Abstract 139: Protective Effects of Cyclosporine A on the Neuronal Mitochondrial Membrane Potential in Asphyxial Cardiac Arrest Model in Rats
Introduction: Opening mitochondrial permeability transition pore (MPTP) has been implicated as an important mitochondrial event during ischemia reperfusion injury. Cyclosporine A (CsA), as an inhibitor of MPTP, interrupts the cascade reaction of neuron apoptosis, which has been demonstrated to produce neuroprotective effects in traumatic brain injury according to reports.
Hypothesis: We hypothesized CsA reduced the descent of neuronal mitochondrial membrane potential by inhibiting the opening of MPTP in asphyxial cardiac arrest model in rats.
Methods: Twenty-five male Wistar rats (260 - 310 g) were divided into 5 groups (n = 6 each): (1) sham group (S group), rats were anesthetized, surgically prepared and ventilated for 2 h without asphyxial cardiac arrest and CPR; (2) normothermia group (N group), cardiac arrest induced by asphyxia and rectal temperature maintained at 37 ± 0.5°C after return of spontaneous circulation (ROSC); (3) mild hypothermia group (H group), rectal temperature maintained at 33 ± 0.5°C after ROSC; (4) CsA group, CsA (10mg/kg) administered intravenously immediately after ROSC undergoing normothermia; (5) CsA & H group, CsA administered intravenously combined with mild hypothermia. Animals were decapitated after 2 h of resuscitation and the mitochondria of hippocampus in the each group was isolated. The mitochondrial membrane potential was marked by fluorescent probe JC-1 and detected by flow cytometer.
Results: The fluorescence intensity ratio of aggregation and monomer in the H group (0.91 ± 0.05), CsA group (1.0 ± 0.12) and CsA & H group (1.18 ± 0.08) were significantly higher than in the N group (0.68 ± 0.04, p < 0.05 respectively). The fluorescence intensity ratio of aggregation and monomer in the CsA & H group was higher than in the H group and the CsA group (p < 0.05, respectively). All of them were lower than in the S group (1.46 ± 0.03, p < 0.05 respectively).
Conclusions: Either CsA or mild hypothermia used immediately after ROSC improved the neuronal mitochondrial function. Moreover, CsA combined with mild hypothermia treatment enhanced the protective effects. One of the mechanisms of the protective effects of CsA and/or mild hypothermia on neuronal mitochondria was to inhibit mitochondrial membrane depolarisation.
- © 2013 by American Heart Association, Inc.