Reassessment of mitochondrial cyclophilin D as a target for improving cardiac arrest outcomes in the era of therapeutic hypothermia

International audience; Uncertainty exists regarding whether cyclophilin D (CypD), a mitochondrial matrix protein that plays a key role in ischemia-reperfusion injury, can be a pharmacological target for improving outcomes after cardiac arrest (CA), especially when therapeutic hypothermia is used. Using CypD knockout mice (CypD−/−), we investigated the effects of loss of CypD on short-term and medium-term outcomes after CA. CypD−/− mice or their wild-type (WT) littermates underwent either 5-minute CA followed by resuscitation with/without hypothermia at 33-34 C (targeted temperature reached within minutes after resuscitation), or a sham procedure. Brain and cardiac injury were assessed using echocardiography, neurological scores, MRI and biomarkers. Seven-day survival was compared using Kaplan-Meier estimates. The rate of restoration of spontaneous circulation was significantly higher in CypD−/− mice (with shorter cardiac massage duration) than in WT mice (p