevant to their chronic use. The present study evaluates the effect of pacemaker inhibition on SNA; direct nerve recordings and indirect autonomic indexes are compared.
Experiments were performed in 18 anaesthetized rats. SNA (direct nerve recording) and heart rate variability (HRV) indexes were evaluated in parallel. All parameters were recorded 10 min before to 60 min after administration of the If blocker ivabradine (IVA; 2 mg/kg, i.v.; n = 8) or vehicle (VEH; n = 5). IVA-induced RR interval (RR) prolongation (at 60 min +15.0 ± 7.1%, P < 0.01) was associated with decreased diastolic arterial pressure (DAP; -17.3 ± 8.4%, P < 0.05) and increased SNA (+51.1 ± 12.3%, P < 0.05). These effects were accompanied by increased RR variance (RRσ(2)), which showed strong positive correlation with RR. Frequency-domain HRV indexes (in normalized units) were unchanged by IVA. After baroreceptor reflexes had been eliminated by sino-aortic denervation (n = 5), similar IVA-induced RR prolongation (at 60 min +14.3 ± 5.9%, NS vs. intact) was associated with a larger DAP reduction (-30.9 ± 4.1%, P < 0.05 vs. intact), but failed to affect SNA.
(i) IVA-induced bradycardia was associated with increased SNA, resulting from baroreceptor unloading; if this applied to chronic IVA use in humans, it would be of relevance for therapeutic use of the drug. (ii) Whenever mean HR is concomitantly changed, time-domain HRV indexes should not be unequivocally interpreted in terms of autonomic balance.
目前，缓心剂被用于心绞痛和心力衰竭的治疗；关于它们对心脏交感神经活动（SNA）的影响的直接信息可能与它们的慢性使用有关。本研究评估了起搏器抑制对 SNA 的影响；比较了直接神经记录和间接自主神经指标。
在 18 只麻醉大鼠中进行了实验。同时评估 SNA（直接神经记录）和心率变异性（HRV）指标。所有参数在给予 If 阻滞剂伊伐布雷定（IVA；2mg/kg，iv；n=8）或载体（VEH；n=5）前 10min 记录一次，直至 60min 后。IVA 诱导的 RR 间期（RR）延长（60min 时+15.0±7.1%，P<0.01）与舒张压（DAP）降低（-17.3±8.4%，P<0.05）和 SNA 增加（+51.1±12.3%，P<0.05）有关。这些作用伴随着 RR 方差（RRσ（2））的增加，RRσ（2）与 RR 呈强正相关。IVA 不改变频域 HRV 指标（以归一化单位表示）。在通过窦房结动脉去神经（n=5）消除了压力感受器反射后，IVA 诱导的类似 RR 延长（60min 时+14.3±5.9%，与完整状态相比无统计学意义）与 DAP 更大的降低（-30.9±4.1%，与完整状态相比有统计学意义）有关，但未能影响 SNA。
（i）IVA 诱导的心动过缓与 SNA 增加有关，这是由于压力感受器卸载所致；如果这适用于人类慢性 IVA 应用，那么这与药物的治疗应用有关。（ii）只要平均 HR 同时发生变化，就不能根据时间域 HRV 指标来明确解释自主平衡。
