title: Antiarrhythmic effects of dehydroevodiamine in isolated human myocardium and cardiomyocytes.
abstract: BACKGROUND
  Dehydroevodiamine alkaloid (DeHE), a bioactive component of the Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), exerted antiarrhythmic effect in guinea-pig ventricular myocytes. We further characterize the electromechanical effects of DeHE in the human atrial and ventricular tissues obtained from hearts of patients undergoing corrective cardiac surgery or heart transplantation.
  
  
  METHODS
  The transmembrane potentials of human myocardia were recorded with a traditional microelectrode technique while sarcolemmal Na(+) and Ca(2+) currents in single human cardiomyocytes were measured by a whole-cell patch-clamp technique. The intracellular pH (pHi) and Na(+)-H(+) exchanger (NHE) activity were determined using BCECF-fluorescence in human atria.
  
  
  RESULTS
  In human atria, DeHE (0.1-0.3 μM) depressed upstroke velocity, amplitude of action potential, and contractile force, both in slow and fast response action potential. Moreover, the similar depressant effects of DeHE were found in human ventricular myocardium. Both in isolated human atrial and ventricular myocytes, DeHE (0.1-1 μM) reversibly, concentration-dependently decreased the Na(+) and Ca(2+)currents. Moreover, DeHE (0.1 and 0.3 μM) suppressed delayed afterdepolarizations and aftercontractions, induced by epinephrine and high [Ca(2+)]o in atria. In human ventricular myocardium, the strophanthidin-induced triggered activities were attenuated by pretreating DeHE (0.3 μM). The resting pHi and NHE activity were also significantly increased by DeHE (0.1-0.3 μM).
  
  
  CONCLUSIONS
  We concluded for the first time that, in the human hearts, DeHE could antagonize triggered arrhythmias induced by cardiotonic agents through a general reduction of the Na(+) and Ca(2+) inward currents, while increase of resting pHi and NHE activity.
authors.affiliation: Department of Pharmacology, Tri-Service General Hospital, National Defense Medical Center, No. 161, Ming-Chuan E. Rd., Sect. 6, Nei-Hu District, Taipei 114, Taiwan, ROC. Electronic address: shloh@ndmctsgh.edu.tw.
authors.forename: Shih-Hurng
authors.initials: SH
authors.lastname: Loh
authors.affiliation: Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Tsai
authors.affiliation: Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of General Surgery, Cheng-Hsieng General Hospital, Taipei 114, Taiwan, ROC.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC.
authors.forename: Chien-Sung
authors.initials: CS
authors.lastname: Tsai
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 420, Taiwan, ROC.
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.affiliation: Department of Physiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC.
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Lin
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000502:physiology
chemical_list: D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; C028633:dehydroevodiamine; D012964:Sodium; D002118:Calcium
keywords: Action potential and ionic currents; BCECF-AM (PubChem CID: 53229972); Dehydroevodiamine; Dehydroevodiamine chloride (PubChem CID: 156371); Epinephrine (PubChem CID: 5816); Human cardiomyocytes; Intracellular pH; NH(4)Cl (PubChem CID: 25517); Na(+)–H(+) exchanger; Nigericin (PubChem CID: 34230); Strophanthidin (PubChem CID: 6185); Whole-cell patch-clamp