Title

Adverse Effects on β‐Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long‐Term Cardiac Function

Document Type

Article

Department

Paediatrics and Child Health (East Africa)

Abstract

Background

Ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury. However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor‐mediated signaling of the postischemic heart. The current article examines the effect of IPC or IPoC on the regulation and coupling of β‐adrenergic receptors and their effects on postischemic left ventricular function.

Methods and Results

The β‐adrenergic signal transduction was analyzed in 3‐month‐old Wistar rats for each of the intervention strategies (Sham, ischemia/reperfusion, IPC, IPoC) immediately and 7 days after myocardial infarction. Directly after the infarction a cardioprotective potential was demonstrated for both IPC and IPoC: the infarct size was reduced, apoptosis and production of reactive oxygen species were lowered, and the myocardial tissue was preserved. Seven days after myocardial ischemia, only IPC hearts showed significant functional improvement. Along with a deterioration in fractional shortening, IPoC hearts no longer responded adequately to β‐adrenergic stimulation. The stabilization of β‐adrenergic receptor kinase‐2 via increased phosphorylation of Mdm2 (an E3‐ubiquitin ligase) was responsible for desensitization of β‐adrenergic receptors and identified as a characteristic specific to IPoC hearts.

Conclusions

Immediately after myocardial infarction, rapid and transient activation of β‐adrenergic receptor kinase‐2 may be an appropriate means to protect the injured heart from excessive stress. In the long term, however, induction and stabilization of β‐adrenergic receptor kinase‐2, with the resultant loss of positive inotropic function, leads to the functional picture of heart failure.

Comments

This work was published before the author joined Aga Khan University.

Publication

Journal of the American Heart Association.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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