A new paper from IEMR has given further support to the role of Ca2+/calmodulin-dependent kinase type II (CaMKII) and radical oxygen species (ROS) in reperfusion arrhythmias, but refuted a long-held hypothesis about this common clinical problem.
Reperfusion and return of blood flow to the ischemic area is key in the treatment of myocardial infarction, but can lead to further damage of the heart and arrhythmias. Arrhythmias are particularly common during the early reperfusion phase, and can complicate patient treatment, or in rare cases be fatal.
Early reperfusion arrhythmias result from abnormal calcium handling in cardiomyocytes. Evidence suggests that CaMKII and ROS are important for such perturbations. According to a key hypothesis, the two also interact by ROS-dependent activation of CaMKII.
To investigate this, Marie Synnøve Haugsten Hansen from the Stokke group, used hearts and isolated cells from normal mice, as well as mice with CaMKII resistant to oxidation (MMVV). Hearts and cells from both groups were exposed to protocols of ischemia and reperfusion. The results showed that CaMKII inhibition and ROS-scavenging reduced the incidence of arrhythmic events. However, mice with mutated CaMKII were not protected.
These results provide important insights into the mechanisms underlying reperfusion arrhythmias, and suggests potential strategies for future treatment.