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  • Title: Post-cardiac arrest myocardial dysfunction is improved with cyclosporine treatment at onset of resuscitation but not in the reperfusion phase.
    Author: Huang CH, Tsai MS, Hsu CY, Su YJ, Wang TD, Chang WT, Chen WJ.
    Journal: Resuscitation; 2011 Dec; 82 Suppl 2():S41-7. PubMed ID: 22208177.
    Abstract:
    AIM OF STUDY: Significant myocardial dysfunction and high mortality occur after whole-body ischaemia-eperfusion injuries in the post-cardiac arrest status. The inhibition of mitochondrial permeability transition pore (mPTP) opening during ischaemia-reperfusion can ameliorate injuries in the specific organs. We investigated the effect and therapeutic window of pharmacological inhibition of mPTP opening in cardiac arrest. METHODS: Forty male Wistar rats were resuscitated after cardiac arrest induced by 8.5 min of asphyxia. Cyclosporine (10 mg/kg) was administered intravenously at onset of resuscitation in protocol 1 study and administered 3 min after ROSC in protocol 2 with placebo control in both. RESULTS: Left ventricular systolic (dP/dt 40), diastolic (maximal negative dP/dt) functions and cardiac output were improved in the group with cyclosporine treatment at onset of resuscitation compared to control group (p < 0.01, respectively). Seventy-two hour survival was better in the group with cyclosporine treatment at onset of resuscitation compared to control (p = 0.046). Left ventricular systolic and diastolic function, cardiac output and 72 h survival were not improved in the group with cyclosporine treatment 3 min after ROSC. The severity of mitochondrial damage under electronic microscopy, mPTP opening, mitochondrial respiratory control ratio and ADP:O ratio were ameliorated in the group with cyclosporine treatment at onset of resuscitation (p< 0.05, respectively) but not in the group with cyclosporine treatment at 3 min after ROSC. CONCLUSIONS: Post-cardiac arrest myocardial dysfunction and survival can be improved by cyclosporine treatment at onset of resuscitation, but not by the cyclosporine treatment at 3 min after ROSC.
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