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- Title
Tachyphylaxis with amrinone therapy: association with sequestration and down-regulation of lymphocyte beta-adrenergic receptors.
- Authors
Maisel, Alan S.; Wright, C. Michael; Carter, Steven M.; Ziegler, Michael; Motulsky, Harvey J.; Maisel, A S; Wright, C M; Carter, S M; Ziegler, M; Motulsky, H J
- Abstract
<bold>Study Objective: </bold>To determine whether intravenous therapy with amrinone changes number, location or function of the beta-adrenergic receptors on lymphocytes.<bold>Design: </bold>Case series.<bold>Setting: </bold>Veterans hospital coronary care unit.<bold>Patients: </bold>Eleven patients with decompensated class III or IV heart failure.<bold>Interventions: </bold>A bolus of intravenous amrinone followed by a continuous infusion at 10 micrograms/kg.min for 72 hours.<bold>Measurements and Main Results: </bold>At 24 to 36 hours there was a reduction in pulmonary capillary wedge pressure (35%), right atrial pressure (20%), and systemic vascular resistance (25%) with an increase in cardiac output (30%). By 72 hours all these parameters had returned nearly to baseline levels. This partial cardiovascular tolerance to amrinone was accompanied by a 126% increase in the plasma epinephrine, a 182% increase in norepinephrine, a 31% decrease in the number of beta-adrenergic receptors on lymphocytes, and a 36% decrease in isoproterenol-stimulated cyclicadenosine monophosphate on lymphocytes. The number of sequestered receptors doubled during the treatment, and the extent of sequestration correlated well with the extent of receptor down-regulation.<bold>Conclusions: </bold>The hemodynamic responses to amrinone had virtually returned to baseline by 72 hours. This tolerance was accompanied by increased plasma catecholamines, and a down-regulation, desensitization, and sequestration of beta-adrenergic receptors on lymphocytes. We suggest that these receptor changes also occur in cardiovascular tissues and may in part account for the tolerance to amrinone.
- Subjects
INTRAVENOUS therapy; LYMPHOCYTES
- Publication
Annals of Internal Medicine, 1989, Vol 110, Issue 3, p195
- ISSN
0003-4819
- Publication type
journal article
- DOI
10.7326/0003-4819-110-3-195