What is the clinical evidence from this study?

Population: Ischemia-reperfusion injury. Intervention: MDL28170 or doxycycline vs. Untreated ischemia-reperfusion. Primary outcome: Degradation of Na+-K+ ATPase subunits and activity of Na+-K+ ATPase, calpain, and MMP-2.

What question did this study set out to answer?

To evaluate the role of proteases in sarcolemmal Na+-K+ ATPase subunit degradation and enzymatic activity during ischemia-reperfusion injury in isolated rat hearts.

April 1, 2013The FASEB Journal

Activation of proteases and changes in Na+‐K+ ATPase subunits in hearts subjected to ischemia‐reperfusion

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Key result

MDL28170 preserves Na+-K+ ATPase activity better than doxycycline during rat ischemia-reperfusion injury.

Why the study?

Does inhibition of calpain or MMP-2 prevent degradation of Na+-K+ ATPase subunits and activity in rat hearts subjected to ischemia-reperfusion injury?

Key Points

To evaluate the role of proteases in sarcolemmal Na+-K+ ATPase subunit degradation and enzymatic activity during ischemia-reperfusion injury in isolated rat hearts.
Induced global ischemia in rat hearts for 15, 30, and 60 minutes, followed by reperfusion intervals of 5, 10, 20, and 40 minutes.
Measured protein degradation of Na+-K+ ATPase subunits (α-1, α-2, β-1, β-2) alongside activity assays for Na+-K+ ATPase, calpain, and MMP-2.
Perfused hearts with the calpain inhibitor MDL28170 or the MMP inhibitor doxycycline to assess protective effects against injury.
Global ischemia and subsequent reperfusion significantly elevated calpain and MMP-2 activities while depleting β-1 and β-2 subunits and depressing Na+-K+ ATPase enzymatic activity.
Reperfusion intensified both the activation of calpain and MMP-2 and the reduction of Na+-K+ ATPase subunit protein levels.
MDL28170 attenuated ischemia-reperfusion-induced cardiac contracture and preserved Na+-K+ ATPase activity more effectively than doxycycline.

Structured PICO

Does inhibition of calpain or MMP-2 prevent degradation of Na+-K+ ATPase subunits and activity in rat hearts subjected to ischemia-reperfusion injury?

Population

Rat hearts subjected to global ischemia and reperfusion to evaluate the role of proteases in sarcolemmal Na+-K+ ATPase subunits.

Intervention

Perfusion with MDL28170 (calpain inhibitor) or doxycycline (MMP-2 inhibitor)

Comparator

Untreated rat hearts subjected to ischemia-reperfusion

Outcome

Extent of degradation of Na+-K+ ATPase subunits (α-1, α-2, β-1, and β-2) and activity of Na+-K+ ATPase, calpain, and MMP-2surrogate

Inhibition of calpain with MDL28170 is more effective than MMP-2 inhibition with doxycycline in preventing Na+-K+ ATPase degradation during myocardial ischemia-reperfusion injury in a rat model.

Discussion

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Implication

Protease-mediated Na-K ATPase degradation may occur in rat I/R; leaves open clinical relevance and therapeutic targeting.

Cite This Study

Müller et al. (2013) studied Ischemia-reperfusion injury. MDL28170 or doxycycline vs. Untreated ischemia-reperfusion was evaluated on Degradation of Na+-K+ ATPase subunits and activity of Na+-K+ ATPase, calpain, and MMP-2. In rat hearts subjected to ischemia-reperfusion injury, activation of calpain and MMP-2 depressed Na+-K+ ATPase activity and degraded its subunits, with MDL28170 being more effective than doxycycline.

synapsesocial.com/papers/6aa17a44556578a1cb444019 https://doi.org/10.1096/fasebj.27.1_supplement.1129.8

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Activation of proteases and changes in Na+‐K+ ATPase subunits in hearts subjected to ischemia‐reperfusion

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Activation of proteases and changes in Na+‐K+ ATPase subunits in hearts subjected to ischemia‐reperfusion

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider