Magnitude and time course of extracellular potassium inhomogeneities during acute ischemia in pigs : effect of verapamil

Prior studies have demonstrated the presence of inhomogeneities in myocardial [K+]e after serial 10-minute occlusions of the left anterior descending coronary artery in the pig, even within restricted locations of an ischemic zone. These inhomogeneities are thought to underlie the electrophysiological abnormalities responsible for lethal ventricular arrhythmias through reentrant and nonreentrant pathways, but a clear association has not been demonstrated. As a prerequisite to establishing this association, these studies were performed to establish measurement standards for [K+]e inhomogeneity, to quantify the magnitude and time course of these inhomogeneities, to determine whether the inhomogeneities are greater in the ischemic border where lethal ventricular arrhythmias are known to originate, and to assess the effect of a known antifibrillatory drug on [K+]e inhomogeneities. [K+]e (expressed as the change in potassium equilibrium potential, dEK [mV]) was measured in 15 preparations using an average of 17 closely spaced, critically calibrated K(+)-sensitive electrodes having stable response characteristics. A series of four 10-minute occlusions each separated by a 50-minute reperfusion period were performed in each study. In half of the studies, intravenous verapamil (0.2 mg/kg bolus followed by 0.0065 mg/kg/hr) was administered before the fourth occlusion. In nine studies (five control and four verapamil), electrodes were placed in the marginal ischemic zone (from 2 mm outside to 5 mm inside the visible cyanotic border). In six other studies (three control and three verapamil), electrodes were placed in the central ischemic zone (10-20 mm within the ischemic region). We determined that the standard deviation is the best measure of inhomogeneity and that 12 equivalent measurement sites are required to estimate it with a satisfactory degree of statistical confidence. We found that after 10 minutes of ischemia, mean dEK was 1.6 times greater in the central than in the marginal ischemic zone, whereas mean standard deviation at the same time was 1.5 times greater in the marginal than in the central ischemic zone. Verapamil reduced mean dEK and mean standard deviation in both ischemic zones for most of the occlusion by delaying the rise in [K+]e and the inhomogeneity of that rise by 3-5 minutes. Comparisons of mean dEK with mean standard deviation revealed a steep linear relation in the marginal zone and a curvilinear relation in the central zone where higher