We studied the time course, magnitude and homogeneity of the change in extracellular myocardial potassium activity after acute ligation of the left anterior descending coronary artery in pigs using potassium-sensitive electrodes made from a valinomycin-polyvinyl chloride matrix membrane. We also studied the relationship between the changes in potassium activity and the simultaneous changes in ventricular activation using the reference barrel of the K+ electrode to record ventricular electrograms. We found that the K+ rose sooner, more rapidly and to higher levels than previously reported. The K+ changes occurred in three phases: a phase of rapidly rising K+ that began within seconds of the ligation and lasted 5-15 minutes, a plateau phase that lasted approximately 15 minutes and a phase of slowly rising K+ that extended throughout the longest occlusion (60 minutes) used in this study. The K+ changes were reversed by release of the occlusion during the rapidly rising and plateau phases, but were not reversed by release of the occlusion during the phase of slowly rising K+. Inhomogeneities in the K+ rise appeared between the center and lateral margins of the midmyocardial ischemic zone, between the subendocardium and the subepicardium in the center of the ischemic zone, and between closely spaced electrodes located in the midmyocardial center of the ischemic zone. Thus, the change in K+ activity, as recorded by our electrodes, can be considered an excellent marker of ischemia. Changes in ventricular activation paralleled the K+ rise, the inhomogeneities of K+ rise and the reversal of the K+ rise after release but could not be entirely explained by the change in K+.

SUMMARY1. Reactivation kinetics of the rapid and slow inward currents in ventricular fibres have been assessed by studying the maximum rate of rise ((dV/dt)max) of the action potential upstroke and the duration of the plateau in progressively earlier premature responses. Reactivation of the slow inward current was also studied by voltage clamp technique in sheep and pig ventricular trabeculae.2. The time constant of recovery of (dV/dt)max was voltage dependent and increased from less than 20 msec when the resting membrane potential was more negative than -80 mV to more than 100 msec when the resting membrane potential was between -65 and -60 mV. Similar results were obtained in Purkinje fibres. These results suggest that the time constant for reactivation is slower than the time constant for inactivation of the rapid inward current system by at least one order of magnitude.3. The time constant of recovery of plateau duration was also voltage dependent and increased from 30 to 70 msec as the membrane potential was changed from -85 to -60 mV.4. The reactivation time constant of the slow inward current determined by voltage clamp experiments were similar to the results obtained by analysis of plateau duration. At potentials less negative than -60 mV the time constant of reactivation became progressively longer. Unlike reactivation time constants of (dV/dt)max, the time constants of reactivation of the slow inward current were similar to the time constants of inactivation.5. Our results indicate that (a) in premature action potentials, time as well as voltage are important determinants of (dV/dt)max in myocardial and Purkinje fibres, (b) the kinetics of reactivation of the rapid inward current in cardiac fibres are different from those in nerve and (c) plateau

An experimental approach is described to quantitate inhomogeneity in extracellular K concentration ([Ks ]out) in the presence of ischemia and to relate this inhomogeneity to the electrophysiologic changes. Extracellular potassium concentration and local direct-current electrograms from the same sites were measured in isolated perfused pig hearts with the use of multiple electrodes.Dispersion of [K' lout is described under three conditions: (1) during regional ischemia in the "central zone" and the "borderzone," (2) during global ischemia, and (3)

We studied the individual and combined effects of extracellular acidosis and increases in extracellular potassium on action potential characteristics and conduction in order to gain a better understanding of the effects of acute ischemia. At each level of potassium between 2.7 and 17 mm, acidosis induced by increasing Pco2 (respiratory acidosis) and by decreasing HCO3- (metabolic acidosis) decreased resting membrane potential, the maximum rate of rise of the action potential upstroke (Vmax), and slowed conduction. Metabolic acidosis consistently and significantly lengthened the steady state action potential duration whereas respiratory acidosis did not. Respiratory acidosis caused changes in resting membrane potential, Vmax, and conduction velocity; which occurred more rapidly and were of greater magnitude than the changes induced by metabolic acidosis. The changes in Vmax induced both types of acidosis were due to a change in the resting membrane potential-Vmax relationship as well as to the changes in the resting membrane potential. The conduction slowing induced by acidosis was greater when potassium was 9 and 13 mM than when potassium was 5.4 mm. Our results suggest that acidosis causes important changes in the electrophysiological properties of ventricular fibers and that many of the known electrophysiological effects of acute ischemia can be mimicked by the combined effects of extracellular acidosis and an increase in extracellular potassium.

For one-dimensional propagation, a nonlinear relationship between Vmax and conduction velocity is predicted by cable theory, and, under experimental conditions, Vmax and conduction velocity may change in opposite directions. Using standard microelectrode techniques, we have measured Vmax and conduction velocity in guinea pig papillary muscles exposed to tetrodotoxin and low sodium (agents expected primarily to decrease, directly, the rapid inward current), increased extracellular potassium (an agent which decreases the rapid inward current at least partially by inactivation mediated by depolarization of the resting membrane potential), and, over a wide range of stimulation frequencies, the antiarrhythmic drugs, quinidine, lidocaine, and procainamide. In all cases, except for the region of potassium-induced "supernormal conduction" between 5.4 and 9 mM, Vmax and conduction velocity varied as predicted by one-dimensional cable theory; that is, changes in Vmax were always proportional to changes in the square of conduction velocity. We conclude that the relationship between Vmax and conduction velocity predicted by cable theory occurs experimentally in guinea pig papillary muscle subjected to commonly used antiarrhythmic drugs and other interventions expected to reduce the sodium inward current. This relationship may be useful in applying known effects of drugs on Vmax to action potential propagation.