Nitroprusside modulates pulmonary vein arrhythmogenic activity

Background  

Pulmonary veins (PVs) are the most important sources of ectopic beats with the initiation of paroxysmal atrial fibrillation, or the foci of ectopic atrial tachycardia and focal atrial fibrillation. Elimination of nitric oxide (NO) enhances cardiac triggered activity, and NO can decrease PV arrhythmogensis through mechano-electrical feedback. However, it is not clear whether NO may have direct electrophysiological effects on PV cardiomyocytes. This study is aimed to study the effects of nitroprusside (NO donor), on the ionic currents and arrhythmogenic activity of single cardiomyocytes from the PVs.     

Repeat ablation for paroxysmal atrial fibrillation – Does adenosine play a role in predicting pulmonary vein reconnection patterns?

Background

Pulmonary vein (PV) reconduction after PV isolation (PVI) unmasked by adenosine is associated with a higher risk for paroxysmal atrial fibrillation (PAF) recurrence. It is unknown if the reconnected PVs after adenosine testing and immediate re-ablation can predict reconnection and reconnection patterns of PVs at repeat procedures. We assessed reconnection of PVs with and without dormant-conduction (DC) during the first and the repeat procedure.

Levosimendan Relaxes Pulmonary Arteries and Veins in Precision-Cut Lung Slices - The Role of KATP-Channels,cAMP and cGMP

Introduction

Levosimendan is approved for left heart failure and is also used in right heart failure to reduce right ventricular afterload. Despite the fact that pulmonary arteries (PAs) and pulmonary veins (PVs) contribute to cardiac load, their responses to levosimendan are largely unknown.

Materials and Methods

Levosimendan-induced vasorelaxation of PAs and PVs was studied in precision-cut lung slices from guinea pigs by videomicroscopy; baseline luminal area was defined as 100%. Intracellular cAMP- and cGMP-levels were measured by ELISA and NO end products were determined by the Griess reaction.

Results

Levosimendan relaxed control PVs (116%) and those pre-constricted with an endothelin_A-receptor agonist (119%). PAs were only relaxed if pre-constricted (115%). Inhibition of K_ATP-channels (glibenclamide), adenyl cyclase (SQ 22536) and protein kinase G (KT 5823) largely attenuated the levosimendan-induced relaxation in control PVs, as well as in pre-constricted PAs and PVs. Inhibition of BK_Ca ²⁺-channels (iberiotoxin) and K_v-channels (4-aminopyridine) only contributed to the relaxant effect of levosimendan in pre-constricted PAs. In both PAs and PVs, levosimendan increased intracellular cAMP- and cGMP-levels, whereas NO end products remained unchanged. Notably, basal NO-levels were higher in PVs. The K_ATP-channel activator levcromakalim relaxed PAs dependent on cAMP/PKA/PKG and increased cAMP-levels in PAs.

Discussion

Levosimendan initiates complex and divergent signaling pathways in PAs and PVs. Levosimendan relaxes PAs and PVs primarily via K_ATP-channels and cAMP/cGMP; in PAs, BK_Ca ²⁺- and K_v-channels are also involved. Our findings with levcromakalim do further suggest that in PAs the activation of K_ATP-channels leads to the production of cAMP/PKA/PKG. In conclusion, these results suggest that levosimendan might reduce right ventricular afterload by relaxation of PAs as well as pulmonary hydrostatic pressure and pulmonary edema by relaxation of PVs.