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NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts
Published on: July 24, 2012
Increased hypoxic stress decreases AMP hydrolysis in rabbit heart
L A Gustafson1, C J Zuurbier, J E Bassett
1Center for Bioengineering, University of Washington, Seattle 98195, USA. lorig@physiol.med.vu.nl
Cardiovascular Research
|February 26, 2000
Summary
During repeated ischemia, AMP hydrolysis is inhibited, conserving nucleotides. This nucleotide conservation may occur through an inosine monophosphate (IMP) accumulation pathway, especially under 10% flow conditions.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Metabolic Regulation
Background:
- Cytosolic 5'nucleotidase (5NT) and AMP deaminase regulate AMP conversion, impacting ATP resynthesis during reoxygenation.
- AMP hydrolysis is crucial for preserving cellular energy during ischemia.
- 5NT activity is known to decrease during severe underperfusion (5% flow).
Purpose of the Study:
- To investigate the regulation of AMP hydrolysis during less severe underperfusion (10% flow).
- To determine if hypoxia reactivates 5NT activity during a second ischemic period.
- To elucidate nucleotide conservation mechanisms during repeated ischemia.
Main Methods:
- Langendorff-perfused rabbit hearts subjected to two 30-min underperfusion periods (10% flow).
- 31P NMR spectroscopy and coronary venous effluent analysis.
- Mathematical modeling of myocardial energetics and metabolism kinetics.
Main Results:
- A single 30-min underperfusion (10% flow) downregulates AMP hydrolysis.
- Lower 5NT activity explains data during a second underperfusion, even with added hypoxia.
- A discrepancy in purine effluent suggests IMP accumulation via AMP deaminase contributes to nucleotide conservation.
Conclusions:
- AMP hydrolysis to adenosine is prominent in early ischemia, preserving energy.
- Nucleotides are conserved during a second ischemic period due to stable inhibition of AMP hydrolysis.
- Under 10% flow, nucleotide conservation may involve an IMP-accumulatory pathway.
