Abstract
Uncoupled endothelial nitric oxide synthase (eNOS) is a major contributor to vascular reactive oxygen species generation in ischaemia/reperfusion (I/R) injury. Supplementation of NO by the novel NO donor S-nitroso human serum albumin (S-NO-HSA) may inhibit uncoupling of eNOS (feedback inhibition). Pigs (n = 14; 33.1 +/- 1.7 kg) were continuously monitored for heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and coronary flow (CF). Infusion of either human serum albumin (n = 8; controls) or S-NO-HSA (n = 6) lasted 60 min (0.1 micromol/kg/h) starting 15 min prior to ischaemia. After clamping the aorta under cardiopulmonary bypass (CPB), the hearts underwent 15 min of warm, unprotected ischaemia (37 degrees C). Reperfusion lasted 150 min (30 min under CPB; 15 min weaning; additional 105 min reperfusion). In biopsies from non-ischaemic hearts and myocardial biopsies taken after 150 min of reperfusion, high-energy phosphates were measured and the calcium ionophore-stimulated release of NO, superoxide, and peroxynitrite (ONOO(-)) were monitored with nanosensors. Compared with non-ischaemic hearts, the NO level decreased from 930 +/- 25 to 600 +/- 15 nmol/L (P < 0.001) while the superoxide level increased from 45 +/- 5 to 110 +/- 10 nmol/L (P < 0.001) after ischaemia. S-NO-HSA restored the NO level to 825 +/- 20 nmol/L, shifted favourably the [NO]/[ONOO(-)] balance (a marker of eNOS uncoupling) from 1.36 +/- 0.06 (ischaemia) to 3.59 +/- 0.18, significantly improved CF (65 +/- 10 vs. control, 43 +/- 5 mL/min, P < 0.05), MAP (57 +/- 5 vs. 39 +/- 3 mm Hg, P < 0.01), LVSP (106 +/- 5 vs. 81 +/- 4 mm Hg, P < 0.01) and phosphocreatine (PCr) content (41.5 +/- 7.3 vs. 18.0 +/- 5.6 micromol/g protein; P < 0.01) at 150 min of reperfusion. Long-lasting release of NO by S-NO-HSA prevented uncoupling of eNOS and thereby improved systolic and diastolic function, myocardial perfusion, and the energetic reserve of the heart after I/R injury.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
