Effects of stress and beta 1 blockade on the ventricular depolarization gradient of the rate modulating pacemaker

Prism-CLR is a closed loop, rate modulating pacemaker that uses ventricular depolarization gradient (Gd) to continuously adjust heart rate. Heart rate response to a formal mental stress protocol, esmolol (500 mcg/kg bolus, 75-125 mcg/kg/min infusion), and mental stress during esmolol infusion were studied in six patients to investigate if Gd and paced heart rate response are under direct beta-adrenergic control. Paced heart rates increased in response to mental stress in a physiological manner (P less than 0.001). Response to esmolol infusion was paradoxical, with increased paced heart rates during esmolol bolus and infusion (P less than 0.05). There was no significant alteration in either systolic or diastolic blood pressure during mental stress or esmolol infusion (P greater than 0.05). Paradoxical increase in paced heart rates during esmolol administration suggests a primary or secondary effect of esmolol to decrease the ventricular depolarization gradient. This hypothesis was supported in four dog studies in which direct Gd measurements were made during esmolol infusion. Mental stress during esmolol infusion resulted in significantly increased paced heart rates (esmolol effect) with blunted changes in heart rate in response to the mental stress. The results of this study suggest that the physiological rate response during mental stress is attributable to sympathetic autonomic response.