Effects of L-NMMA and fluid loading on TNF-induced cardiovascular dysfunction in dogs.

We investigated the effects of Nω-monomethyl-l-arginine (l-NMMA) and fluid loading on tumor necrosis factor (TNF)-induced cardiovascular dysfunction in awake dogs. l-NMMA (40 mg · kg− 1 given intravenously over a period of 10 min, and followed by dosing at 40 mg · kg− 1 · h− 1 for 6 h) and TNF (20 or 45 μ g · kg− 1 given intravenously for 20 min), given alone or in combination, significantly decreased stroke volume, cardiac index, oxygen delivery, and left-ventricular (LV) function plots over a period of 6 h. Of note was that the cardiac-depressant effects of TNF and l-NMMA given together were significantly less than additive. Thus, the combination was beneficial (or significantly less harmful to cardiac performance than expected), possibly because l-NMMA augmented cardiac preload as shown by significant increases in both pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP). Fluid challenges at 6 h (Ringer's solution at 80 ml · kg− 1 given over a period of 30 min) also significantly...