Carnitine deprivation adversely affects cardiac performance in the lipopolysaccharide- and hypoxia/reoxygenation-stressed piglet heart

Sepsis and hypoxia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine a nd develop low carnitine plasma and tissue levels. Because of its high meta bolic rate and dependence on fatty acids for energy, the newborn heart may be particularly vulnerable to stress in the face of an inadequate carnitine supply. To investigate whether carnitine deprivation affects cardiac perfo rmance under stress, 23 neonatal piglets received parenteral nutrition for 23 weeks that was either carnitine free (CARN -) or supplemented (CARN +) w ith L-carnitine (400 mg/L). Bacterial endotoxin (lipopolysaccharide (LPS), 250 mu g/kg intravenous bolus) or saline vehicle was administered to anesth etized piglets 3 h prior to study of isolated perfused hearts. Left ventric ular systolic pressure (LVSP), left ventricular end diastolic pressure, and left ventricular developed pressure (LVDP) were measured in vitro under ae robic, hypoxic, and reoxygenation conditions in all animals. Plasma and tis sue carnitine values were lower in CARN - than in CARN + piglets. In hearts from LPS-treated animals prior to hypoxia, there was no difference in vent ricular compliance between CARN - and CARN + groups. LVSP and LVDP were low er in CARN - than CARN + hearts. During hypoxia, LVSP and LVDP fell, but le ft ventricular end diastolic pressure increased in hearts from both LPS- an d saline- treated piglets. Reoxygenation led to poorer recovery in CARN - t han CARN + hearts from LPS-treated animals, but not from saline controls. D uring hypoxia/reoxygenation, lactate efflux initially rose and then fell, w hile carnitine efflux increased continually. Acetyl- and medium-chain acylc arnitines were detected in the coronary effluent. Our findings suggest that carnitine deprivation diminishes heart carnitine concentrations and impair s cardiac recovery from combined endotoxic and hypoxic stress. Possible mec hanisms include reduced acyl buffering and/or impaired transport of fatty a cyl groups into mitochondria.