Improved 4- and 6-hour myocardial preservation by hypoxic preconditioning

Area of Science:

• Cardiology
• Cellular Biology
• Biochemistry

Background:

• Hypoxic preconditioning can protect the myocardium from ischemic-reperfusion injury.
• The underlying cellular mechanisms, including ionic shifts and protein expression, require further investigation for prolonged hypothermic storage.

Purpose of the Study:

• To investigate the role of intracellular ionic alterations, heat-shock proteins (hsps), and catalase in hypoxic preconditioning's protective effects on postischemic heart function.
• To examine these mechanisms in a model of prolonged hypothermic cardiac storage.

Main Methods:

• Isolated working rat hearts were divided into control and hypoxically preconditioned groups.
• Hearts underwent hypothermic storage (4-6 hours) after cardioplegic arrest.
• Myocardial function, intracellular ion concentrations ([Na+]i, [K+]i, [Mg2+]i, [Ca2+]i), and mRNA levels of hsp 70 and catalase were measured.

Main Results:

• Hypoxically preconditioned hearts showed improved function (aortic flow, dP/dtmax) and altered ion balance ([K+]i increased, [Na+]i and [Ca2+]i decreased) after storage compared to controls.
• Steady-state mRNA levels of catalase and hsp 70 were significantly upregulated in the preconditioned hearts.
• The upregulation of catalase and hsp 70 peaked at 4 hours of storage.

Conclusions:

• Intracellular ionic alterations contribute to the protective effects of hypoxic preconditioning.
• Upregulation of catalase and heat-shock protein 70 gene expression is a key mechanism involved.
• These factors collectively enhance postischemic cardiac function during prolonged hypothermic storage.