What does this research mean for the field?

Cardiac subsarcolemmal mitochondria are more susceptible to calcium overload-induced metabolic stress than interfibrillar mitochondria, but exhibit significantly greater responsiveness to the cardioprotective effects of diazoxide. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

September 4, 2012PLoS ONEOpen Access

Cardiac Subsarcolemmal and Interfibrillar Mitochondria Display Distinct Responsiveness to Protection by Diazoxide

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Why the study?

Does diazoxide differentially protect cardiac subsarcolemmal versus interfibrillar mitochondria against Ca2+ overload-mediated inhibition of ATP synthesis?

Population

Isolated subsarcolemmal and interfibrillar mitochondria from the ventricles of male adult Sprague-Dawley rats.

Comparison

Diazoxide (up to 100 μM) vs Vehicle/control and comparison between SSM and…

Design

Preclinical

Authors

EHEkhson HolmuhamedovUniversity of North Carolina at Chapel Hill AOAndrew OberlinMayo Clinic KSKevin R. ShortUniversity of Oklahoma Health Sciences Center

Discussion

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Implication

Animal data suggest subcellular mitochondrial targets for cardioprotection; leaves open translation to human ischemia/reperfusion outcomes.

Structured PICO

Does diazoxide differentially protect cardiac subsarcolemmal versus interfibrillar mitochondria against Ca2+ overload-mediated inhibition of ATP synthesis?

Population

Isolated subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria from the ventricles of male adult Sprague-Dawley rats (n=6 mitochondrial isolations).

Intervention

Diazoxide (up to 100 μM)

Comparator

Vehicle/control (absence of diazoxide) and comparison between SSM and IFM subpopulations

Outcome

Responsiveness to diazoxide against Ca2+ overload-mediated inhibition of ATP synthesis and oxidative phosphorylationsurrogate

Diazoxide preferentially protects subsarcolemmal mitochondria over interfibrillar mitochondria against calcium overload-induced energetic failure, suggesting a specific subcellular target for cardioprotection during ischemia/reperfusion.

Cite This Study

Holmuhamedov et al. (2012) studied this question.

synapsesocial.com/papers/6a1b8a0990759efe6f0c8496 https://doi.org/10.1371/journal.pone.0044667

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Implication

Animal data suggest subcellular mitochondrial targets for cardioprotection; leaves open translation to human ischemia/reperfusion outcomes.

Cardiac Subsarcolemmal and Interfibrillar Mitochondria Display Distinct Responsiveness to Protection by Diazoxide

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Cardiac Subsarcolemmal and Interfibrillar Mitochondria Display Distinct Responsiveness to Protection by Diazoxide

Discussion

Member takes

Implication

Structured PICO

Cite This Study

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