Cardiac function during mental stress: cholinergic modulation with pyridostigmine in healthy subjects

Mentally or emotionally stressful situations occur throughout our lives and cause physiological haemodynamic responses. In patients with coronary artery disease, such events can also induce myocardial ischaemia and ventricular arrhythmias, increasing mortality rates. The purpose of the present study was to determine the acute effects of the oral administration of pyridostigmine, a reversible cholinesterase inhibitor and thus an indirect cholinomimetic drug, on echocardiographic variables during mental stress in healthy subjects. A total of 18 healthy young volunteers were subjected to mental stress tests (mental arithmetic and the Stroop colour–word test) 2 h after the oral administration of either placebo or pyridostigmine bromide (45 mg), using a balanced-randomized, double-blind, crossover protocol. During mental stress, heart rate (pyridostigmine, 64±1 beats/min; placebo, 70±1 beats/min; P=0.0003) and diastolic blood pressure (pyridostigmine, 66±2 mmHg; placebo, 79±3 mmHg; P=0.01) were lower in the pyridostigmine group, but systolic pressure was not (pyridostigmine, 124±3 mmHg; placebo, 123±3 mmHg; P=0.40). There were no detectable abnormalities in the left ventricular wall motion score during mental stress, but left ventricular outflow tract mean velocity (pyridostigmine, 0.68±0.02 m/s; placebo, 0.64±0.02 m/s; P<0.05) and mitral inflow velocity deceleration (placebo, 4.05±0.18 m/s²; pyridostigmine, 4.41±0.16 m/s²; P<0.05) were higher in the pyridostigmine group. In conclusion, cholinergic stimulation with pyridostigmine seems to increase left ventricular diastolic function during mental stress in healthy subjects.