What is the clinical evidence from this study?

Population: Normal cardiac function (rat model). Intervention: cpTOME vs. Control. Primary outcome: Ca(2+) spark frequency (p=0.05).

What question did this study set out to answer?

This study investigates how Epac activation affects calcium sensitivity in rat cardiac muscle during low inotropic states.

October 15, 2015Clinical and Experimental Pharmacology and Physiology

Depotentiation of intact rat cardiac muscle unmasks an Epac‐dependent increase in myofilament Ca²⁺ sensitivity

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Key result

Epac activation with cpTOME increased Ca2+ spark frequency in isolated rat myocytes from 7 to 32/100 μm3/s (P=0.05) and increased myofilament Ca2+ sensitivity in depotentiated trabeculae.

Key Points

This study investigates how Epac activation affects calcium sensitivity in rat cardiac muscle during low inotropic states.
Used 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate to activate Epac in isolated myocytes.
Measured Ca(2+) spark frequency and amplitude with fura-2 ratio in isolated myocytes and multicellular trabeculae.
Determined the effects of Epac activation on myofilament Ca(2+) sensitivity by manipulating extracellular calcium levels.
Activation of Epac increased Ca(2+) spark frequency from about 7 to 32/100 μm(3)/s (P = 0.05).
No significant changes were observed in calcium transient amplitude (P = 0.35) or peak stress (P = 0.20).
In depotentiated trabeculae, Epac activation raised myofilament Ca(2+) sensitivity, which was inhibited by KN-93.

Structured PICO

Population

Rat heart ventricular preparations (isolated myocytes, n=10; multicellular trabeculae, n=7)

Intervention

8-(4-chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate (cpTOME), an analogue of cAMP that activates Epac

Comparator

Control

Outcome

Excitation-contraction coupling parameters including Ca2+ spark frequency, amplitude of Ca2+ transients, peak stress, and myofilament Ca2+ sensitivitysurrogate

Main Result

Absolute Event Rate: 32% vs 7%

p-value: p=0.05

Epac activation increases myofilament Ca2+ sensitivity in depotentiated rat cardiac muscle, suggesting it may be a potential therapeutic target to increase contraction strength during low inotropic states.

Discussion

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Implication

Epac activation may enhance contractility in low-inotropy states; hypothesis-generating in rat models, human relevance unknown.

Cite This Study

Kaur et al. (2015) studied Normal cardiac function (rat model). cpTOME vs. Control was evaluated on Ca(2+) spark frequency (p=0.05). Epac activation with cpTOME increased Ca2+ spark frequency in isolated rat myocytes from 7 to 32/100 μm3/s (P=0.05) and increased myofilament Ca2+ sensitivity in depotentiated trabeculae.

synapsesocial.com/papers/6a20b793515be2b4c6f9ee25 https://doi.org/10.1111/1440-1681.12504

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Depotentiation of intact rat cardiac muscle unmasks an Epac‐dependent increase in myofilament Ca²⁺ sensitivity

Key Points

Structured PICO

Main Result

Discussion

Implication

Cite This Study

Depotentiation of intact rat cardiac muscle unmasks an Epac‐dependent increase in myofilament Ca²⁺ sensitivity

Key Points

Structured PICO

Main Result

Discussion

Implication

Cite This Study

Also Consider

Also Consider