Hypoxia and reoxygenation modulate the arrhythmogenic activity of the pulmonary vein and atrium

Abstract

Ischaemia and reperfusion contribute to the genesis of AF (atrial fibrillation). PVs (pulmonary veins) and the atria are important foci for AF initiation and maintenance. However, the effect of ischaemia and reperfusion on PVs and the atria has not yet been fully elucidated. In the present study, conventional microelectrodes were used to record the APs (action potentials) in isolated rabbit PV, LA (left atrium) and RA (right atrium) specimens during hypoxia and reoxygenation, and pharmacological interventions. Hypoxia reduced the PV beating rates from 1.8±0.1 to 1.3±0.2 and 0.8±0.1 Hz at 30 and 60 min respectively (n=8, P<0.005), and induced EAD (early after depolarization) in three (37.5%) of the PVs and DAD (delayed after depolarization) in one (12.5%) of the PVs. Reoxygenation increased the PV spontaneous rate to 1.4±0.2 Hz (P<0.05) and induced PV burst firings (3.5±0.1 Hz, P<0.001) in six (75%) of the PVs. Hypoxia shortened the AP duration in the LA and PVs, but not in the RA. Pretreatment with glibenclamide attenuated hypoxia-induced decreases in the PV spontaneous activity and the shortening of the LA and PV AP duration. Similar to those in hypoxia, the K(ATP) (ATP-sensitive potassium) channel opener pinacidil (30 μM) decreased PV spontaneous activity and shortened the AP duration. Pretreatment with 5 mM N-MPG [N-(mercaptopropionyl)glycine; a hydroxyl (•OH) free-radical scavenger] or 300 μM chloramphenicol [a cytochrome P450 inhibitor that reduces ROS (reactive oxygen species)] attenuated the rate changes induced by hypoxia and reoxygenation, and also decreased the burst firing incidence. In conclusion, hypoxia and reoxygenation significantly increased PV arrhythmogenesis and induced different electrophysiological responses in the RA and LA, which may play a role in the pathophysiology of AF.

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…[304,305]. Do występowania AF u pacjentów z obturacyjnym bezdechem sennym może się przyczyniać wiele mechanizmów patofizjologicznych, w tym dysfunkcja autonomiczna, hipoksja, hiperkapnia oraz zapalenie [96,[304][305][306][307]. Obturacyjny bezdech senny nasila zmiany ciśnienia wewnątrz klatki piersiowej, które same oraz za pośrednictwem aktywacji nerwu błędnego mogą prowadzić do skrócenia potencjału czynnościowego w przedsionkach i wywoływać AF.…”

Ranolazine Attenuates the Enhanced Reverse Na+-Ca2+ Exchange Current via Inhibiting Hypoxia-Increased Late Sodium Current in Ventricular Myocytes

“…Hypoxia could do damage to cell function and induce EADs in myocardial cells (47). Previous studies showed that RAN suppressed EADs induced by many pathological conditions, such as ATXa, veratridine, and H 2 O 2 (37,48,49).…”

Acute regional left atrial ischemia causes acceleration of atrial drivers during atrial fibrillation

“…Sino et al 8 demonstrated that a 3–5-hour regional acute right atrial ischemia associates with an increased burst pacing-induced AF duration, and regional impairment in conduction. Lin et al 19 suggested that a 60-minute global atrial hypoxia leads to a shorter pulmonary vein APD and an increased number of early and delayed after-depolarizations. Also, Jayachandran et al showed that a 15-minute atrio-ventricular ischemia, obtained after right coronary ligation, leads to a right atrial APD shortening prevented by a Na/H exchanger blocker, HOE642.…”