Shih-Hurng Loh1, Yi-Ting Tsai2, Chung-Yi Lee2, Chung-Yi Chang3, Chien-Sung Tsai2, Tzu-Hurng Cheng4, Cheng-I Lin5. 1. 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. 2. Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC. 3. Department of General Surgery, Cheng-Hsieng General Hospital, Taipei 114, Taiwan, ROC. 4. Department of Biological Science and Technology, China Medical University, Taichung 420, Taiwan, ROC. 5. Department of Physiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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.
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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 humanventricular 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 humanventricular 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.