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

1. Studies of the effect of vagus nerve stimulation on ventricular myocardi al function in mammals are limited, particularly in the human. 2. The present study was designed to determine the effect of direct electri cal stimulation of the left vagus nerve on left ventricular contractile sta te in hearts paced at 10 % above the natural rate, in anaesthetised pigs an d anaesthetised human subjects undergoing open chest surgery for coronary a rtery bypass grafting. 3. Contractility of the left ventricle was determined from a series of pres sure-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 g ive end-systolic elastance (Ees), a load-independent measure of Contractili ty. 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 antagoni st glycopyrronium (5 mg kg(-1)). 7. Administration of the beta -adrenoreceptor antagonist esmolol (I 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 myocard ium independent of its bradycardic effect.