Heart rate independence of catecholamine-induced myocardial damage in the newborn pig.
Neonates undergoing heart surgery are exposed to high levels of circulating catecholamines. Our objective was to determine to what extent epinephrine (E)-related cardiotoxicity can be attributed to induced tachycardia. We assessed left ventricle function by pressure-volume data obtained by conductance catheter/micromanometer technique and correlated it with ultrastructure in newborn piglets (3 to 7 d old). Group A (n = 6) received E (1 microgram/kg/min) for 2 h, whereas group B piglets (n = 6) were atrially paced at a rate (220/min) matched to group A. Left ventricle peak systolic pressure and stroke work were significantly higher (p < 0.05) in group A. End-systolic elastance increased during E infusion (70%) versus no significant change in group B. After 2 h of E infusion, end-systolic elastance was significantly reduced in group A from 9.8 +/- 3.5 to 5 +/- 2.4 mm Hg/mL (p < 0.05). Chamber stiffness index increased during E infusion from 0.36 +/- 0.2 to 0.6 +/- 0.3 mL-1 (p < 0.05) and remained elevated (0.58 +/- 0.2 mL-1) after E infusion was discontinued versus no change in group B. E-induced left ventricle dysfunction was associated with scattered but irreversible ultrastructural changes consisting of sarcolemmal rupture and loss of mitochondrial architecture, whereas only minor reversible changes such as microvesicular lipid accumulation and mitochondrial swelling were seen in group B. We conclude that E cardiotoxicity in the neonate is independent of induced tachycardia.
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
Act
J A
JA
Wilson
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects*; D008854:Microscopy, Electron; D009638:Norepinephrine / Q000097:blood; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology
D000255:Adenosine Triphosphate; D009638:Norepinephrine; D004837:Epinephrine