Effect of Diabetes on Nitric Oxide Metabolism During Cardiac Surgery
- Division of Cardiac Surgery, Department of Surgery, University of Leicester, Glenfield Hospital, Leicester, United Kingdom
The metabolism of nitric oxide (NO) during cardiac surgery is unclear. We studied the effect of diabetes on NO metabolism during cardiac surgery in 40 subjects (20 with diabetes and 20 without diabetes). The patients were randomized to receive an infusion of physiological saline or nitroglycerin (GTN) at 1 μg · kg–1 · min–1 starting 10 min before the initiation of cardiopulmonary bypass and then continuing for a period of 4 h. Blood and urine samples were collected at several time points for up to 8 h. NO metabolites were determined by the measurement of nitrate/nitrite (NOx, μmol/mmol creatinine) and cyclic guanosine monophosphate (cGMP, nmol/mmol creatinine) in plasma and urine. Plasma insulin levels were also determined at selected time points. Plasma NOx levels before surgery were significantly elevated in the group with diabetes compared with the group without diabetes (P < 0.001), and values were further increased during surgery in the former (P = 0.005) but not in the latter (P = 0.8). The greater plasma NOx values in patients with diabetes were matched by commensurate elevations in plasma cGMP levels (P = 0.01). Interestingly, infusion of GTN, an NO donor, significantly reduced plasma NOx (P < 0.001) and its urine elimination (P < 0.001) in patients with diabetes without reducing plasma cGMP levels (P = 0.89). Cardiac surgery increased plasma insulin in patients with and without diabetes; this increase was delayed by the infusion of GTN, but it was not related to the changes in NO production. In conclusion, NO production during cardiac surgery is increased in patients with diabetes, and this elevation can be blunted by the infusion of GTN in a rapid and reversible manner.
Address correspondence and reprint requests to Manuel Galiñanes, MD, Division of Cardiac Surgery, Department of Surgery, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, U.K. E-mail:.
Received for publication 26 June 2000 and accepted in revised form 10 August 2001.
AUC, area under the curve; cGMP, cyclic guanosine monophosphate; CPB, cardiopulmonary bypass; GTN, nitroglycerin; NO, nitric oxide; NOS, NO synthase; NOx, nitrate/nitrite.