The protective effect of magnesium on acute catecholamine cardiotoxicity in the neonate.
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.
Caspi
J
J
Division of Cardiovascular Surgery, Hospital For Sick Children, Toronto, Ontario, Canada.
Coles
J G
JG
Benson
L N
LN
Herman
S L
SL
Diaz
R J
RJ
Augustine
J
J
Brezina
A
A
Kolin
A
A
Wilson
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003971:Diastole; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006331:Heart Diseases / Q000139:chemically induced*; D006339:Heart Rate; D008274:Magnesium / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D013552:Swine; D013599:Systole; D016277:Ventricular Function, Left
D000255:Adenosine Triphosphate; D008274:Magnesium; D004837:Epinephrine