Systemic Blockage of Nitric Oxide Synthase by L-NAME Increases Left Ventricular Systolic Pressure, Which Is Not Augmented Further by Intralipid.

Abstract

Intravenous lipid emulsions (LEs) are effective in the treatment of toxicity associated with various drugs such as local anesthetics and other lipid soluble agents. The goals of this study were to examine the effect of LE on left ventricular hemodynamic variables and systemic blood pressure in an in vivo rat model, and to determine the associated cellular mechanism with a particular focus on nitric oxide. Two LEs (Intralipid (R) 20% and Lipofundin (R) MCT/LCT 20%) or normal saline were administered intravenously in an in vivo rat model following induction of anesthesia by intramuscular injection of tiletamine/zolazepam and xylazine. Left ventricular systolic pressure (LVSP), blood pressure, heart rate, maximum rate of intraventricular pressure increase, and maximum rate of intraventricular pressure decrease were measured before and after intravenous administration of various doses of LEs or normal saline to an in vivo rat with or without pretreatment with the non-specific nitric oxide synthase inhibitor N-omega-nitro-L-arginine-methyl ester (L-NAME). Administration of Intralipid (R) (3 and 10 ml/kg) increased LVSP and decreased heart rate. Pretreatment with L-NAME (10 mg/kg) increased LSVP and decreased heart rate, whereas subsequent treatment with Intralipid (R) did not significantly alter LVSP. Intralipid (R) (10 ml/kg) increased mean blood pressure and decreased heart rate. The increase in LVSP induced by Lipofundin (R) MCT/LCT was greater than that induced by Intralipid (R). Intralipid (R) (1%) did not significantly alter nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-denuded rat aorta. Taken together, systemic blockage of nitric oxide synthase by L-NAME increases LVSP, which is not augmented further by intralipid (R).