Editors' ChoiceCRITICAL CARE MEDICINE

Breaking up is bad for the heart

See allHide authors and affiliations

Science Translational Medicine  28 Jan 2015:
Vol. 7, Issue 272, pp. 272ec19
DOI: 10.1126/scitranslmed.aaa5556

Every minute counts in the case of sudden cardiac arrest when the entire body lacks blood flow and oxygen. The brain is most vulnerable, and if the heart cannot be restarted promptly, serious neurological damage can occur within minutes. To date, there are no drugs that when given during treatment of cardiac arrest can improve resuscitation and protect vital heart and brain function. Now, Sharp et al. describe a new mitochondria-targeted therapy that has promise to change how cardiac arrest is treated.

Mitochondria, the powerhouses of cells, tend to produce free radicals instead of energy when oxygen is lacking. These damaging free radicals can cause cellular injury in vital organs. Mitochondria increase their free radical production by splitting apart in response to lack of oxygen. This split tends to occur when mitochondria encounter dynamin-related protein 1 (Drp1). Realizing this mechanism, Sharp et al. applied a small-molecule inhibitor of Drp1, called Mdivi-1, to inhibit mitochrondrial splitting during cardiopulmonary resuscitation after cardiac arrest in a mouse model. They found that Mdivi-1 prevented Drp1dephosphorylation, inhibited its transport to the mitochondria, and reduced mitochondrial splitting. Mdivi-1 also decreased the total time needed to restart the heart and improved heart function after resuscitation when measured using echocardiography. Most importantly, Drp1 inhibition improved survival and decreased neurological injury when assessed 3 days later as using a behavioral neurological scoring system developed for mice. This approach requires further verification in animal models prior to translation to humans. However, keeping mitochondria from breaking up during cardiac arrest may be a viable and important preventer of organ damage.

W. W. Sharp et al., Inhibition of the mitochondrial fission protein dynamin-related protein 1 improves survival in a murine cardiac arrest model. Crit. Care Med. 43, e38–47 (2015). [Abstract]

Navigate This Article