Tachyphylaxis with amrinone therapy: association with sequestration and down-regulation of lymphocyte beta-adrenergic receptors.
OBJECTIVE
To determine whether intravenous therapy with amrinone changes number, location or function of the beta-adrenergic receptors on lymphocytes.


METHODS
Case series.


METHODS
Veterans hospital coronary care unit.


METHODS
Eleven patients with decompensated class III or IV heart failure.


METHODS
A bolus of intravenous amrinone followed by a continuous infusion at 10 micrograms/kg.min for 72 hours.


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 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.


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 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.
Maisel
A S
AS
University of California, San Diego.
Wright
C M
CM
Carter
S M
SM
Ziegler
M
M
Motulsky
H J
HJ
D000368:Aged; D000676:Amrinone / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis; D004361:Drug Tolerance; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013618:Tachyphylaxis
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000676:Amrinone