Heterogeneities in [K + ] o and TQ Potential and the Inducibility of Ventricular Fibrillation During Acute Regional Ischemia in the Isolated Perfused Porcine Heart

Abstract

Background The relation between the inducibility of ventricular fibrillation (VF) and heterogeneity of the extracellular potassium concentration ([K + ] o ) and of TQ potential is unknown. Methods and Results Data from 78 epicardial DC electrodes or from up to 32 intramural K + electrodes were acquired simultaneously. Induction of VF was attempted with one or two ventricular premature beats induced in normal myocardium in isolated porcine hearts during (1) regional perfusion of the left anterior descending artery (LAD) with a normoxic, hyperkalemic solution ([K + ] 6 to 19.6 mmol/L), (2) simulated ischemia, ie, LAD perfusion with a glucose-free, hypoxic solution ([K + ] 4 to 16 mmol/L, P o 2 <5 mm Hg, pH 6.98), and (3) regional ischemia produced by stopping LAD flow. During normoxic, hyperkalemic LAD perfusion, no VF could be induced (12 interventions, 7 hearts). During simulated ischemia (27 interventions), VF could be induced only when [K + ] o was between 8 and 13.5 mmol/L. After 5 minutes of true regional ischemia, more sites with [K + ] o between 8 and 13.5 mmol/L were present than after 10 minutes. VF could be induced with 1 ventricular premature beat in 11 of 17 interventions after 5 minutes and in 0 of 14 interventions after 10 minutes of ischemia ( P <.001). Regional simulated ischemia presents a relatively homogeneous condition compared with 5 minutes of regional ischemia (SD±SEM of TQ potential in LAD tissue, 0.9±0.05 versus 2.1±0.13 mV, respectively). True ischemia superimposed on regional simulated ischemia caused the rapid development of heterogeneities in [K + ] o and TQ potential and caused VF after 45±7 seconds in all interventions. Activation maps of induction of VF suggest a different mechanism of unidirectional block during simulated ischemia from that in true ischemia. Conclusions (1) In the presence of hypoxia and acidosis, [K + ] o between 8 and 13.5 mmol/L provides the conditions necessary for the induction of VF; (2) after 5 minutes of ischemia, these conditions are present in a larger area and inducibility of VF is higher than after 10 minutes of ischemia; and (3) small heterogeneities within the intermediate K + –concentration domain (8 to 13.5 mmol/L) are associated with high inducibility of VF.