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.
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. ;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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