Triggered activity induced by combined mild hypoxia and acidosis in guinea-pig Purkinje fibers.
The effects of prolonged exposure to combined mild hypoxia (Po2 230 +/- 20 mmHg) and acidosis (pH: 6.8 +/- 0.05) were studied in guinea-pig left ventricular myocardium superfused in vitro. Only Purkinje fibers were impaled by microelectrodes. Triggered activity developed in depolarized Purkinje fibers after 48 +/- 9 min of exposure to hypoxic and acid conditions and was initiated either by short periods of rapid electrical driving or by the background slow Purkinje automaticity. Triggered activity occurred when a delayed afterdepolarization attained its threshold potential and terminated after a subthreshold afterdepolarization. Interaction between triggered activity and slow background automaticity was observed until 90 to 180 min of exposure to hypoxic and acid conditions. These effects were reversed by replacement in standard conditions (Po2 510 +/- 20 mmHg; pH 7.35 +/- 0.05). Norepinephrine (1 X 10(-6)M) significantly accelerated the rate of discharge of triggered foci and led to a stable sustained triggered activity. Increasing extracellular Ca2+ concentration aggravated the effects of combined mild hypoxia and acidosis and led to the occurrence of early afterdepolarizations initiating triggered activity. In addition abnormal automaticity developed in quiescent fibers without any triggering action potential. Lidocaine and verapamil suppressed the triggered activity following a subthreshold afterdepolarization. Their effects were reversed on wash-out. It is concluded that prolonged exposure to combined mild hypoxia and acidosis induces triggered activity by a basic mechanism common to other situations leading to a calcium overload and showing such behaviour.
D000138:Acidosis / Q000150:complications* / Q000503:physiopathology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D008012:Lidocaine; D014700:Verapamil; D002118:Calcium; D009638:Norepinephrine