Mechanical factors affecting protein turnover in isolated rat hearts

Area of Science:

• Cardiovascular Physiology
• Cardiac Metabolism
• Protein Synthesis Regulation

Background:

• Cardiac work and substrate availability influence myocardial protein synthesis.
• Understanding the interplay between mechanical load and metabolic substrates is crucial for cardiac health.

Purpose of the Study:

• To investigate the effects of cardiac work and varying substrate conditions on protein synthesis and degradation in the heart.
• To determine the role of mechanical parameters, specifically aortic pressure and ventricular stretch, in regulating cardiac protein synthesis.

Main Methods:

• Isolated heart perfusion models (Langendorff and working heart preparations).
• Varied substrate perfusions (glucose, plasma-like mixtures, insulin, lactate, pyruvate).
• Manipulation of aortic pressure and ventricular filling/drainage to alter mechanical load.
• Measurement of protein synthesis, degradation, nitrogen balance, and oxygen consumption.

Main Results:

• Cardiac work increased protein synthesis with glucose or normal plasma-like mixtures, but not with high insulin concentrations.
• Increased aortic pressure accelerated protein synthesis, even when pressure development was prevented or hearts were arrested, suggesting mechanical stretch is a primary driver.
• Nitrogen balance improved in working hearts compared to Langendorff preparations, and was positive with optimal substrate mixtures.

Conclusions:

• Mechanical stretch, induced by increased aortic pressure, is a significant factor promoting cardiac protein synthesis.
• The effects of cardiac work on protein synthesis are modulated by substrate availability and hormonal milieu.
• Optimized substrate supply and reduced mechanical load can lead to positive nitrogen balance in the perfused heart.