The effects of chronic ivabradine administrationon cardiovascular autonomic control during acute vagal stimulation

Introduction: The heart rate (HR) is under the strict control of the autonomic nervous system (ANS), parti-ally via ANS interactions with I(f) current activity. By selectively blocking the I(f) current, ivabradine blunts the tachycardic response to acute sympathetic stimula-tion. However, the effects of ivabradine administration on the HR response to acute vagal stimulation remain unknown.

Objective: To evaluate the effects of chronic ivabradi-ne administration on systolic blood pressure (SBP) and HR during acute in vivo and in vitro parasympathetic stimulation.

Methods: Wistar male rats were divided into two groups: Control (n=7) and IVA (n=8), which recei-ved ivabradine 10 mg/kg/day in the drinking water for three consecutive weeks. The right vagus nerve was iso-lated, sectioned, and the distal end was stimulated at 2, 5, 10, and 20 Hz for 15 s, with a between-stimulations free interval of 5 min. The HR and SBP were assessed at baseline and during each stimulation. At the end of the stimulation protocol, the right atrium was isolated and the spontaneous sinus node discharge rate was assessed in vitro at progressively higher carbamylcholine con-centrations (10-9 to 10-6 mol/L).

Results: At baseline, IVA rats presented similar SBP (p=0.27) and significantly lower HR (p=0.02) compa-red with the Control rats. In both Control and IVA rats, SBP decreased progressively during the four stimula-tion protocols (both p<0.0001), but the drop in SBP was significantly lower in the IVA rats (all p<0.05). In the Control rats, a significant progressive decrease in HR was also noticed (p<0.0001), whereas in the IVA rats, HR was not affected by vagus nerve stimulation (p=0.11). Carbamylcholine administration induced a progressive decrease in spontaneous sinus node dis-charge rate in both groups (both p<0.0001).

Conclusions: This study demonstrates that long-term ivabradine administration attenuates the HR-lowering effect of in vivo parasympathetic activation and indi-cates that these ivabradine-parasympathetic interacti-ons are likely to occur at presynaptic level. These data suggest that ivabradine may be of benefit in patients with exaggerated cardioinhibitory response to vagal activation.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)