Hemodynamic effects of S-nitrosocysteine, an intravenous regional vasodilator

Background: S-nitrosocysteine is a carrier form of nitric oxide that can be delivered intravenously. S-nitrosocysteine is rapidly metabolized by plasm a (half-life = 2-3 seconds), forming nitric oxide and cysteine. With its sh ort half-life and potent vasodilatory properties, S-nitrosocysteine may be useful as a pulmonary vasodilating agent in cases of postoperative and chro nic pulmonary hypertension. Objective: Our objective was to determine the hemodynamic properties of S-n itrosocysteine on the pulmonary and systemic circulations to assess its pot ential utility as a pulmonary vasodilatory agent. Methods: Eleven adult swine were anesthetized. Thermodilution (Swan-Ganz; B axter International, Inc, Deerfield, III) and arterial catheters were inser ted. Flow probes were placed around the coronary, renal, superior mesenteri c, and iliac arteries. Incremental infusion doses of S-nitrosocysteine (5-8 0 nmol . kg(-1) . min(-1)) were delivered into the right atrium. Cardiac ou tput, right and left heart pressures, heart rate, Pao(2), and iliac, renal, coronary, and mesenteric blood flow rates were recorded at baseline and at each infusion dose of S-nitrosocysteine. Results: Low-dose S-nitrosocysteine infusion decreased mean pulmonary arter y pressure (15%, P =.013) without a significant reduction in mean systemic artery pressure. Higher dose infusions produced further dose-dependent decl ines in pulmonary vascular resistance and measurable reductions in systemic vascular resistance (P =.01). At an S-nitrosocysteine dosage of 40 nmol . kg(-1) . min(-1), there was a significant reduction in renal (P <.001) and mesenteric (P =.003) blood flow but no change in iliac (P >.2) or coronary (P >.2) blood flow. Cardiac output remained constant up to infusion rates o f 40 nmol . kg(-1) . min(-1) (P >.2). Doses higher than 5 nmol . kg(-1) . m in(-1) resulted in a substantial dose-dependent reduction in Pao(2) (P <.00 1), suggesting dilation of atelectatic areas of the lung. Conclusion: S-nitrosocysteine is a potent vasodilatory agent capable of ove rcoming the hypoxic vasoconstrictive response of the lung. Our results sugg est it may prove useful as a pulmonary vasodilatory agent at low doses. Hig her dose infusions reduce mean systemic pressure and lead to compensatory r eductions in renal and mesenteric blood flow without a decrease in cardiac output.