Improved myocardial function with supplement of levosimendan to Celsior solution

Area of Science:

• Cardiology
• Cell Biology
• Biochemistry

Background:

• Hypothermic preservation is crucial for organ transplantation but can lead to cardiac dysfunction and apoptosis.
• Levosimendan, a calcium-sensitizing agent, has shown potential in preventing myocardial contractile depression.

Purpose of the Study:

• To investigate the protective effects of levosimendan on cardiac dysfunction and apoptosis in hypothermically preserved rat hearts.
• To elucidate the underlying molecular mechanisms of levosimendan's cardioprotective action.

Main Methods:

• Isolated rat hearts were subjected to hypothermic preservation in Celsior solution with or without levosimendan.
• Cardiac function was assessed by measuring left ventricular developed pressure (LVDP) recovery.
• Apoptosis was evaluated using the apoptosis index, and molecular pathways involving calpain, Bid, and nitric oxide synthase (NOS) were analyzed.

Main Results:

• Hypothermic preservation significantly reduced LVDP recovery and increased apoptosis.
• Levosimendan supplementation enhanced LVDP recovery and reduced apoptosis in a dose-dependent manner.
• Levosimendan inhibited calpain activation and Bid cleavage, increased inducible nitric oxide synthase (iNOS) expression, and its protective effects were mediated by mitochondrial ATP-sensitive potassium (KATP) channels.

Conclusions:

• Levosimendan effectively improves cardiac function recovery and reduces myocyte apoptosis during hypothermic preservation.
• The cardioprotective effects of levosimendan are associated with the inhibition of calpain/Bid pathway and iNOS induction, potentially via mitochondrial KATP channels.