Fabrication, evaluation, and use of extracellular K+ and H+ ion-selective electrodes.

Ion-selective mini-electrodes have been widely employed to measure extracellular K+ and H+ during myocardial ischemia. However, the recent availability of this technology has not been accompanied by uniform fabrication, amplification, and calibration standards. In their fabrication, the chloride tips of Teflon-coated silver wires should be covered with a cellulose acetate-titanium dioxide sponge followed by a polyvinyl chloride (PVC)-valinomycin (K+) or PVC-tridodecylamine (H+) ion-selective membrane. Critical analysis of the nonworking electrodes using scanning electron micrographs has revealed membrane holes, membrane and sponge contamination, Teflon plaque, poor membrane-sponge-Teflon adhesion, and improperly applied or torn membrane. We have also found that signal amplification must have variable-gain filtration (0-1 Hz) with 0.5-pA input offset current and 10(12)-omega input resistance. Furthermore, in vitro calibration in 3 and 10 mM KCl (K+) or pH 8 and 6 buffer (H+) should produce a Nernstian slope +/- 5 or 10%, respectively, at 26 degrees C with a response time less than or equal to 50 ms, resistance greater than or equal to 10(12) omega, and drifts less than or equal to 1 mV/h. In vivo performance and calibration criteria (delineated for K+ only) include 1) transient response to bolus injections of KCl (0.12 mM/kg body wt) yielding peak amplitude changes of 2.5-3.0 mM, response times less than or equal to 10 s, and washout time constants less than or equal to 3 min, and 2) in vivo calibration to artificial independently confirmed systemic [K+] producing a Nernstian slope +/- 15% at 38 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between extracellular potassium accumulation and local TQ-segment potential during acute myocardial ischemia in the porcine.

Depolarization of resting membrane potential during acute myocardial ischemia is strongly correlated with the accumulation of extracellular potassium ([K+]e). Also, diastolic currents of injury flowing across the ischemic border that occur as a result of local differences in resting membrane potentials cause changes in the TQ-segments of unipolar, DC-coupled, extracellular electrograms. Further, the changes in [K+]e and TQ-segment potentials during acute ischemia and reperfusion follow a similar time course. For these reasons, a predictable relationship between [K+]e and TQ potentials might be expected to exist. If found, easily obtainable local TQ potential measurements could serve as an index of the resting membrane depolarization induced by [K+]e accumulation and, by extension, as an index of ischemic injury. We measured local [K+]e and TQ potentials from 30 mid-myocardial sites in central and marginal ischemic zones in 2 isolated, Langendorff-perfused porcine hearts during a single, 10-min ligation of the left anterior descending coronary artery. In general, we found a linear relationship between [K+]e and TQ potential for both ischemic zones when data was taken as a whole, but the slopes (S) and correlation coefficients (R) were markedly different between the two locations (-2.24 vs -1.28 and -0.73 vs -0.51 for central and marginal zones, respectively). Further, we found a time dependent change in both S and R that was biphasic. Both were low during the first minutes, attained their maximum values at 4 mins, and then fell during the remainder of the occlusion. We conclude, therefore, that local TQ potentials cannot be used as an index of the severity of ischemic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of verapamil on ischemia-induced changes in extracellular K+, pH, and local activation in the pig.

In experimental animals, the calcium channel-blocking agents lessen the arrhythmogenic, ionic, metabolic, and electrical changes that occur during acute myocardial ischemia. To date, these effects have been studied separately, and the effects of these agents on local activation have not been correlated with ionic or metabolic effects. In open-chest, anesthetized swine, we used bipolar and ion-selective plunge electrodes to simultaneously measure ischemia-induced changes in left ventricular local activation, extracellular K+ ([K+]e), and extracellular pH (pHe). The effects of verapamil (0.2 mg/kg) on these variables were studied during a series of 10 min occlusions of the left anterior descending coronary artery. Compared with control occlusions, verapamil (1) slowed the rise in [K+]e at the center of the ischemic zone and at its lateral margin and decreased the peak [K+]e by 0.9 mM at the center (p less than .05) and by 0.1 mM at the margin (p = .10); (2) slowed the development of acidosis and decreased the peak level of acidosis beyond that expected solely as a result of serial occlusions by 0.19 pH units at the center (p less than .05) and by 0.07 pH units at the margin (p = .10); and (3) slowed the development of local activation delay and often prevented the local activation block that was observed during control occlusions. Effects on local activation became less marked at [K+]e levels greater than 9.0 mM, and the effects of verapamil on local activation were not explained solely by its effects on the local rise in [K+]e or fall in pHe. A possible mechanism for this additional effect on local activation is suggested by preliminary results showing a diminution by verapamil of ionic inhomogeneity.

Effect of serial brief ischemic episodes on extracellular K+, pH, and activation in the pig.

This study was performed to determine the reproducibility of the ionic and electrical changes associated with serial ischemic episodes. We used ion-selective and bipolar plunge electrodes to determine the changes in left ventricular extracellular potassium ([K+]e), extracellular pH (pHe), and local activation during sequential 10 min occlusions of the left anterior descending coronary artery separated by 50 min of reperfusion in open-chest anesthetized pigs. We found that uniformly during the initial occlusion, and in approximately 50% of animals during the second occlusion, [K+]e rose more rapidly but to a lower level than in subsequent occlusions. By the third occlusion the changes in [K+]e were reproducible. Extracellular acidosis was greatest in the first occlusion and decreased progressively with each subsequent occlusion. Local activation was characterized by a decrease in spontaneous improvement and increase in block with each successive occlusion. The occurrence of ventricular fibrillation could not be directly attributed to the magnitude of the change in [K+]e or pHe. Moreover, the occurrence of ventricular fibrillation in one occlusion did not necessarily predict its occurrence thereafter. Our results indicate that serial episodes of ischemia are associated with different but predictable changes in ionic and electrical events that may be clinically relevant and that must be appreciated before the results from similar protocols with serial ischemic episodes can be interpreted meaningfully.