Effects of β-adrenergic blockade on vasodepressor reaction in patients with vasodepressor syncope

Abstract

The mechanism of vasodepressor reaction induced by head-up tilt test in patients with vasodepressor syncope is not clearly understood. We hypothesized that an abnormal alteration of β-adrenergic transmission could be involved in these patients. We measured plasma catecholamine concentration during tilt and density of β-adrenoceptors and tested the effects of β-adrenergic blockers in the prevention of the vasodepressor reaction in patients with vasodepressor syncope. Ten patients had reproducibly induced vasodepressor syncope (mean 3.1 ± 0.3 episodes in each patient) with head-up tilt (80 degrees) for 10 minutes with isoproterenol infusion (1 to 3 μg/min). Syncope occurred at 6.3 ± 1.7 minutes during tilt with isoproterenol infusion. The plasma norepinephrine concentration before administration of β-blocker was significantly elevated during tilt compared to the supine position (0.347 ± 0.079 ng/ml in supine position with isoproterenol vs 0.468 ± 0.082 ng/ml at 3 minutes of tilt, p < 0.001, and vs 0.503 ± 0.106 ng/ ml at the onset of vasodepressor reaction, p < 0.005; n = 8). Plasma norepinephrine after administration of the selective β 1-adrenergic blocker metoprolol (40 mg/day) was similarly elevated (0.282 ± 0.071 ng/ml in supine position with isoproterenol vs 0.390 ± 0.078 ng/ml at 3 minutes of tilt, p < 0.05, n = 6; and vs 0.547 ± 0.152 ng/ml at the onset of vasodepressor reaction, p < 0.001, n = 3). Plasma norepinephrine after administration of the nonselective β-blocker propranolol (30 mg/day) was not significantly elevated (0.254 ± 0.063 ng/ml in supine position with isoproterenol vs 0.339 ± 0.081 ng/ml at 3 minutes of tilt, p not significant; and vs 0.343 ± 0.079 ng/ml at 10 minutes of tilt, p not significant, n = 6). Metoprolol prevented vasodepressor syncope in 5 of 10 patients; propranolol prevented syncope in all 10 patients ( p < 0.05). Heart rate after administration of propranolol did not increase in either the supine position with isoproterenol or during tilt compared to control tilt and tilt after administration of metoprolol. We abserved no significant differences in the number and afrinity of β-adrenoceptors between five patients with vasodepressor syncope and tive age-matched normal subjects. We conclude that propranolol is far more useful for the prevention of vasodepressor syncope than metoprolol. Our data suggest that β 2-adrenergic transmission may play an important role in the induction of vasodepressor reaction in patients with vasodepressor syncope.