Dobutamine alters carnitine metabolism in the neonatal piglet heart.
The use of inotropic agents to support the neonatal heart after sepsis or hypoxia increases cardiac energy demand. Carnitine plays a vital role in energy, fuel metabolism. To test the hypothesis that inotropic agents affect carnitine metabolism, hearts from sow-fed piglets were isolated and perfused with an oxygenated buffer containing glucose and palmitate. Increasing dosages of dobutamine (DOB 2.5-15 microg/Kg body wt per min, 0.007-0.044 micromol/kg per min) or saline vehicle (SAL) were administered. Heart rate (HR), left ventricular systolic (LVSP) and end diastolic pressures (LVEDP) were measured. Left ventricular developed pressure (LVDP = LVSP-LVEDP) and pressure-rate product (LVDP x HR) were calculated. Coronary effluent was collected to measure flow and metabolites. Heart tissue samples were collected for metabolite analysis.


RESULTS
DOB increased HR, LVEDP and the pressure-rate product [LVDP x HR]. Mean lactate production increased in DOB, but not in SAL control hearts, and was correlated with heart acylcarnitine, but not with coronary flow. Tissue acylcarnitine levels were higher in the DOB than in the SAL group. Plasma total carnitine was correlated with [LVDP x HR] and LVDP, but not with HR. The findings demonstrate that DOB alters myocardial carnitine metabolism and suggest that carnitine status may affect cardiac response to inotropic agents.
Azuero
Rodrigo
R
Department of Pediatrics, Tulane Medical Center, New Orleans, LA 70112, USA.
Debata
Chittaranjan
C
Quinn
Marie
M
McDonough
Kathleen
K
Thomson
Jessica
J
Penn
Duna
D
D000818:Animals; D000831:Animals, Newborn; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D002316:Cardiotonic Agents; C116917:acylcarnitine; D004280:Dobutamine; D002331:Carnitine