Cardioprotection due to preconditioning correlates with increased ecto-5'-nucleotidase activity

Area of Science:

• Cardiovascular Physiology
• Biochemistry
• Cellular Signaling

Background:

• Ischemic preconditioning (IP) is a phenomenon where brief episodes of ischemia protect the heart from subsequent prolonged ischemia.
• The mechanisms underlying the loss of IP's cardioprotective effects over time are not fully understood.
• Ecto-5 '-nucleotidase is an enzyme implicated in cellular protection.

Purpose of the Study:

• To investigate the relationship between the loss of myocardial protection after IP and the deactivation of ecto-5 '-nucleotidase.
• To determine the role of ecto-5 '-nucleotidase activity in mediating the infarct size-limiting effects of IP.

Main Methods:

• Mongrel dogs underwent a protocol of repeated brief coronary occlusions and reperfusions (IP).
• Myocardial infarct size was assessed after a prolonged period of ischemia and reperfusion at various time points after IP.
• Ecto-5 '-nucleotidase activity was measured, and an inhibitor was used to assess its role in IP.

Main Results:

• The infarct size-limiting effect of IP significantly diminished at 30 and 60 minutes after the procedure.
• Ecto-5 '-nucleotidase activity, which was increased by IP, decreased over time, mirroring the loss of protection.
• Infarct size was inversely correlated with ecto-5 '-nucleotidase activity, and inhibition of this enzyme blunted the protective effect of IP.

Conclusions:

• The activity of ecto-5 '-nucleotidase plays a crucial role in the cardioprotection afforded by ischemic preconditioning.
• The gradual deactivation of ecto-5 '-nucleotidase contributes to the time-dependent loss of myocardial protection following IP.