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).

METHODS AND 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: L M Owens, T A Fralix, E Murphy, W E Cascio, L S Gettes
• Journal: Circulation (Circulation) Vol. 94 Issue 1 Pg. 10-3 (Jul 01 1996) ISSN: 0009-7322 [Print] United States
• PMID: 8964108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ions
• Phosphocreatine
• Adenosine Triphosphate
• Potassium
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Blood
• Calcium (metabolism)
• Cell Communication
• Electric Conductivity
• Electric Impedance
• Extracellular Space (metabolism)
• Hydrogen-Ion Concentration
• In Vitro Techniques
• Intracellular Membranes (metabolism)
• Ions
• Myocardial Ischemia (metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• Perfusion
• Phosphocreatine (metabolism)
• Potassium (metabolism)
• Rabbits