Affiliation:
1. the Division of Cardiology, University of North Carolina at Chapel Hill, and the Laboratory of Molecular Biophysics (E.M.), National Institute of Environmental Health Sciences, Research Triangle Park, NC.
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 ([Ca
2+
]
i
), intracellular pH (pH
i
), extracellular potassium ([K
+
]
e
), extracellular pH (pH
e
), and whole-tissue resistance (r
t
).
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 pH
i
and pH
e
decreased by 0.5 U, while [Ca
2+
]
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 [Ca
2+
]
i
rose. r
t
did not increase until >20 minutes of ischemia, when pH
i
was <6.0 and [Ca
2+
]
i
had increased more than threefold. The increase in r
t
, 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 [Ca
2+
]
i
and fall in pH
i
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Reference29 articles.
1. Gettes LS Cascio WE. Effect of acute ischemia on cardiac electrophysiology. In: Fozzard HA ed. The Heart and Cardiovascular System: Scientific Foundations. 2nd ed. New York NY: Raven Press Ltd; 1992.
2. Synthesis and characterization of 19F NMR chelators for measurement of cytosolic free Ca
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