What does this research mean for the field?

Protein kinase C (PKC) activation decreases myocardial oxygen consumption and increases contractile efficiency in the heart by modulating both the contractile machinery and excitation-contraction coupling. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine the effects of protein kinase C activation on myocardial oxygen consumption and cardiac mechanoenergetics.

November 1, 2001AJP Heart and Circulatory Physiology

Activation of PKC decreases myocardial O2consumption and increases contractile efficiency in rats

Q: What is the clinical evidence from this study?

Study design: Other. Population: cardiac mechanoenergetics. Intervention: Phorbol 12-myristate 13-acetate (PMA) with or without chelerythrine vs. Baseline/Control. Primary outcome: Contractile efficiency and PVA-independent VO2 (p=<0.05).

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Key result

PKC activation with PMA in isolated rat hearts decreased PVA-independent VO2 by 28% and increased contractile efficiency by 41% (P<0.05), effects that were abolished by chelerythrine.

Why the study?

Does PKC activation with PMA alter myocardial O2 consumption and contractile efficiency in isolated rat hearts?

Population

Isolated rat hearts

Comparison

PKC activator phorbol 12-myristate 13-acetate… vs Baseline or hearts without PMA/chelerythrine

Design

Preclinical

Authors

TNTeruo NoguchiCardiac Imaging ZCZengyi ChenUniversity of Vermont SBStephen P. BellHoward Hughes Medical Institute

Discussion

Member takes

Implication

No clinical implications from this rat model; extends mechanistic evidence on PKC and myocardial efficiency.

Key Points

To determine the effects of protein kinase C activation on myocardial oxygen consumption and cardiac mechanoenergetics.
Perfused isolated rat hearts with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) in the presence or absence of the inhibitor chelerythrine.
Assessed contractile efficiency and nonmechanical energy expenditure by measuring linear myocardial oxygen consumption (VO2) relative to the pressure-volume area (PVA).
PMA decreased myocardial contractility (Emax by -30 ± 8%; P < 0.05) and increased coronary perfusion pressure (+58 ± 11%; P < 0.01) without altering left ventricular end-diastolic pressure.
PMA reduced PVA-independent VO2 by 28 ± 8% (P < 0.05) and increased contractile efficiency by 41 ± 8% (P < 0.05), while basal metabolism remained unchanged.
Pretreatment with chelerythrine completely prevented PMA-induced vasoconstriction, negative inotropy, and alterations in oxygen consumption and contractile efficiency.

Structured PICO

Does PKC activation with PMA alter myocardial O2 consumption and contractile efficiency in isolated rat hearts?

Population

Isolated rat hearts

Intervention

PKC activator phorbol 12-myristate 13-acetate (PMA) with or without pretreatment with the PKC inhibitor chelerythrine

Comparator

Baseline or hearts without PMA/chelerythrine

Outcome

Contractile efficiency (assessed as the reciprocal of the slope of the linear myocardial O2 consumption pressure-volume area relation) and myocardial O2 consumption (VO2)surrogate

Main Result

p-value: p=<0.05

PKC activation by PMA decreases myocardial oxygen consumption and increases contractile efficiency in isolated rat hearts, effects that are reversed by PKC inhibition.

Cite This Study

Noguchi et al. (2001) studied cardiac mechanoenergetics. Phorbol 12-myristate 13-acetate (PMA) with or without chelerythrine vs. Baseline/Control was evaluated on Contractile efficiency and PVA-independent VO2 (p=<0.05). PKC activation with PMA in isolated rat hearts decreased PVA-independent VO2 by 28% and increased contractile efficiency by 41% (P<0.05), effects that were abolished by chelerythrine.

synapsesocial.com/papers/6a1c2f1b1567d2fc4d5fb9ff https://doi.org/10.1152/ajpheart.2001.281.5.h2191

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Activation of PKC decreases myocardial O2consumption and increases contractile efficiency in rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Activation of PKC decreases myocardial O2consumption and increases contractile efficiency in rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider