Mechanism of reduction of action potential duration of ventricular myocardium by exogenous lactate.
Shortening of the action potential duration and the attendant reduction of refractory period in regional myocardial ischaemia might set the stage for the genesis and re-entry of ectopic impulses. We investigated the mechanism by which neutral lactate shortens the action potential duration since lactate accumulates highest in regions where coronary flow is lowest after experimental coronary artery occlusion. In preliminary experiments (unpublished) when 10 mM of L(+)-Na lactate was substituted for glucose (10 mM), action potential duration shortened in the majority of guinea pig papillary muscles. In some of the muscles, the action potential duration lengthened. When the perfusate contained neither glucose nor lactate (i.e. substrate free) action potential duration shortened in the majority of experiments. As mechanism, we supposed that the relatively high contraction rate of the preparations (120/min) could exhaust glycogen stores thereby limiting glycolysis and shortening the action potential duration. Thus variable action potential duration during lactate or substrate-free superfusion, might be explained by a corresponding variability of pre-existing glycogen stores. Therefore, in the present study we attempted to reduce the demand on glycogen stores by decreasing the contraction rate to 30/min. In the latter preparation, when the diastolic (passive) tension was completely normal, lactate (10 mM) shortened the action potential duration by 30%, whereas the action potential duration was not altered during substrate free superfusion. We then explored the possibility that lactate shortened the action potential duration by inhibition of glycolysis. First, muscles were made to perform external work by increasing passive tension to the peak of the active length-tension curve.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology; D003847:Deoxyglucose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006168:Guinea Pigs; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008353:Mannitol / Q000494:pharmacology; D010210:Papillary Muscles / Q000502:physiology*
D007773:Lactates; D019344:Lactic Acid; D008353:Mannitol; D006003:Glycogen; D003847:Deoxyglucose; D005947:Glucose