Cholinergic stimulation with pyridostigmine prevents the impairment in ventricular function during mental stress in coronary artery disease patients.

Mental stress causes physiological autonomic adjustments that may trigger myocardial ischemia and ventricular dysfunction in patients with coronary artery disease. Thus, it was hypothetized that cholinergic stimulation may counteract the ventricular dysfunction provoked by mental stress in coronary disease. Six patients with coronary disease underwent a randomized, double-blind, cross-over, and placebo-controlled protocol in which they received placebo or a single dose of pyridostigmine bromide (45 mg p.o.), a reversible cholinesterase inhibitor, and thus, a cholinomimetic agent 2 h before a standard mental stress task (Stroop color-word test), while hemodynamic and echocardiographic variables were continuously monitored. There were no signs of myocardial ischemia on ECG during mental stress under PYR or placebo. Heart rate and blood pressure increased during mental stress (P<0.01) similarly with placebo and PYR (P>0.05). There were no ventricular wall motion abnormalities during mental stress with either placebo or PYR, but mental stress decreased ejection fraction (pre 63+/-2%, stress 57+/-2%; P=0.004) and impaired the indices of diastolic ventricular function. On the other hand, PYR prevented the fall in ejection fraction (pre 62+/-2%, stress 64+/-2%; P=0.13) and in the indices of diastolic function (P>0.05). In conclusion, cholinergic stimulation with pyridostigmine prevented the impairment in myocardial function during mental stress in patients with coronary artery disease.

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/s(2); pyridostigmine, 4.41+/-0.16 m/s(2); 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.