What is the clinical evidence from this study?

Population: Evolving cardiac dysfunction (n=48). Intervention: Atenolol vs. Angiotensin II + 48-hour tachycardia pacing alone. Primary outcome: Chamber stiffness (end-diastolic pressure) and metalloproteinase (MMP) abundance and activity (p=<0.001).

What question did this study set out to answer?

To determine whether sustained metalloproteinase activation and diastolic chamber stiffening induced by angiotensin II during evolving cardiac dysfunction are mediated by sympathostimulation.

April 14, 2000Circulation ResearchOpen Access

β-Blockade Prevents Sustained Metalloproteinase Activation and Diastolic Stiffening Induced by Angiotensin II Combined With Evolving Cardiac Dysfunction

Q: What are the key findings of this study?

High-dose atenolol prevented marked chamber stiffening (end-diastolic pressure >25 mm Hg, P<0.001) and increased metalloproteinase activity induced by Angiotensin II and tachycardia pacing in dogs.

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

To determine whether sustained metalloproteinase activation and diastolic chamber stiffening induced by angiotensin II during evolving cardiac dysfunction are mediated by sympathostimulation.

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Key result

High-dose atenolol prevented marked chamber stiffening (end-diastolic pressure >25 mm Hg, P<0.001) and increased metalloproteinase activity induced by Angiotensin II and tachycardia pacing in dogs.

Why the study?

Does atenolol prevent sustained metalloproteinase activation and diastolic stiffening induced by Angiotensin II combined with evolving cardiac dysfunction in dogs?

Population

48 dogs instrumented to serially assess conscious ventricular mechanics, MMP abundance and activity, and…

Comparison

Cotreatment with high-dose atenolol or low-dose… vs Angiotensin II + 48hP alone, Angiotensin II…

Design

Preclinical

Follow-up

5 days

Authors

HSHideaki SenzakiNihon Institute of Medical Science NPNazareno PaolocciHeart Failure & Transplant YGYehezkiel A. GluzbandNational Institutes of Health

Discussion

Member takes

Implication

Does not support atenolol use in patients with evolving HF; leaves open beta-blockade effects on MMP activity and diastolic function in humans.

Key Points

To determine whether sustained metalloproteinase activation and diastolic chamber stiffening induced by angiotensin II during evolving cardiac dysfunction are mediated by sympathostimulation.
Instrumented 48 dogs to serially evaluate conscious ventricular mechanics, metalloproteinase abundance and activity, and myocardial histopathology.
Administered 48-hour tachycardia pacing alone, 5-day intravenous angiotensin II infusion alone (15 ± 5 ng·kg⁻¹·min⁻¹), or pacing combined with angiotensin II, alongside high-dose or partial beta-blockade with atenolol.
Tachycardia pacing combined with angiotensin II more than doubled chamber stiffness (end-diastolic pressure >25 mm Hg, P<0.001) and elevated 92-kDa gelatinase abundance and activity, while neither insult alone altered stiffness.
High-dose atenolol cotreatment completely prevented both chamber stiffening and metalloproteinase activation, whereas partial beta-blockade failed to prevent either abnormality.
Myocellular damage accompanied by neutrophil and fibroblast infiltration occurred with angiotensin II and pacing, which was suppressed by high-dose atenolol without altering total collagen content.

Structured PICO

Does atenolol prevent sustained metalloproteinase activation and diastolic stiffening induced by Angiotensin II combined with evolving cardiac dysfunction in dogs?

Population

48 dogs instrumented to serially assess conscious ventricular mechanics, MMP abundance and activity, and myocardial histopathology, subjected to 48-hour tachycardia pacing (48hP) combined with 5 days of Angiotensin II (15+/-5 ng. kg(-1). min(-1) IV)

Intervention

Cotreatment with high-dose atenolol or low-dose (partial) atenolol

Comparator

Angiotensin II + 48hP alone, Angiotensin II alone, or 48hP alone

Outcome

Chamber stiffness (end-diastolic pressure), MMP abundance and activity (principally 92-kDa gelatinase), and myocardial histopathologysurrogate

Main Result

p-value: p=<0.001

High-dose beta-blockade prevents Angiotensin II-mediated sympathostimulation from inducing myocardial MMP activation and diastolic stiffening in a canine model of evolving heart failure.

Cite This Study

Senzaki et al. (2000) studied Evolving cardiac dysfunction (n=48). Atenolol vs. Angiotensin II + 48-hour tachycardia pacing alone was evaluated on Chamber stiffness (end-diastolic pressure) and metalloproteinase (MMP) abundance and activity (p=<0.001). High-dose atenolol prevented marked chamber stiffening (end-diastolic pressure >25 mm Hg, P<0.001) and increased metalloproteinase activity induced by Angiotensin II and tachycardia pacing in dogs.

synapsesocial.com/papers/6a0b995f71bf22a7f695d5d2 https://doi.org/10.1161/01.res.86.7.807

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Implication

Does not support atenolol use in patients with evolving HF; leaves open beta-blockade effects on MMP activity and diastolic function in humans.

β-Blockade Prevents Sustained Metalloproteinase Activation and Diastolic Stiffening Induced by Angiotensin II Combined With Evolving Cardiac Dysfunction

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

β-Blockade Prevents Sustained Metalloproteinase Activation and Diastolic Stiffening Induced by Angiotensin II Combined With Evolving Cardiac Dysfunction

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

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