Effects of alcohol on intracellular pH regulators and electromechanical parameters in human myocardium.
BACKGROUND
Disturbances in intracellular pH (pHi) of the heart can trigger major changes in the strength and rhythm of the heartbeat. It is well known that two extruders, Na+/H+ exchange (NHE) and Na+/HCO3- symporter (NHS), and a monocarboxylic acid transporter (MCT) are involved in acid-equivalent extruding in the human heart. Drinking alcohol has been proven to affect blood pressure and heart contractility and, sometimes, causes cardiac arrhythmia. To assess the effects of alcohol on pHi regulators and electromechanical parameters, various concentrations of alcohol were superfused into human myocardium in the present study.


METHODS
Human atrial myocardium was obtained from hearts of patients undergoing corrective cardiac surgery. Institutional rules for the protection of human subjects were observed. In the whole study, pHi was measured by an epifluorescent, ratiometric microspectrofluorimetry technique with the dye BCECF, while electrophysiological experiments were performed by traditional micropipette. NHE and NHS activities were measured after pHi recovery from intracellular acidosis induced by NH4Cl prepulse, while MCT activity was measured by a lactate adding/removing technique.


RESULTS
In pHi experiments, we demonstrated that alcohol could induce a biphasic, concentration-dependent (30-1000 mM) pHi change (i.e., alkalosis after acidosis) in human atrium in HEPES-buffered Tyrode solution. To a smaller extent, similar results were found when the superfusate was replaced by HCO3- -buffered Tyrode solution. NHE activity was increased by a moderate concentration of alcohol (30 mM), while it was inhibited in a concentration-dependent manner by higher concentrations of alcohol (>100 mM). On the contrary, 30-1000 mM alcohol increased the activity of NHS in a concentration-dependent manner. Surprisingly, MCT activity was not affected by alcohol. In electromechanical experiments, we found that alcohol (30-1000 mM) had a notable concentration-dependent inhibitory effect on the contractile force, while higher concentrations of alcohol (>100 mM) decreased the action potential amplitude, upstroke velocity, duration of repolarization, and force of contractions in a concentration-dependent way. All these alcohol-induced pHi changes and electromechanical inhibitions were reversible.


CONCLUSIONS
To our knowledge, this study provides the first evidence that alcohol can affect pHi in human myocardial tissue by changing the activity of acid extruders (i.e., NHE and NHS).
Tsai
Chien-Sung
CS
Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical Center, Neihu, Taipei, Taiwan, Republic of China. sung1500@ndmctsgh.edu.tw
Loh
Shih-Hurng
SH
Jin
Jong-Shiaw
JS
Hong
Guo-Jieng
GJ
Lin
Hei-Ting
HT
Chiung
Cheng-Shian
CS
Chang
Chung-Yi
CY
D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000138:Acidosis / Q000139:chemically induced* / Q000378:metabolism; D001696:Biomechanical Phenomena; D002021:Buffers; D027682:Cation Transport Proteins / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000378:metabolism; D008839:Microelectrodes; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D012996:Solutions; D013050:Spectrometry, Fluorescence
D002021:Buffers; D027682:Cation Transport Proteins; D002492:Central Nervous System Depressants; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; C490998:SLC9A1 protein, human; D027982:Sodium-Bicarbonate Symporters; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D012996:Solutions; D000431:Ethanol