PASSIVE ELECTRICAL-PROPERTIES, MECHANICAL-ACTIVITY, AND EXTRACELLULAR POTASSIUM IN ARTERIALLY PERFUSED AND ISCHEMIC RABBIT VENTRICULAR MUSCLE - EFFECTS OF CALCIUM ENTRY BLOCKADE OR HYPOCALCEMIA

The relation among passive electrical resistive properties, longitudinal conduction velocity, extracellular potassium concentration, [K+](o), and mechanical activity was investigated in the isolated rabbit papillary muscle during normal arterial perfusion and no-flow ischemia in the presence and absence of verapamil, or a reduced extracellular Ca2+ concentration [Ca2+](o). During normal arterial perfusion, verapamil (0.5 μM, free [Ca2+](o) = 1.0 mM) and hypocalcemic blood perfusate (free [Ca2+](o) = 0.4 mM) reduced the maximal isometric twitch tension by 48% and 78%, depolarized the resting membrane by +3 and +7 mV, decreased the extracellular longitudinal resistance (r(o)) by 15% and 26%, and increased conduction velocity by 4% and 6%, respectively. The changes in conduction velocity during these interventions were consistent with those predicted by linear cable theory (+3% and +9%) for the observed changes in r(o). In contrast, verapamil shortened whereas a reduced [Ca2+](o) lengthened action potential duration. Comparison of simultaneously measured longitudinal whole tissue resistance (r(t)), intracellular longitudinal resistance (r(i)), [K+](o), and resting tension during ischemia showed a close association between abrupt cell-to-cell electrical uncoupling, development of ischemic contracture, and the secondary rise of [K+](o), which all started to develop after approximately 15 minutes of ischemia. Electrical cell-to-cell uncoupling was completed within 15 minutes. In the presence of verapamil, the relation among the onset of electrical cell-to-cell uncoupling, secondary rise of [K+](o), and onset of ischemic contracture in ischemia was qualitatively the same as in its absence; however, these events were postponed by approximately 10 minutes, and the rates of contracture development and uncoupling were diminished. Conduction velocity decreased after 12 minutes of ischemia from 54 of 36 cm/sec in the absence of and from 61 to 45 cm/sec in the presence of verapamil. This slowing effect on impulse conduction could not be attributed to changes of electrical cell-to-cell coupling because at this time an increase in r(i) had not yet taken place. In the presence of a reduced [Ca2+](o), the resting tension and r(i) increased almost immediately after the onset of ischemia. Although the resting tension rose progressively throughout the course of ischemia, the r(i) showed a biphasic increase characterized by an early transient increase that reached a peak at 8 minutes (+87%) and a second, irreversible increase beginning at approximately 12 minutes. This final onset of electrical cell-to-cell uncoupling and the secondary rise of [K+](o) were not different from the findings with a normal [Ca2+](o). The decrease of conduction velocity was greater with reduced than with normal [Ca2+](o), and ischemic conduction block occurred earlier.