Abstract 18031: Impact of Diabetes and Acute Hyperglycemia on Myocardial Ischemia/reperfusion Injury and Ischemic Preconditioning: Evidence From Real-Time Two-Photon Imaging
Background: Diabetes worsens clinical outcome of ischemic heart disease, but inconsistency exists about the susceptibility to myocardial ischemia/reperfusion (MI/R) injury and the protective effect of ischemic preconditioning (IPC) in diabetic hearts. Furthermore, hyperglycemia has been reported to be associated with poor prognosis after MI/R, but it remains uncertain whether hyperglycemia is a cause of poor outcome or result from severity of illness itself. Loss of mitochondrial membrane potential (ΔΨm) and subsequent mitochondrial collapse is a key step in the cell death process during myocardial MI/R. Using the real-time two-photon imaging that we established recently, we monitored ΔΨm in the perfused diabetic or hyperglycemic hearts subjected to MI/R.
Methods and results: Hearts from Goto-Kakizaki (GK) type 2 diabetic rats and control rats were Langendorff-perfused, loaded with an indicator of ΔΨm, tetramethylrhodamine ethyl-ester, and were subjected to Is/R (30 min ischemia, 40 min reperfusion) or IPC/Is/R: IPC (3 cycles of 5 min ischemia, 5 min reperfusion) before Is/R. Ischemia was global no-flow ischemia, and reperfusion was achieved by the restart of perfusion. The two-photon imaging revealed that diabetic GK hearts underwent earlier ΔΨm loss during Is/R, compared with control hearts, but the extent of mitochondrial damage was comparable at the end of the protocol. Hyperglycemic control hearts (33.3 mmol/L) exerted earlier and more robust ΔΨm loss than normoglycemic GK hearts (11.1 mmol/L). Finally, IPC remarkably reduced the loss of ΔΨm induced by Is/R in control heats, but it failed to protect against Is/R in both diabetic GK and hyperglycemic hearts. Normalizing blood sugar level prior to Is/R partially attenuated the severity of ΔΨm loss.
Conclusions: Both diabetes and hyperglycemia made the hearts more susceptible to MI/R injury, and canceled the protective effect of IPC. Hyperglycemic state during MI/R exerted even poorer outcomes; early and intensive correction of blood sugar level may reduce myocardial damage.
- © 2010 by American Heart Association, Inc.