Alan S. Maisel, MD; C. Michael Wright, MD; Steven M. Carter; Michael Ziegler, MD; Harvey J. Motulsky, MD
Study Objective: To determine whether intravenous therapy with amrinone changes number, location or function of the β-adrenergic receptors on lymphocytes.
Design: Case series.
Setting: Veterans hospital coronary care unit.
Patients: Eleven patients with decompensated class III or IV heart failure.
Interventions: A bolus of intravenous amrinone followed by a continuous infusion at 10 µg/kg · min for 72 hours.
Measurements and Main Results: 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 β-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.
Conclusions: 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 β-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.
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Maisel AS, Wright CM, Carter SM, Ziegler M, Motulsky HJ. Tachyphylaxis with Amrinone Therapy: Association with Sequestration and Down-Regulation of Lymphocyte Beta-Adrenergic Receptors. Ann Intern Med. 1989;110:195-201. doi: 10.7326/0003-4819-110-3-195
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Published: Ann Intern Med. 1989;110(3):195-201.
Cardiac Diagnosis and Imaging, Cardiology, Heart Failure, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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