Penn D, Zhang L, Bobrowski P J, Quinn M, McDonough K H
Department of Pediatrics, Louisiana State University Medical Center, New Orleans 70112, USA.
Shock. 1999 Feb;11(2):120-6. doi: 10.1097/00024382-199902000-00009.
Sepsis and hypoxia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine and develop low carnitine plasma and tissue levels. Because of its high metabolic 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 performance under stress, 23 neonatal piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN -) or supplemented (CARN +) with L-carnitine (400 mg/L). Bacterial endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or saline vehicle was administered to anesthetized piglets 3 h prior to study of isolated perfused hearts. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure, and left ventricular developed pressure (LVDP) were measured in vitro under aerobic, hypoxic, and reoxygenation conditions in all animals. Plasma and tissue carnitine values were lower in CARN - than in CARN + piglets. In hearts from LPS-treated animals prior to hypoxia, there was no difference in ventricular compliance between CARN - and CARN + groups. LVSP and LVDP were lower in CARN - than CARN + hearts. During hypoxia, LVSP and LVDP fell, but left ventricular end diastolic pressure increased in hearts from both LPS- and saline- treated piglets. Reoxygenation led to poorer recovery in CARN - than CARN + hearts from LPS-treated animals, but not from saline controls. During hypoxia/reoxygenation, lactate efflux initially rose and then fell, while carnitine efflux increased continually. Acetyl- and medium-chain acylcarnitines were detected in the coronary effluent. Our findings suggest that carnitine deprivation diminishes heart carnitine concentrations and impairs cardiac recovery from combined endotoxic and hypoxic stress. Possible mechanisms include reduced acyl buffering and/or impaired transport of fatty acyl groups into mitochondria.
脓毒症和缺氧是新生儿重要的应激源。接受全胃肠外营养的新生儿常规缺乏肉碱，导致血浆和组织中的肉碱水平降低。由于新生儿代谢率高且依赖脂肪酸供能，面对肉碱供应不足时，其心脏可能特别容易受到应激影响。为了研究肉碱缺乏在应激状态下是否会影响心脏功能，23只新生仔猪接受了2 - 3周的胃肠外营养，一组为无肉碱的（CARN -），另一组补充了L - 肉碱（400 mg/L，CARN +）。在对离体灌注心脏进行研究前3小时，给麻醉的仔猪静脉注射细菌内毒素（脂多糖（LPS），250 μg/kg静脉推注）或生理盐水。在有氧、缺氧和复氧条件下，对所有动物的离体心脏测量左心室收缩压（LVSP）、左心室舒张末期压力和左心室压力增量（LVDP）。CARN - 组仔猪的血浆和组织肉碱值低于CARN + 组。在缺氧前接受LPS处理的动物心脏中，CARN - 组和CARN + 组之间的心室顺应性没有差异。CARN - 组心脏的LVSP和LVDP低于CARN + 组。在缺氧期间，LPS处理和生理盐水处理仔猪的心脏中，LVSP和LVDP下降，但左心室舒张末期压力升高。复氧后，LPS处理动物的CARN - 组心脏比CARN + 组恢复得更差，但生理盐水对照组则无此差异。在缺氧/复氧期间，乳酸流出量先升高后下降，而肉碱流出量持续增加。在冠脉流出液中检测到了乙酰肉碱和中链酰基肉碱。我们的研究结果表明，肉碱缺乏会降低心脏肉碱浓度，并损害心脏从内毒素和缺氧联合应激中的恢复能力。可能的机制包括酰基缓冲减少和/或脂肪酸酰基转运到线粒体受损。
