I In nf fl lu ue en nc ce e o of f e en nd do ot th he el li ia al l n ni it tr ri ic c o ox xi id de e o on n n ne eu ur ro og ge en ni ic c c co on nt tr ra ac ct ti io on n o of f h hu um ma an n p pu ul lm mo on na ar ry y a ar rt te er ri ie es s ABSTRACT: The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients).Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10 -6 M). The increases in tension were of greater magnitude in arteries denuded of endothelium. N G -nitro-L-arginine methyl ester (L-NAME) (10 -4 M) potentiated the contractile response to EFS in artery rings with endothelium but not in endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10 -4 M) but not by D-arginine (10 -4 M). Indomethacin (3×10 -6 M) had no significant effect on the contractile response to EFS. Contractile responses to noradrenaline were similar in arteries with and without endothelium.Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide, which inhibits the contractile responses of human pulmonary arteries. Although adrenergic nerves seem to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be noradrenaline.

No abstract

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” Bachground. Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in endothelium adhesion, is an understudied area in the MVO setting. Purpose. We aimed to evaluate whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. Methods. We prospectively included 106 patients with a first STEMI treated with primary percutaneous coronary intervention, quantifying serum levels of EpCAM 24 hours post-reperfusion. All patients underwent CMR imaging 1 week and 6 months post-STEMI. The independent correlation of EpCAM with MVO, systolic volume indices, and left ventricular ejection fraction (LVEF) was evaluated. Results. The mean age of the sample was 59 ± 13 years and 76% were male. Patients were dichotomized according to EpCAM median (4.48 pg/mL). At 1-week CMR, lower EpCAM was related to extensive MVO (p-value = 0.02) and greater infarct size (p-value = 0.02). At presentation, only EpCAM values were significantly associated with the presence of MVO in univariate (Odds Ratio [95% confidence interval] (OR [95% CI]): 0.58 [0.38-0.88], p-value = 0.01) and multivariate logistic regression models (OR [95% CI]: 0.54 [0.34-0.85], p-value = 0.007). Although MVO tends to resolve at chronic phases, decreased EpCAM was associated with worse systolic function: depressed LVEF (p-value = 0.009) and higher left ventricular end-systolic volume (p-value = 0.04). Conclusions. EpCAM is associated with occurrence of CMR-derived MVO at acute phases and long-term adverse ventricular remodeling post-STEMI. Future studies are needed to confirm EpCAM as biomarker, and eventually biotarget in STEMI pathophysiology.

No abstract