April 1, 2001Journal of Cardiovascular Pharmacology
Levosimendan Increases Diastolic Coronary Flow in Isolated Guinea-Pig Heart by Opening ATP-Sensitive Potassium Channels
Why the study?
Does levosimendan increase diastolic coronary flow velocity through the opening of K(ATP) channels in isolated guinea-pig hearts?
Population
Isolated Langendorff perfused spontaneously beating guinea-pig hearts
Comparison
Levosimendan (0.01-1 microM) vs Absence and presence of glibenclamide; pinacidil…
Design
Preclinical
Authors
Discussion
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Implication
Supports K(ATP)-mediated coronary vasodilation by levosimendan in isolated hearts; leaves open translation to human coronary disease.
Key Points
- This research aims to determine if levosimendan increases coronary flow by activating K(ATP) channels in coronary smooth muscle.
- Measured diastolic coronary flow velocity in a Langendorff perfused guinea-pig heart.
- Evaluated effects of levosimendan with and without glibenclamide and pinacidil.
- Used protein kinase C inhibitor bisindolylmaleimide to assess interactions.
- Levosimendan increased diastolic coronary flow velocity concentration-dependently (0.01-1 microM).
- Glibenclamide noncompetitively antagonized the effects of levosimendan (0.1 microM).
- Additive effects of bisindolylmaleimide and levosimendan on diastolic coronary flow suggest synergistic action.
Structured PICO
Does levosimendan increase diastolic coronary flow velocity through the opening of K(ATP) channels in isolated guinea-pig hearts?
P
Population
Isolated Langendorff perfused spontaneously beating guinea-pig hearts
I
Intervention
Levosimendan (0.01-1 microM)
C
Comparator
Absence and presence of glibenclamide (0.1 microM); pinacidil used as reference compound
O
Outcome
Diastolic coronary flow velocity (DCFV)surrogate
Levosimendan induces coronary vasodilation in isolated guinea-pig hearts by opening K(ATP) channels, likely binding to the unphosphorylated form of the channel at a different site than pinacidil.
Cite This Study
Kaheinen et al. (2001) studied this question.