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 ( 31 P 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/dt max ), 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 vivo 31 P 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.