Penn D, Zhang L, Bobrowski P J, Quinn M, Liu X, McDonough K H
Department of Pediatrics, Louisiana State University Medical Center, New Orleans 70112, USA.
Shock. 1998 Nov;10(5):377-82. doi: 10.1097/00024382-199811000-00012.
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.
脓毒症和内毒素血症是新生儿重要的应激源。接受全胃肠外营养的新生儿通常缺乏肉碱。为了研究肉碱缺乏是否会影响新生儿对内毒素的反应能力，19头新生仔猪接受了2 - 3周的胃肠外营养，其中一组不含肉碱（CARN-），另一组补充了L-肉碱（400 mg/L，CARN+）。在给麻醉的仔猪静脉注射内毒素（脂多糖（LPS），250 μg/kg静脉推注）或赋形剂后，连续3小时研究其心血管功能，即心率、血压（BP）、心输出量（CO）、全身血管阻力（SVR），以及代谢反应，即血浆葡萄糖、乳酸、肿瘤坏死因子α、组织一氧化氮和尿亚硝酸盐。CARN-组仔猪的血浆和组织肉碱值低于CARN+组。在注射LPS之前，大多数参数没有差异（CARN-组动物的舒张压和SVR较低除外）。LPS注射后收缩压、舒张压和平均血压下降，但在实验结束时恢复。CARN-组仔猪的血压最低点低于CARN+组。CARN-组动物的CO往往高于CARN+组，且LPS注射后下降。LPS注射后SVR下降，CARN-组仔猪的SVR低于CARN+组。LPS处理的动物尿流量短暂增加。从所有指标来看（血浆肿瘤坏死因子α、葡萄糖和乳酸、组织一氧化氮和尿亚硝酸盐排泄），两组对LPS激发的反应相似。按时间顺序，血压变化与SVR的关系比与CO的关系更密切。我们的研究结果表明，肉碱缺乏会降低组织肉碱浓度，并对心血管系统对LPS的反应产生不利影响，部分是由外周血管系统介导的。
