The Journal of Thoracic and Cardiovascular Surgery, Vol 105, 525-531, Copyright © 1993 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
The protective effect of magnesium on acute catecholamine cardiotoxicity in the neonate
J Caspi, JG Coles, LN Benson, SL Herman, RJ Diaz, J Augustine, A Brezina, A Kolin and GJ Wilson
Division of Cardiovascular Surgery, Hospital For Sick Children, Toronto, Ontario, Canada.
Neonates undergoing heart surgery are exposed to high levels of circulating
catecholamines. Our objective was to determine to what extent
administration of magnesium counters epinephrine-induced cardiotoxicity. We
assessed left ventricular function (pressure-volume data obtained by the
conductance catheter/micromanometer technique) and ultrastructure in
newborn pigs 3 to 5 days of age before and after administration of
epinephrine alone (2 micrograms/kg/min, group A, n = 6) and simultaneously
with magnesium sulfate (8 mmol/L, 5 ml/hr, group B, n = 6). Plasma levels
of magnesium were maintained at 200% to 250% of control, and ionized
calcium was maintained at normal levels. During administration of
epinephrine, there was a significant increase in end- systolic elastance
from 8.9 +/- 2 to 15 +/- 3 mm Hg/ml in group A and from 7.8 +/- 2 to 16 +/-
3 mm Hg/ml in group B (p < 0.05). This increase was accompanied by an
increase in chamber stiffness index (p < 0.05) and shortening of the
time constant of isovolumic relaxation (p < 0.05; group A, 19 +/- 3 to
13 +/- 3 msec; Group B, 20 +/- 2 to 15 +/- 2 msec). After epinephrine was
discontinued, however, systolic and diastolic indexes returned to baseline
levels in group B, whereas group A exhibited a significant reduction in
end-systolic elastance (5 +/- 1 mm Hg/ml; p < 0.05) and an increase in
chamber stiffness index (0.7 +/- 0.08 versus 0.4 +/- 0.1 ml-1; p < 0.05)
and time constant (25 +/- 1 versus 19 +/- 3 msec). Left ventricular
dysfunction in group A was associated with focal sarcolemmal rupture and
mitochondrial swelling, whereas only minor reversible changes
(microvesicular lipid accumulation) were seen in group B. We conclude that
magnesium has a protective effect against epinephrine-induced
cardiotoxicity because of its blocking action on calcium influx of ionized
calcium and could be of therapeutic benefit in the perioperative period.
