July 1, 1999AJP Heart and Circulatory Physiology
Transmural metabolic heterogeneity at high cardiac work states
Key result
In dogs with coronary stenosis, pacing decreased subendocardial CrP/ATP to 1.65 (P<0.05), paralleling hypoperfusion, whereas dobutamine caused transmural changes not matching hypoperfusion.
Population
Normal dogs with a hydraulic occluder producing a left anterior descending coronary artery stenosis (n=24)
Comparison
Tachycardia induced by rapid pacing or… vs Comparison between pacing-induced and…
Design
Preclinical
Authors
Discussion
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Implication
Highlights stressor-specific metabolic ischemia in stenosis; hypothesis-generating for human translation.
Key Points
- To compare transmural high-energy phosphate depletion during oxidative stress induced by pacing versus dobutamine infusion in myocardium with a flow-limiting coronary stenosis.
- Conducted in normal dogs with left anterior descending coronary artery stenosis induced via a hydraulic occluder.
- Tachycardia was triggered by rapid electrical pacing (200 beats/min, n=11) or dobutamine infusion (20 µg/kg/min iv, n=13) to achieve matched heart rates.
- Measured myocardial blood flow using radioactive microspheres and transmural creatine phosphate (CrP), ATP, and inorganic phosphate via localized 31P NMR spectroscopy.
- Both pacing and dobutamine induced similar reductions in subendocardial-to-subepicardial flow ratios (0.66 ± 0.06 vs. 0.63 ± 0.08, respectively).
- Stenosis plus pacing significantly decreased the CrP/ATP ratio exclusively in the subendocardium (from 2.00 ± 0.07 to 1.65 ± 0.08, P < 0.05) with no significant alteration in the subepicardium.
- Stenosis plus dobutamine led to widespread transmural energy depletion, most prominent in the subepicardium (CrP/ATP decreased from 2.33 ± 0.11 to 1.67 ± 0.12) alongside subendocardial depletion (CrP/ATP decreased from 1.99 ± 0.09 to 1.64 ± 0.12).
Structured PICO
P
Population
Normal dogs with a hydraulic occluder producing a left anterior descending coronary artery stenosis (n=24)
I
Intervention
Tachycardia induced by rapid pacing (200 beats/min, n=11) or dobutamine infusion (20 micrograms/kg/min iv, n=13)
C
Comparator
Comparison between pacing-induced and dobutamine-induced tachycardia
O
Outcome
Transmural distribution of high-energy phosphate (HEP) depletion (CrP, ATP, Pi) and myocardial blood flow (MBF)surrogate
Main Result
p-value: p=<0.05
In a canine model of coronary stenosis, pacing-induced tachycardia causes subendocardial metabolic ischemia matching hypoperfusion, whereas dobutamine-induced inotropic stimulation causes transmural metabolic changes that do not correspond to the hypoperfusion pattern.
Cite This Study
Gong et al. (1999) studied Coronary stenosis with tachycardia (n=24). Dobutamine infusion vs. Rapid pacing (200 beats/min) was evaluated on Transmural distribution of high-energy phosphate depletion (CrP/ATP ratio) (p=<0.05). In dogs with coronary stenosis, pacing decreased subendocardial CrP/ATP to 1.65 (P<0.05), paralleling hypoperfusion, whereas dobutamine caused transmural changes not matching hypoperfusion.