Vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart

Abstract

1. Studies of the effect of vagus nerve stimulation on ventricular myocardial function in mammals are limited, particularly in the human. 2. The present study was designed to determine the effect of direct electrical stimulation of the left vagus nerve on left ventricular contractile state in hearts paced at 10 % above the natural rate, in anaesthetised pigs and anaesthetised human subjects undergoing open chest surgery for coronary artery bypass grafting. 3. Contractility of the left ventricle was determined from a series of pressure-volume loops obtained from a combined pressure and conductance (volume) catheter placed in the left ventricle. From the measurements a regression slope of the end-systolic pressure-volume relationship was determined to give end-systolic elastance (Ees), a load-independent measure of contractility. 4. In six anaesthetised open chest pigs, stimulation of the peripheral cut end of the left cervical vagus nerve induced a significant decrease in Ees of 26 +/- 14 %. 5. In nine patients electrical stimulation of the left thoracic vagus nerve close to its cardiac branch resulted in a significant drop in Ees of 38 +/- 16 %. 6. The effects of vagal stimulation were blocked by the muscarinic antagonist glycopyrronium (5 mg kg(-1)). 7. Administration of the beta-adrenoreceptor antagonist esmolol (1 mg kg(-1)) also attenuated the effect of vagal stimulation, indicating a degree of interaction of vagal and sympathetic influences on contractility. 8. These studies show that in the human and pig heart the left vagus nerve can profoundly decrease the inotropic state of the left ventricular myocardium independent of its bradycardic effect.

Figure 1. The effect of left cervical vagal nerve stimulation on the end-systolic pressure-volume relationship in the pig

Pig 6, atrioventricular pacing at a rate of 130 bpm. Inferior vena cava occlusion, providing a family of pressure-volume loops (7) without (a) and with (B) vagal stimulation. A, end-systolic elastance (Ees) = 3.23 mmHg ml⁻¹, r²= 0.99; B, Ees = 2.44 mmHg ml⁻¹, r²= 0.97 (regression line drawn between the end-systolic pressure-volume points of each loop).

Figure 3. The effect of left thoracic vagal nerve stimulation on the end-systolic pressure-volume relationship in one human

Patient 4, atrioventricular pacing at a rate of 100 bpm. Inferior vena cava occlusion, providing a family of pressure-volume loops (8) without (a) and with (B) vagal stimulation. A, Ees = 4.04 mmHg ml⁻¹, r²= 0.99; B, Ees = 3.01 mmHg ml⁻¹, r²= 0.96 (regression line drawn between the end-systolic pressure-volume points of each loop).

Figure 2. Negative inotropic effect of vagal stimulation in pigs

Bar graph of mean value of Ees, indicating contractility, for all pigs with (VS) and without (baseline) vagal stimulation (P < 0.002).

Figure 4. Change in inotropic state of left ventricle during vagal stimulation in humans

Graph shows change in contractility (vertical axis) from baseline Ees with vagal stimulation (VS) in humans (P < 0.006).