Carnitine deprivation adversely affects cardiovascular response to bacterial endotoxin (LPS) in the anesthetized neonatal pig.
Sepsis and endotoxemia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine. To investigate whether carnitine deprivation affects the neonate's ability to respond to endotoxin, 19 newborn piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN-) or supplemented (CARN+) with L-carnitine (400 mg/L). Cardiovascular performance, i.e., heart rate; blood pressure (BP); cardiac output (CO); systemic vascular resistance (SVR), and metabolic response, i.e., plasma glucose; lactate; tumor necrosis factor alpha; tissue nitric oxide; and urinary nitrites, were studied serially in anesthetized piglets for 3 h after endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or vehicle administration. Plasma and tissue carnitine values were lower in CARN- than in CARN+ piglets. Prior to LPS, no differences were found for most parameters (excepting lower diastolic BP and SVR in CARN- animals). Systolic, diastolic, and mean BP fell after LPS but recovered by the end of the experiment. Nadirs were lower in CARN- than in CARN+ piglets. CO tended to be higher in CARN- than in CARN+ animals and fell after LPS. SVR fell after LPS and was lower in CARN- than in CARN+ piglets. LPS-treated animals transiently increased urinary flow. By all measures (plasma tumor necrosis factor alpha, glucose and lactate, tissue nitric oxide, and urinary nitrite excretion), LPS provocation was similar for both groups. Chronologically, BP changes were more closely related to SVR than to CO. Our findings suggest that carnitine deprivation diminishes tissue carnitine concentrations and adversely affects cardiovascular response to LPS, in part mediated by the peripheral vasculature.
Penn
D
D
Department of Pediatrics, Louisiana State University Medical Center, New Orleans 70112, USA.
Zhang
L
L
Bobrowski
P J
PJ
Quinn
M
M
Liu
X
X
McDonough
K H
KH
D000758:Anesthesia; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002302:Cardiac Output / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002331:Carnitine / Q000097:blood / Q000172:deficiency*; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D009569:Nitric Oxide / Q000032:analysis; D009573:Nitrites / Q000652:urine; D010288:Parenteral Nutrition; D018805:Sepsis / Q000503:physiopathology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014554:Urination / Q000187:drug effects
D001786:Blood Glucose; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019344:Lactic Acid; D002331:Carnitine