Effects of the thromboxane A2 analogue, STA2, on the transmembrane potentials of guinea pig ventricular muscles under normal and simulated ischaemic conditions.
To assess whether thromboxane A2 (TXA2) exerts a direct electrophysiological effect on cardiac muscle, the effects of STA2 (10 micrograms/l), a stable TXA2 analogue, on the action potentials were examined in isolated guinea pig ventricular muscles using conventional microelectrode techniques. STA2 failed to induce any significant changes in the action potential characteristics in both normal Tyrode's solution and the hyperkalemic (K+ = 10.8 mM) solution. 15 min of superfusion with the "ischemic" solution, which consisted of hyperkalemia (K+ = 10.8 mM), hypoxia (pO2 less than 50 mmHg), acidosis (pH = 6.4) and substrate deprivation (glucose-free), progressively shortened the action potential duration and reduced the resting membrane potential, action potential amplitude and Vmax. STA2 did not affect the changes in the action potential during such "ischemic" superfusion. These results indicate that STA2 exerts no direct electrophysiological effects on both the normal and the "ischemic" myocardium. The arrhythmogenic effects of TXA2 observed in in vivo studies might reflect the ability of TXA2 to induce platelet aggregation and vasoconstriction resulting in an exacerbation of myocardial ischemia.
2nd Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
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T
Ogura
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Watanabe
J
J
Kajita
T
T
Saito
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S
Saito
Y
Y
Ozawa
M
M
Hatano
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012996:Solutions; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D016276:Ventricular Function
D012996:Solutions; D013928:Thromboxane A2; C037866:STA 2; D011188:Potassium; D010100:Oxygen