NOS substrate during cardioplegic arrest and cold storage decreases stunning after heart transplantation in a rat model
Caus T., Desrois M., Izquierdo M., Lan C., LeFur Y., Confort-Gouny S., Métras D., Clarke K., Cozzone PJ., Bernard M.
Background: In this study, we evaluated how adding L-arginine to Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution affected myocardial performance during post-ischemic in vivo reperfusion. Methods: Experiments were conducted using a modified Lewis-Lewis heterotopic heart transplantation model, with a total ischemic time of 3 hours followed by 1 or 24 hours of blood reperfusion. Heart grafts were arrested using intra-aortic injection of CRMBM solution, either supplemented or not supplemented with 2 mmol/liter L-arginine (n = 12 in each group). We measured systolic indexes and simultaneously performed phosphorus magnetic resonance spectroscopy (31P MRS). We quantified total endothelial nitric oxide synthase (eNOS) protein using the Western blot test of freeze-clamped hearts. Results: Contractility during early reperfusion was significantly better in grafts arrested with CRMBM solution enriched with L-arginine: mean rate pressure product, 11249 ± 1,548 vs 5,637 ± 1,118 mm Hg/min (p = 0.05), and maximal first derivative of the pressure signal (dP/dtmax), 1,721 ± 177 vs 1,214 ± 321 mm Hg/sec (p = 0.013). Conversely, during late reperfusion, contractility did not relate to the nature of the preservation solution. The presence of L-arginine in the CRMBM solution did not alter time-related variations of high-energy phosphate ratios measured using in vivo31P MRS. The eNOS protein level decreased significantly during early compared with late reperfusion, with no effect caused by L-arginine. Conclusions: During early reperfusion, the limited myocardial stunning observed with CRMBM solution containing L-arginine does not relate to energy metabolism but to better preservation of the NO pathway.