title: Sex differences in the electrophysiological characteristics of pulmonary veins and left atrium and their clinical implication in atrial fibrillation.
abstract: BACKGROUND
  Sex and the autonomic nervous system play critical roles in the pathophysiology of atrial fibrillation (AF). Sex differences in electrophysiological characteristics of the pulmonary veins (PVs, AF initiator) and left atrium (LA, AF substrate) are not clear.
  
  
  RESULTS
  Conventional microelectrodes were used to record the action potential in isolated PV and LA tissue preparations from male and female (age, 8≈10 months) rabbits before and after drug administration (adenosine, acetylcholine, and isoproterenol). Male PVs (n = 7) had a higher spontaneous beating rate (1.7 ± 0.2 versus 1.2 ± 0.1 Hz, P = 0.021) and incidence of burst firing (72% versus 11%, P = 0.038) than female PVs (n = 9). Male PVs without spontaneous activity (n = 10) and the LA (n = 11) had longer action potential durations than female PVs (n = 9) and LA (n = 9). Additionally, male PVs had a more-positive resting membrane potential (79 ± 3 versus 84±2 mV, P=0.022). Isoproterenol (3 μmol/L) increased the delayed afterdepolarizations to a greater extent in male than in female PVs. In PVs without spontaneous activity or LA, isoproterenol (0.1 and 3 μmol/L) consistently shortened the action potential durations in females but not in males. Acetylcholine (5.5 μmol/L) decreased the spontaneous activity of PVs and shortened the action potential durations in both groups. Adenosine (10 μmol/L) also similarly decreased the spontaneous activity of PVs and delayed afterdepolarizations in both groups.
  
  
  CONCLUSIONS
  There are significant sex differences in PV and LA action potential characteristics in rabbits. The higher amplitude of delayed afterdepolarizations after isoproterenol superfusion in male PVs may contribute to sex-related arrhythmogenesis.
authors.affiliation: Division of Cardiology, Tzu-Chi General Hospital, Hualien, Taipei, Taiwan.
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Tsai
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011667:Pulmonary Veins / Q000503:physiopathology*; D011817:Rabbits; D012727:Sex Characteristics; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D014665:Vasodilator Agents; D000241:Adenosine; D007545:Isoproterenol; D000109:Acetylcholine