Effects of components of ischemia and metabolic inhibition on delayed afterdepolarizations in guinea pig papillary muscle.
Delayed afterdepolarizations (DADs) may develop into triggered automaticity and ventricular arrhythmias. However, the potential role of DADs in the genesis of ischemic arrhythmias is not clear. We studied the effects of different components of severe ischemia (acidosis, hypoxia, lactate, increased potassium, and the absence of glucose) on DADs. DADs were evoked using trains of 30-60 externally applied pulses at a rate of 4-5 Hz in the presence of isoproterenol (10(-7) M) or dibutyryl cyclic 3', 5' adenosine monophosphate (dB-cAMP, 10(-3) M). Acidosis, caused by the addition of protons (pH = 6.8), increased the amplitude of DADs from 3.2 +/- 0.4 to 5.9 +/- 0.5 mV (n = 8, p less than 0.001). DADs were abolished by hypoxia (pO2 less than 35 mm Hg, n = 7, p less than 0.001) from control values of 3.4 +/- 0.3 mV. DADs were also abolished by neutral lactate (20 mM, n = 7, p less than 0.001) in the absence of glucose. Acidotic lactate (20 mM, pH0 = 6.8), however, was unable to abolish DADs. Increasing the extracellular potassium concentration to 16.2 mM decreased DAD amplitude from 3.6 +/- 0.27 mV to 1.3 +/- 0.1 mV (n = 5, p less than 0.002) with an associated reduction of membrane potential from -86.2 +/- 0.9 to -58.6 +/- 0.9 mV. The overall effect of simulated ischemia (all components tested together) was to abolish DADs (n = 8, p less than 0.001), with hypoxia as the most important factor.(ABSTRACT TRUNCATED AT 250 WORDS)
D000138:Acidosis / Q000503:physiopathology; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D003486:Cyanides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology*; D011188:Potassium / Q000494:pharmacology
D003486:Cyanides; D007461:Iodoacetates; D007773:Lactates; D019344:Lactic Acid; D003847:Deoxyglucose; D011188:Potassium; D019807:Iodoacetic Acid