Debora De-Ping Lee

Pathogenesis of cardiac neuro-myopathy in Chagas' disease and the role of the autonomic nervous system

baroreceptor reflex in Chagasic patients with or without congestive heart failure, and comparing them with patients with congestive heart failure of different aethiology and with normal subjects.

Noradrenergic activity and silent ischaemia in hypertensive patients with stable angina: effect of metoprolol.

30 patients (10 normotensive, 20 hypertensive) with stable angina and positive treadmill exercise tests entered a double-blind, placebo-controlled crossover trial of metoprolol, 100 mg twice daily. At the end of each treatment phase, blood pressure was monitored for 24 h and Holter and real-time electrocardiographic (ECG) monitoring were carried out and an activity diary kept for 48 h. Blood samples for catecholamine measurement were taken after 30 min supine, 60 min standing, and at the first silent ischaemic event, triggered by the real-time ECG monitor, by means of an ambulatory blood withdrawal pump. Metoprolol lowered blood pressure and heart rate in both normotensive and hypertensive subjects, and reduced the frequency and duration of silent ischaemic episodes in hypertensive subjects. Plasma noradrenaline measured during silent ischaemia while the patients were resting was significantly higher than the control supine level without ischaemia. These findings suggest that noradrenergic hyperactivity may have a role in coronary vasoconstriction and that treatment which neutralizes sympathetic tone may be especially beneficial in treatment of silent ischaemia in hypertensive patients.

Physical Stressors and Pharmacologic Manipulations

Muscular work increases oxygen demand; as a result, changes in heart rate, stroke volume, cardiac output, and peripheral vascular resistance, enhance blood flow to the active muscle groups. Cardiac output and flow to the exercising muscles increase linearly, while resistance increases in vascular beds of resting muscles. Centers in the cerebral cortex are linked to cardiovascular regulation via the brain stem, and accommodate both isometric and isotonic exercise (Stone, Dormer, Foreman, Thies, & Blair, 1985). Further, afferent fibers from the exercising muscles are integrated to mediate central control of the circulation. The various components involved in cardiovascular control during exercise, including the “central command” concept, are indicated in Figure 1.

Effects of celiprolol on plasma renin, aldosterone, norepinephrine and epinephrine in primary hypertension

Celiprolol is a newly developed cardioselective beta-blocking agent with mild beta 2-agonist and weak alpha 2-antagonist properties. To evaluate the acute (2.5 hours) and chronic (2 weeks) effects of celiprolol (400 mg once a day) on plasma renin, aldosterone, norepinephrine and epinephrine, 20 patients with mild to moderate primary hypertension were studied in a double-blind placebo-controlled crossover trial. Two and one-half hours after the first dose of both placebo and celiprolol, supine and standing measurements of blood pressure showed a significant reduction, whereas plasma norepinephrine increases were comparable with baseline values. Placebo and celiprolol produced similar changes on supine blood pressure and plasma norepinephrine. In 9 patients celiprolol decreased plasma renin (from a mean +/- standard deviation of 1.09 +/- 0.35 to 0.77 +/- 0.52 ng/ml/hr, p less than 0.05) and aldosterone (from 9.2 +/- 3.7 to 6.7 +/- 3.9 ng/dl, p less than 0.05) acutely both supine and standing, but placebo did not change these parameters. Celiprolol increased pulse rate supine (but not standing) as compared with baseline values. After 2 weeks of celiprolol therapy, blood pressure was decreased both supine and standing compared with placebo in 18 patients (140 +/- 18/88 +/- 8 vs 149 +/- 18/94 +/- 7, 136 +/- 18/91 +/- 6 vs 142 +/- 20/97 +/- 9 mm Hg, respectively, each p less than 0.05), without a change of pulse rate when supine and with a reduction when standing. There were no significant changes of plasma renin, aldosterone, norepinephrine and epinephrine levels during chronic therapy compared with placebo.