Myocardial ischemic contracture. Metabolites affect rigor tension development and stiffness

Area of Science:

• Biochemistry
• Cardiovascular Physiology
• Cellular Mechanics

Background:

• Myocardial ischemia reduces phosphocreatine (PCr) and Mg(2+)-ATP, increasing inorganic phosphate (Pi), protons, and Mg(2+)-ADP.
• These metabolic changes may influence rigor tension development in cardiac muscle fibers.

Purpose of the Study:

• To investigate the role of key metabolites (PCr, Pi, Mg(2+)-ADP, protons) in rigor tension development in rat ventricular fibers.
• To understand the mechanisms underlying ischemic contracture and increased myocardial stiffness.

Main Methods:

• Utilized Triton X-100-skinned rat ventricular fibers.
• Induced rigor tension by varying Mg(2+)-ATP concentrations in the presence or absence of PCr.
• Controlled ionic environment ([Ca2+], [free Mg2+], ionic strength) and pH to mimic physiological conditions.

Main Results:

• PCr depletion significantly increased the Mg(2+)-ATP required for half-maximal rigor tension.
• Pi and acidic pH modulated rigor tension, with acidic pH decreasing maximal tension and tension-to-stiffness ratio.
• Mg(2+)-ADP increased maximal rigor tension, suggesting a role in ischemic contracture.

Conclusions:

• Decreased PCr and elevated Mg(2+)-ADP accumulation contribute to ischemic contracture and myocardial stiffness.
• Myofibrillar creatine kinase activity is vital for preventing rigor tension and maintaining cardiac function during ischemia.