What is the clinical evidence from this study?

Population: Cardiac contractility. Intervention: PMCA4b overexpression vs. Wild-type littermates. Primary outcome: Change in end-systolic elastance (Ees) after isoproterenol injection (p=<0.05).

January 23, 2007CirculationOpen Access

Neuronal Nitric Oxide Synthase Signaling in the Heart Is Regulated by the Sarcolemmal Calcium Pump 4b

Q: What are the key findings of this study?

Overexpression of PMCA4b in transgenic mice significantly attenuated the beta-adrenergic inotropic response compared to wild-type mice (Ees change 11% vs 40%, p<0.05) via modulation of nNOS activity.

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Key result

Overexpression of PMCA4b in transgenic mice significantly attenuated the beta-adrenergic inotropic response compared to wild-type mice (Ees change 11% vs 40%, p<0.05) via modulation of nNOS activity.

Population

Transgenic mice overexpressing either human PMCA4b or PMCA ct120 in the heart, and wild-type littermates…

Comparison

Transgenic overexpression of PMCA4b or PMCA… vs Wild-type littermates; saline treatment.

Design

Preclinical

Authors

DODelvac OceandyManchester Academic Health Science Centre ECElizabeth J. CartwrightHeart Failure / Cardiomyopathy MEMichael EmersonUniversity of North Carolina at Chapel Hill

Discussion

Member takes

Implication

Hypothesis-generating in mice; does not support clinical use of PMCA4b modulation and leaves therapeutic translation open.

Structured PICO

Population

Transgenic mice overexpressing human PMCA4b or PMCA ct120 in the heart, aged 3 to 5 months, used to study the regulation of neuronal nitric oxide synthase and cardiac contractility.

Intervention

Transgenic overexpression of PMCA4b or PMCA ct120; treatment with isoproterenol and/or specific nNOS inhibitor (N omega-propyl-L-arginine).

Comparator

Wild-type littermates; saline treatment.

Outcome

Beta-adrenergic contractile response (measured by end-systolic elastance [Ees] and dP/dtmax-EDV after isoproterenol injection).surrogate

Main Result

Absolute Event Rate: 11% vs 40%

p-value: p=<0.05

The sarcolemmal calcium pump PMCA4b regulates cardiac contractility in vivo by modulating neuronal nitric oxide synthase (nNOS) activity, demonstrating a novel signaling function independent of its calcium extrusion role.

Limitations

Animal model findings may not directly translate to human physiology
Absolute levels of PMCA4 and nNOS protein could not be compared directly due to different antibody affinities

Cite This Study

Oceandy et al. (2007) studied Cardiac contractility. PMCA4b overexpression vs. Wild-type littermates was evaluated on Change in end-systolic elastance (Ees) after isoproterenol injection (p=<0.05). Overexpression of PMCA4b in transgenic mice significantly attenuated the beta-adrenergic inotropic response compared to wild-type mice (Ees change 11% vs 40%, p<0.05) via modulation of nNOS activity.

synapsesocial.com/papers/6a6f4c71e5469ee92be04e26 https://doi.org/10.1161/circulationaha.106.643791

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Neuronal Nitric Oxide Synthase Signaling in the Heart Is Regulated by the Sarcolemmal Calcium Pump 4b

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Neuronal Nitric Oxide Synthase Signaling in the Heart Is Regulated by the Sarcolemmal Calcium Pump 4b

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider