Journal of Applied Physiology, Vol 51, Issue 5 1204-1213, Copyright © 1981 by American Physiological Society
Acute pulmonary hemodynamic effects of intravenous copper sulfate: role of alpha-adrenergic system
T. Ahmed, A. Januszkiewicz, P. Eyre, M. J. Robinson and M. A. Sackner
We investigated the acute pulmonary hemodynamic effects of intravenous
copper sulfate (CuSO4) infusion and its mechanism of action in six groups
of conscious sheep (total 40). After 300 mg CuSO4 alone, mean pulmonary
artery pressure (Ppa) increased from 10.3 to 22.5 Torr and pulmonary artery
wedge pressure (Ppaw) from 3.5 to 7.6 Torr, whereas systemic arterial
pressure (Psa) increased from 95 to 102 Torr. Cardiac output (Qp) decreased
from 4.7 to 3.3 l/min. Pulmonary vascular resistance (PVR) and systemic
vascular resistance (SVR) increased to 320 and 160% of base line,
respectively. The hemodynamic changes correlated well with serum copper,
which increased from a base-line value of 0.12 to 3.5 mg/dl after the
CuSO4. Serum dopamine beta-hydroxylase increased from 3.2 U/l before CuSO4
injection to 5.7 after its administration, signifying activation of
adrenergic nervous system. H1-histamine receptor blockade with
chlorpheniramine failed to prevent the effects of CuSO4. Pretreatment with
methysergide, a serotonin antagonist, partially attenuated the effects of
CuSO4. Phenoxybenzamine, an alpha-adrenergic receptor blocker, and
6-hydroxydopamine, a catecholamine depleting agent, completely blocked the
effects of CuSO4. beta-Adrenergic receptor blockade with propranolol
enhanced the effects of CuSO4. We conclude, that, in conscious sheep, acute
infusion of CuSO4 caused a marked reversible increase in PVR with a slight
transient increase in SVR, and this pulmonary hypertension was produced by
stimulation of the alpha-adrenergic nervous system.
