Increased nitric oxide synthase activity after canine cardiopulmonary bypass is suppressed by S-nitrosoglutathione

Objectives: Hemodynamic instability and generalized organ dysfunction are c ommon after cardiopulmonary bypass in human beings. Previous studies have s uggested that alterations of nitric oxide metabolism may be associated with this impaired function. Using a canine model we tested whether nitric oxid e synthase activity is increased after cardiopulmonary bypass. We also test ed whether administration of a nitric oxide donor can influence nitric oxid e synthase activity after cardiopulmonary bypass. Methods: After induction of anesthesia, dogs were randomized to receive cardiopulmonary bypass (n = 12) or to serve as controls (n = 12), They were further randomized to recei ve a continuous infusion of a nitric oxide donor, S-nitrosoglutathione, or an equivalent volume of placebo. Cardiopulmonary bypass was maintained for 90 minutes, and then 4 hours later dogs were put to death. Cardiac and coro nary artery sections were frozen in liquid nitrogen immediately after death for later determination of nitric oxide synthase activity using a citrulli ne assay. Results: After cardiopulmonary bypass, 4 of 6 placebo-treated but only 2 of 6 S-nitrosoglutathione-treated animals required phenylephrine in fusion (3.1 +/- 3.1 mu g/min and 0.2 +/- 0.4 mu g/min, respectively P =.05) to maintain a predetermined blood pressure. Furthermore, after cardiopulmo nary bypass, Ca2+-dependent nitric oxide synthase activity in the left vent ricle, atrium, and coronary artery did not increase compared with activity in the control animals, but Ca2+-independent nitric oxide synthase activity did increase (P =.005): left ventricle (+28.0% +/- 9.0%), atrium (+45.0% /- 12.0%) and coronary artery (+17.0% +/- 12.0%), Conclusions: We have foun d that (1) cardiopulmonary bypass results in increased activity of Ca2+-ind ependent nitric oxide synthase, (2) S-nitrosoglutathione can prevent the in crease of Ca2+-independent nitric oxide synthase after cardiopulmonary bypa ss,and (3) Ca2+-independent nitric oxide synthase may contribute to hemodyn amic dysfunction after cardiopulmonary bypass.