Autonomic nerve stimulation (ANS) can modulate ventricular force by direct effects on contractility and indirectly by altering heart rate (HR). Whilst there is agreement that sympathetic nerve stimulation (SNS) has a positive inotropic effect, controversy remains whether there is a significant direct effect from vagus nerve stimulation (VNS) on contractility. Heart rate alone can alter contractile force with a positive force-frequency relationship (FFR) in most species. The relative contribution between the effects on HR and contractility in the resultant inotropic change from ANS has not been fully investigated. It was the aim of this study to examine this in isolated hearts with intact dual autonomic innervation.

Adult NZW rabbits (2.2-2.5 kg, n = 8) were humanely killed with an overdose of anaesthetic. Hearts were isolated and the thoracic spine with sympathetic outflow was preserved whilst both vagus nerves were isolated at the mid-cervical region. The preparation was perfused with Tyrode solution (37 °C) in constant flow Langendorff mode via the descending aorta. Left ventricular pressure (LVP) was measured via an intraventricular balloon during: (1) SNS and VNS without pacing when HR was allowed to vary to study effects on HR and contractility (Contr). During SNS, the sympathetic outflow was stimulated at 2 (low, L), 5 (medium, M) and 10 Hz (high, H). During VNS, the cervical vagi were stimulated 2 (L), 5 (M) and 7 Hz (H); (2) constant right ventricular pacing (240 b.p.m.) with either SNS or VNS to study contractility alone, and (3) constant right atrial pacing at a range of HR (120-300 b.p.m.) without background ANS to study FFR. Parameters (mean ± S.E.M.) were measured at steady state and analysed using ANOVA.

Our results were as follows. (1) With L, M and H SNS, HR/LVP increased significantly from baseline values of 142 ± 7 b.p.m./51 ± 5 mmHg to 163 ± 4/57 ± 5, 189 ± 5/ 61 ± 4 and 219 ± 6/68 ± 5, respectively. With L, M and H VNS, HR/LVP decreased from baseline values of 141 ± 12 b.p.m./52 ± 7 mmHg to 129 ± 13/51 ± 8, 115 ± 16/49 ± 8 and 107 ± 16/47 ± 8, respectively. (2) During constant ventricular pacing, SNS caused a significant (P < 0.001) frequency-dependent increase in LV pressure from 51 ± 3 to 54 ± 3 (L), 59 ± 3 (M) and 63 ± 3 (H) mmHg. LV pressure was unaltered during VNS at the frequencies studied. (3) FFR was positive up to around 140 b.p.m., above which LVP decreased with higher HR. Figure 1 shows data from the above three sets of experiments normalised to baseline HR and LVP and aligned for comparison.

In the isolated, innervated rabbit heart, SNS increased LVP predominantly by direct effects on contractility whilst VNS decreased LVP predominantly by indirect effects on HR.This work was supported by the British Heart Foundation.

Figure 1. Normalised LVP and HR data.