What is the clinical evidence from this study?

Population: Hibernating myocardium (n=23). Intervention: Dobutamine and glibenclamide vs. Sham operation. Primary outcome: Transmural PCr/ATP ratio (p=<0.05).

What question did this study set out to answer?

To determine whether hibernating myocardium maintains normal baseline energetics and whether preserving its energy state during catecholamine stimulation depends on ATP-dependent potassium channel opening.

August 25, 2007AJP Heart and Circulatory Physiology

The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide

Q: What are the key findings of this study?

In chronic hibernating swine myocardium, dobutamine induced an equivalent decrease in PCr/ATP (to 1.73) compared to sham pigs (to 1.69), despite inhibition of ATP-dependent potassium channels.

Q: What question did this study set out to answer?

To determine whether hibernating myocardium maintains normal baseline energetics and whether preserving its energy state during catecholamine stimulation depends on ATP-dependent potassium channel opening.

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Key result

In chronic hibernating swine myocardium, dobutamine induced an equivalent decrease in PCr/ATP (to 1.73) compared to sham pigs (to 1.69), despite inhibition of ATP-dependent potassium channels.

Why the study?

Does glibenclamide and dobutamine alter the myocardial energetic state in a swine model of hibernating myocardium?

Population

23 swine (16 with LAD external constrictor for hibernation model, 7 sham-operated)

Comparison

Glibenclamide and dobutamine (40 microg x kg x… vs Sham-operated swine receiving the same…

Design

Preclinical

Follow-up

10 weeks (for hibernation model development)

Authors

EMEdward O. McFallsHunter Holmes McGuire VA Medical Center RKRosemary F. KellyHeart Failure / Cardiomyopathy QHQingsong HuUniversity of Science and Technology of China

Discussion

Member takes

Implication

No immediate clinical implications; leaves open identification of non-K-ATP adaptive mechanisms preserving energetics in hibernating myocardium.

Key Points

To determine whether hibernating myocardium maintains normal baseline energetics and whether preserving its energy state during catecholamine stimulation depends on ATP-dependent potassium channel opening.
Induced myocardial hibernation in 16 swine via external constriction of the left anterior descending coronary artery (LAD) and evaluated 7 sham-operated swine at 10 weeks.
Measured myocardial bioenergetics via phosphorus-31 magnetic resonance spectroscopy to assess phosphocreatine-to-ATP (PCr/ATP) ratios at baseline, during glibenclamide infusion (0.5 mg/kg bolus with 50 μg/min), and after adding dobutamine (40 μg·kg⁻¹·min⁻¹).
Basal PCr/ATP in the LAD region was equivalent between hibernating (2.15 ± 0.04) and sham hearts (2.11 ± 0.05; P = not significant), despite reduced LAD transmural blood flow in hibernating tissue (0.75 ± 0.11 vs 0.88 ± 0.09 ml·min⁻¹·g⁻¹ remotely; P < 0.01).
During combined glibenclamide and dobutamine infusion, sham hearts exhibited an increased double product (10.4 ± 0.8 to 23.9 ± 4.0 mmHg·beats·min⁻¹·1,000; P < 0.05) and a decrease in PCr/ATP from 2.06 ± 0.06 to 1.69 ± 0.06 (P < 0.05).
Hibernating myocardium experienced an identical decrease in PCr/ATP from 2.04 ± 0.04 to 1.73 ± 0.08 (P < 0.05) under dobutamine, maintaining normal energetic balance despite a 40% lower blood flow response.

Structured PICO

Does glibenclamide and dobutamine alter the myocardial energetic state in a swine model of hibernating myocardium?

Population

23 swine (16 with LAD constrictor-induced hibernation model and 7 sham-operated) assessed at 10 weeks.

Intervention

Glibenclamide (0.5 mg/kg bolus with 50 microg/min iv) and dobutamine (40 microg x kg(-1) x min(-1) iv)

Comparator

Sham-operated swine receiving the same pharmacological challenge

Outcome

Myocardial energetic state in the LAD region assessed by (31)P-NMR spectroscopy (ratio of phosphocreatine to ATP, PCr/ATP)surrogate

Main Result

Absolute Event Rate: 1.73% vs 1.69%

p-value: p=<0.05

In a swine model of hibernating myocardium, the transmural energetic state remains normal during dobutamine stress despite inhibition of ATP-dependent potassium channels, suggesting other adaptive mechanisms protect against ischemia.

Cite This Study

McFalls et al. (2007) studied Hibernating myocardium (n=23). Dobutamine and glibenclamide vs. Sham operation was evaluated on Transmural PCr/ATP ratio (p=<0.05). In chronic hibernating swine myocardium, dobutamine induced an equivalent decrease in PCr/ATP (to 1.73) compared to sham pigs (to 1.69), despite inhibition of ATP-dependent potassium channels.

synapsesocial.com/papers/6aa31139ab549205dac227fe https://doi.org/10.1152/ajpheart.00012.2007

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Implication

No immediate clinical implications; leaves open identification of non-K-ATP adaptive mechanisms preserving energetics in hibernating myocardium.

The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider