CORRELATION OF ISCHEMIA-INDUCED EXTRACELLULAR AND INTRACELLULAR ION CHANGES TO CELL-TO-CELL ELECTRICAL UNCOUPLING IN ISOLATED BLOOD-PERFUSED RABBIT HEARTS

Background The relationships between the metabolic, ionic, and electri cal changes of acute ischemia have not been determined precisely becau se they have been studied under different experimental conditions. We used ion-selective electrodes, nu clear magnetic resonance spectroscop y, and the four-electrode method to perform four series of experiments in the isolated blood-perfused rabbit heart loaded with 5F-BAPTA duri ng 30 to 35 minutes of no-flow ischemia. We sought to determine the re lationship between changes in phosphocreatine (PCr), adenosine triphos phate (ATP), intracellular calcium ([Ca2+](i)), intracellular pH (pH(i )), extracellular potassium ([K+](e)), extracellular pH (pH(c)), and w hole-tissue resistance (r(t)). Methods and Results In the first 8 minu tes of ischemia, [K+](e) rose from 4.9 to 10.8 mmol/L, PCr fell by 90% , ATP decreased by 25%, and pH(i) and pH(e), decreased by 0.5 U, while [Ca2+](i) and r(t) changed only slightly. Between 8 and 23 minutes, [ K+](e) changed only slightly; pH(i), pH(e). and ATP continued to fall, and [Ca2+](i) rose. r(t) did not increase until > 20 minutes of ische mia, when pH(i) was < 6.0 and [Ca2+](i) had increased more than threef old. The increase in r(t), indicating electrical uncoupling, coincided with the third phase of the [K+](e) change. Conclusions Our study sug gests that cellular uncoupling oc curs only after a significant rise i n [Ca2+](i) and fall in pH(i) and that these ionic and electrical chan ges can be identified by the change in [K+](e). Our study underscores the importance of using a common model while attempting to formulate a n integrated picture of the ionic, metabolic, and electrical events th at occur during acute ischemia.