title: Correlation of ischemia-induced extracellular and intracellular ion changes to cell-to-cell electrical uncoupling in isolated blood-perfused rabbit hearts. Experimental Working Group.
abstract: BACKGROUND
  The relationships between the metabolic, ionic, and electrical changes of acute ischemia have not been determined precisely because they have been studied under different experimental conditions. We used ion-selective electrodes, nuclear magnetic resonance spectroscopy, and the four-electrode method to perform four series of experiments in the isolated blood-perfused rabbit heart loaded with 5F-BAPTA during 30 to 35 minutes of no-flow ischemia. We sought to determine the relationship between changes in phosphocreatine (PCr), adenosine triphosphate (ATP), intracellular calcium ([CA2+]i), intracellular pH (pHi) extracellular potassium ([K+]e), extracellular pH (pHe), and whole-tissue resistance (rt).
  
  
  RESULTS
  In the first 8 minutes of ischemia, [K+]e rose from 4.9 to 10.8 mmol/L, PCr fell by 90%, ATP decreased by 25%, and pHi and pHe decreased by 0.5 U, while [Ca2+]i and rt changed only slightly. Between 8 and 23 minutes, [K+]e changed only slightly; pHi, pHe, and ATP continued to fall, and [Ca2+]i rose. rt did not increase until >20 minutes of ischemia, when pHi was <6.0 and [Ca2+]i had increased more than three-fold. The increase in rt, indicating electrical uncoupling, coincided with the third phase of the [K+]e change.
  
  
  CONCLUSIONS
  Our study suggests that cellular uncoupling occurs only after a significant rise in [Ca2+]i and fall in pHi and that these ionic and electrical changes can be identified by the change in [K+]e. Our study underscores the importance of using a common model while attempting to formulate an integrated picture of the ionic, metabolic, and electrical events that occur during acute ischemia.
authors.affiliation: Division of Cardiology, University of North Carolina at Chapel Hill, 27599-7075, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Owens
authors.forename: T A
authors.initials: TA
authors.lastname: Fralix
authors.forename: E
authors.initials: E
authors.lastname: Murphy
authors.forename: W E
authors.initials: WE
authors.lastname: Cascio
authors.forename: L S
authors.initials: LS
authors.lastname: Gettes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001769:Blood; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D004553:Electric Conductivity; D017097:Electric Impedance; D005110:Extracellular Space / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D007477:Ions; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011817:Rabbits
chemical_list: D007477:Ions; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium