0051: Lipid emulsions used in parenteral nutrition induce endothelial dysfunction in porcine coronary artery rings: role of oxidative stress and cyclooxygenase-derived vasoconstrictors

Abstract

Lipid emulsions are used to provide a source of calories and essential fatty acids for patients requiring parenteral nutrition. They have been associated with hypertriglyceridemia, hypercholesterolemia and metabolic stress, which may promote the development of endothelial dysfunction. The aim of the present study was to determine the possibility that five different commercial lipid emulsions affect the endothelial function of coronary arteries, and, if so, to investigate the underlying mechanism. Porcine coronary arteries were incubated with lipid emulsions for 30 minutes before the determination of vascular reactivity in organ chambers and the level of oxidative stress using the redox-sensitive fluorescent dye dihydroethidium (DHE). Incubation of coronary artery rings with either Lipidem ® , Medialipid ® or Smoflipid ® (medium-chain triglycerides), but not with Intralipid ® or Clinoleic ® (long-chain triglycerides), significantly reduced the bradykinin- induced endothelium-dependent relaxations mediated by both nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH). In contrast, Lipidem ® did not affect endothelium-independent relaxations to sodium nitroprusside. The endothelial dysfunction induced by Lipidem ® was significantly improved by indomethacin, a cyclooxygenase (COX) inhibitor, and by inhibitors of oxidative stress (N-acetylcysteine, superoxide dismutase, catalase) and transition metal chelating agents (neocuproine, L-histidine, desferoxamine). Lipidem ® markedly increased the vascular oxidative stress as indicated by increased DHE signal throughout the arterial wall. The present findings indicate that several but not all lipid emulsions induce an endothelial dysfunction in coronary artery rings, involving both blunted NO- and EDH-mediated relaxations. The Lipidem ® -induced endothelial dysfunction is associated with increased vascular oxidative stress and the formation of COX-derived vasoconstrictor prostanoids.