September 3, 1999Circulation Research
Intravenous Allopurinol Decreases Myocardial Oxygen Consumption and Increases Mechanical Efficiency in Dogs With Pacing-Induced Heart Failure
Key result
Intravenous allopurinol decreased myocardial oxygen consumption by 49% (P=0.002) and increased mechanical efficiency by 122% (P=0.04) in dogs with pacing-induced heart failure.
Why the study?
Does intravenous allopurinol improve inotropic properties and mechanical efficiency without increasing myocardial oxygen consumption in dogs with pacing-induced heart failure?
Population
15 conscious dogs, including 10 control dogs and 5 dogs with pacing-induced heart failure
Comparison
Allopurinol 200 mg IV vs Baseline measurements prior to allopurinol…
Design
Preclinical
Authors
Discussion
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Implication
Should not change clinical HF management; extends experimental evidence on allopurinol's energetics to warrant human translation studies.
Key Points
- To determine whether allopurinol exerts a positive inotropic effect without increasing myocardial energy expenditure in conscious dogs with pacing-induced heart failure.
- Conscious healthy control dogs (n=10) and dogs with pacing-induced heart failure (n=5) received allopurinol (200 mg IV).
- Left ventricular contractility ((dP/dt)max, preload-recruitable stroke work, ventricular elastance), myocardial oxygen consumption, and cardiac xanthine oxidase activity were evaluated.
- In heart failure dogs, allopurinol increased (dP/dt)max by +24.4±8.7% (P=0.03), preload-recruitable stroke work by +28.1±5.3% (from 55.8±9.1 to 84.9±12.2 mm Hg, P=0.02), and ventricular elastance from 6.0±1.6 to 10.5±2.2 mm Hg/mm (P=0.03).
- Allopurinol reduced myocardial oxygen consumption by -49±4.6% (P=0.002) and increased mechanical efficiency by +122±42% (P=0.04) in failing hearts, where xanthine oxidase activity was fourfold higher than in controls (387±125 vs. 78±72 pmol/min·mg⁻¹, P=0.04).
Structured PICO
Does intravenous allopurinol improve inotropic properties and mechanical efficiency without increasing myocardial oxygen consumption in dogs with pacing-induced heart failure?
P
Population
15 conscious dogs, including 10 control dogs and 5 dogs with pacing-induced heart failure
I
Intervention
Allopurinol 200 mg IV
C
Comparator
Baseline measurements prior to allopurinol administration, and comparison between heart failure and control dogs
O
Outcome
Changes in inotropic properties ((dP/dt)max, preload-recruitable stroke work, ventricular elastance), myocardial oxygen consumption, and mechanical efficiencysurrogate
Main Result
Effect estimate: -49%
p-value: p=0.002
Allopurinol acts as a unique inotrope in a canine model of heart failure, increasing contractility while simultaneously reducing myocardial oxygen consumption and boosting mechanical efficiency.
Cite This Study
Ekelund et al. (1999) studied Pacing-induced heart failure (n=15). Allopurinol vs. Control dogs (without heart failure) was evaluated on Myocardial oxygen consumption in heart failure dogs (-49%, p=0.002). Intravenous allopurinol decreased myocardial oxygen consumption by 49% (P=0.002) and increased mechanical efficiency by 122% (P=0.04) in dogs with pacing-induced heart failure.