What does this research mean for the field?

Despite similar total wall stress, cardiac afterload induces maladaptive fibrotic hypertrophy and CaMKII-dependent apoptosis with higher mortality, whereas preload induces Akt activation with better preserved function and lower mortality. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research examines how different hemodynamic loads affect cardiac remodeling and function in mice.

August 24, 2010CirculationOpen Access

Differential Cardiac Remodeling in Preload Versus Afterload

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Why the study?

Does afterload (TAC) versus preload (shunt) result in different cardiac remodeling phenotypes in mice?

Population

Mice (including wild-type and calcium/calmodulin-dependent protein kinase IIdelta-knockout mice)

Comparison

Transverse aortic constriction to induce afterload vs Aortocaval shunt to induce preload, and sham…

Design

Preclinical

Follow-up

Up to 8 weeks

Authors

KTKarl ToischerHeart Failure & Transplant ARAdam G. RokitaUniversity of Göttingen BUBernhard UnsöldInterventional / Structural Cardiology

Discussion

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Implication

Should not alter clinical practice; leaves open translation of load-specific remodeling to human HF.

Key Points

This research examines how different hemodynamic loads affect cardiac remodeling and function in mice.
Used mice with transverse aortic constriction (TAC) and aortocaval shunt to model afterload and preload, respectively.
Measured wall stress, left ventricular weight, calcium signaling, and gene expression at specified time points post-surgery.
Compared TAC and shunt mice to sham controls over time for functional and structural outcomes.
TAC showed 40% increase in systolic wall stress and shunt showed a 277% increase in diastolic wall stress (P<0.05).
Calcium/calmodulin-dependent protein kinase II signaling increased in TAC, while Akt phosphorylation increased in shunt mice.
After 8 weeks, TAC mice exhibited lower fractional shortening and higher mortality compared to shunt mice.

Structured PICO

Does afterload (TAC) versus preload (shunt) result in different cardiac remodeling phenotypes in mice?

Population

Mice (including wild-type and calcium/calmodulin-dependent protein kinase IIdelta-knockout mice)

Intervention

Transverse aortic constriction (TAC) to induce afterload

Comparator

Aortocaval shunt to induce preload, and sham surgery

Outcome

Cardiac remodeling phenotypes including wall stress, hypertrophy, calcium cycling, apoptosis, fibrosis, fractional shortening, and mortalitysurrogate

Afterload and preload induce distinct cardiac remodeling phenotypes in mice, with afterload causing maladaptive fibrotic hypertrophy and preload leading to better preserved function.

Cite This Study

Toischer et al. (2010) studied this question.

synapsesocial.com/papers/6a1e98eb6b4935698da413c3 https://doi.org/10.1161/circulationaha.110.943431

Topics

Heart failure HFrEF treatment

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Differential Cardiac Remodeling in Preload Versus Afterload

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Differential Cardiac Remodeling in Preload Versus Afterload

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Topics

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