What question did this study set out to answer?

Determine the therapeutic effects of chronic, selective pharmacological activation of PPARδ on cardiac function, metabolism, and remodeling in a postmyocardial infarction model of congestive heart failure.

July 1, 2007Journal of Cardiovascular Pharmacology

PPARδ Activation Normalizes Cardiac Substrate Metabolism and Reduces Right Ventricular Hypertrophy in Congestive Heart Failure

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Why the study?

Does the PPARdelta-specific agonist GW610742X improve cardiac function and metabolism in Sprague-Dawley rats post-myocardial infarction?

Population

Sprague-Dawley rats post-myocardial infarction (MI)

Comparison

PPARdelta-specific agonist GW610742X at 30 and… vs Sham animals and untreated MI rats

Design

Preclinical

Follow-up

6-9 weeks

Authors

BJBeat M. JuckerCardiac Imaging CDChristopher DoeRaNA Therapeutics (United States)CSChristine G. SchnackenbergGlaxoSmithKline (United States)

Discussion

Member takes

Implication

Hypothesizes PPARδ agonism as metabolic target in experimental post-MI HF; leaves open human translation and any LV functional role.

Key Points

Determine the therapeutic effects of chronic, selective pharmacological activation of PPARδ on cardiac function, metabolism, and remodeling in a postmyocardial infarction model of congestive heart failure.
Sprague-Dawley rats received the PPARδ-specific agonist GW610742X (30 and 100 mg/kg/day) for 6 to 9 weeks immediately following myocardial infarction.
In vivo cardiac performance and energetics were evaluated using magnetic resonance imaging and spectroscopy.
Relative carbohydrate versus fat oxidation was measured using a 1-(13)C glucose clamp, alongside hemodynamic assessments and RT-PCR gene expression analysis.
Myocardial infarction reduced LV ejection fraction by 43% and the phosphocreatine/ATP ratio by 14%, but GW610742X treatment did not significantly alter either parameter or infarct size.
GW610742X normalized the post-infarction decrease in relative fat oxidation rate (which had dropped 58% in the LV and 54% in the RV) in a dose-dependent manner and upregulated lipid metabolism genes such as CD36, CPT1, and UCP3.
Treatment produced a 22% to 48% reduction in right ventricular hypertrophy and pulmonary congestion (P < 0.01), accompanied by a greater than 7-fold reduction in RV atrial natriuretic peptide expression (P < 0.05).

Structured PICO

Does the PPARdelta-specific agonist GW610742X improve cardiac function and metabolism in Sprague-Dawley rats post-myocardial infarction?

Population

Sprague-Dawley rats post-myocardial infarction (MI)

Intervention

PPARdelta-specific agonist GW610742X at 30 and 100 mg/kg/day for 6-9 weeks initiated immediately post-MI

Comparator

Sham animals and untreated MI rats

Outcome

Cardiac function, energetics, and relative cardiac carbohydrate versus fat oxidationsurrogate

Pharmacological activation of PPARdelta normalizes cardiac substrate metabolism and reduces right ventricular hypertrophy and pulmonary congestion in a rat model of post-MI heart failure.

Cite This Study

Jucker et al. (2007) studied this question.

synapsesocial.com/papers/6a70d91b84cc45bb7bdfd71b https://doi.org/10.1097/fjc.0b013e31804b4163

Topics

HFrEF treatment Heart failure HFpEF management

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PPARδ Activation Normalizes Cardiac Substrate Metabolism and Reduces Right Ventricular Hypertrophy in Congestive Heart Failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

PPARδ Activation Normalizes Cardiac Substrate Metabolism and Reduces Right Ventricular Hypertrophy in Congestive Heart Failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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