L-Carnitine preserves endothelial function in a lamb model of increased pulmonary blood flow

Shruti Sharma, Angela Aramburo, Ruslan Rafikov, Xutong Sun, Sanjiv Kumar, Peter E. Oishi, Sanjeev A. Datar, Gary Raff, Kon Xoinis, Gohkan Kalkan, Sohrab Fratz, Jeffrey R. Fineman, Stephen M. Black

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Background: In our model of a congenital heart defect (CHD) with increased pulmonary blood flow (PBF; shunt), we have recently shown a disruption in carnitine homeostasis, associated with mitochondrial dysfunction and decreased endothelial nitric oxide synthase (eNOS)/heat shock protein (Hsp)90 interactions that contribute to eNOS uncoupling, increased superoxide levels, and decreased bioavailable nitric oxide (NO). Therefore, we undertook this study to test the hypothesis that L-carnitine therapy would maintain mitochondrial function and NO signaling. Methods: Thirteen fetal lambs underwent in utero placement of an aortopulmonary graft. Immediately after delivery, lambs received daily treatment with oral L-carnitine or its vehicle. Results: L-Carnitine-treated lambs had decreased levels of acylcarnitine and a reduced acylcarnitine:free carnitine ratio as compared with vehicle-treated shunt lambs. These changes correlated with increased carnitine acetyl transferase (CrAT) protein and enzyme activity and decreased levels of nitrated CrAT. The lactate:pyruvate ratio was also decreased in L-carnitine-treated lambs. Hsp70 protein levels were significantly decreased, and this correlated with increases in eNOS/Hsp90 interactions, NOS activity, and NOx levels, and a significant decrease in eNOS-derived superoxide. Furthermore, acetylcholine significantly decreased left pulmonary vascular resistance only in L-carnitine-treated lambs. Conclusion: L-Carnitine therapy may improve the endothelial dysfunction noted in children with CHDs and has important clinical implications that warrant further investigation.

Original languageEnglish (US)
Pages (from-to)39-47
Number of pages9
JournalPediatric Research
Issue number1
StatePublished - Jul 2013
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


Dive into the research topics of 'L-Carnitine preserves endothelial function in a lamb model of increased pulmonary blood flow'. Together they form a unique fingerprint.

Cite this