Mitral valve prolapse with symptoms of beta-adrenergic hypersensitivity

Beta2-adrenergic receptor supercoupling with desensitization on isoproterenol exposure
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      Autonomic nervous system dysfunction has recently been identified in a subset of patients with mitral valve prolapse. These autonomic nervous system abnormalities may correspond, in part, to biochemical alterations in beta-adrenergic receptors. Nine women with mitral valve prolapse and symptoms and signs of beta-adrenergic hypersensitivity and seven normal volunteer women were studied. Quiet standing (five minutes) increased both heart rate and plasma norepinephrine (p < 0.05) in symptomatic patients with mitral valve prolapse compared with normal subjects. The dose of isoproterenol required either to increase heart rate 25 beats/minute (0.5 ± 0.3 μg versus 1.0 ± 0.3 μg) or to decrease mean arterial pressure 20 mm Hg (11.1 ± 4.8 versus 78.2 ± 25.2 μg) was significantly less in the patients with mitral valve prolapse than in the volunteers. Symptomatic patients with mitral valve prolapse were desensitized by a four-hour isoproterenol infusion, whereas sensitivity in normal control subjects did not change. In the patients with mitral valve prolapse, baseline beta-adrenergic receptor coupling was elevated compared with that in control subjects (220 ± 7 versus 81 ± 2; p < 0.001). Isoproterenol infusion induced uncoupling in these patients (KL/KH = 35 ± 3, p < 0.05) but did not alter coupling in normal volunteers. This study demonstrates physiologic and pharmacologic beta-adrenergic hypersensitivity in vivo directly corresponding to biochemical supercoupling in a subset of patients with mitral valve prolapse.
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