[Electrophysiologic effects of K+ and Mg2+ in the hypoxia model].
The influence of Mg2+ and K+ on reoxygenation arrhythmias following 18 min of hypoxia (pO2 about 1 mm Hg, no glucose, 10 mmol/l2-desoxyglucose) has been investigated in isolated guinea-pig left atria (stimulation rate 1 Hz). Duration of reoxygenation arrhythmias was slightly reduced by increase in Mg2+ (0.6 to 4.8 mmol/l) and enhanced by decrease in Mg2+ (0.1 mmol/l), however, this effect was not significantly different from control (0.6 mmol/l). In contrast, low K+ (< 4 mmol/l) led to a significant (p < or = 0.05) prolongation and high K+ (> 5 mmol/l) to a significant abbreviation of reoxygenation arrhythmias. Increase in Mg2+ significantly attenuated the proarrhythmic effects of low K+ and enhanced the antiarrhythmic effects of high K+. Furthermore, the influence of Mg2+ and K+ on action potential parameters has been investigated in hypoxic guinea-pig papillary muscles (pO2 65 to 75 mm Hg). Action potential duration at 30% (APD30) and 90% repolarization (APD90) were increased by both electrolytes whereas resting potential, amplitude of the action potential and maximum upstroke velocity were not changed with the exception of a depolarization induced by elevated K+. 1 mmol/l Mg2+ increased APD30 to 145 +/- 16% (n = 6, p < 0.05) and APD90 to 117 +/- 9% (n = 6, p > 0.05) of control (0.6 mmol/l Mg2+). Increase of K+ from 2 mmol/l (control) to 4.7 mmol/l increased APD30 to 188 +/- 13% (n = 6, p < 0.05) and APD90 to 136 +/- 13% (n = 6, p < 0.05). The delay in repolarization observed already in therapeutic concentrations showed no inverse use dependence as it was not attenuated if stimulation rate was increased from 0.17 to 1 Hz which is in contrast to the effects of class 3 antiarrhythmic drugs (for example sotalol). Increase in concentration of both electrolytes led to an additive increase in action potential duration. Mg2+ (0.6 to 4.8 mmol/l) suppressed late afterdepolarizations and -contractions in K(+)-depolarized guinea-pig papillary muscles (27 mmol/l K+, 0.5 mmol/l Ba2+) induced by 2 x 10(-8) mol/l isoprenaline. The change in the triphasic contraction cycle by elevation of Mg2+ indicates that Mg2+ additionally increases stimulus-induced release of Ca2+ from the sarcoplasmic reticulum and reduces slow Ca2+ inward current. The described electrophysiological actions of the electrolytes represent mechanisms, which may explain their antiarrhythmic actions observed in clinical studies.
Borchard
U
U
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf.
Berger
F
F
Hafner
D
D
Hermsen
D
D
Picker
O
O
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D008274:Magnesium / Q000494:pharmacology* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009924:Organ Culture Techniques; D011188:Potassium / Q000494:pharmacology* / Q000502:physiology; D012815:Signal Processing, Computer-Assisted
D008274:Magnesium; D011188:Potassium