Cardiovascular reactivity to mental stress during gradual withdrawal of chronic postinfarction treatment with metoprolol

Abstract

In 34 patients on double-blind postinfarction treatment with metoprolol 100-200 mg daily (N = 20) or matching placebo, the study treatment was gradually withdrawn during one week. The patients were subjected to mental stress (a modified version of Stroop's colour word conflict test) before and 1 and 12 weeks after the completion of double-blind withdrawal. This stress increased heart rate (P less than 0.001), blood pressures (P less than 0.001) and adrenaline (P = 0.003), but not noradrenaline in venous plasma. In the placebo group similar responses were evoked on all three occasions. In the metoprolol group, heart rate responses were reduced while on treatment. Following withdrawal there was no rebound increase in the heart rate response. Rather, some blockade persisted one week after withdrawal. Twelve weeks after withdrawal heart rate and blood pressure responses to mental stress were normalized. During treatment the metoprolol group had fewer ventricular arrhythmias than the placebo group. Following withdrawal, ventricular arrhythmias during stress increased in 4 patients in the metoprolol group. Plasma adrenaline levels were reduced one week after withdrawal of metoprolol treatment. Plasma noradrenaline levels did not change within either group during the follow-up period. Thus, no rebound increase in cardiovascular reactivity to mental stress was found, in contrast to our previous findings with physical stressors in similar patients participating in this study. These differences in responsiveness after metoprolol withdrawal may be related to different clearance rates for metoprolol in different tissues. Our results indicate that central, presumably supramedullary, cardiovascular control mechanisms involving beta-adrenoceptors recover at a slow rate following withdrawal.