Wei Zhang1, Jonathan Tam2, Koichiro Shinozaki3, Tai Yin3, Joshua W Lampe4, Lance B Becker4, Junhwan Kim5. 1. Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA. 2. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA. 3. Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Emergency Medicine, Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA. 4. Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Emergency Medicine, Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA. 5. Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Emergency Medicine, Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA. Electronic address: jkim46@northwell.edu.
Abstract
BACKGROUND: Cardiac arrest is one of the leading causes of death with a very high mortality rate. No therapeutic drug that can be administered during resuscitation has been reported. Mitochondrial dysfunction is believed to play an important role for the pathogenesis of cardiac arrest. SS-31, a tetra-peptide, has been shown to protect mitochondria from ischaemia/reperfusion injury. Therefore, we tested whether SS-31 improves rat survival after prolonged cardiac arrest. METHODS: Rats were randomised into two groups. After 25minutes of asphyxia-induced cardiac arrest, rats were resuscitated with or without SS-31 using cardiopulmonary bypass resuscitation. Rat survival was followed for additional 4.5hours using haemodynamic monitoring. The blood gas was analysed for surviving rats at multiple time points. RESULTS AND CONCLUSIONS: After 5hours, 5 of 10 rats survived in the SS-31 group whereas only 1 of 10 rats survived in the control group (p=0.026). At 90minutes after resuscitation, the blood lactate level in the SS-31 treated rats (4.29±2.5mmol/L) was significantly lower than in control rats (7.36±3.1mmol/L, p=0.026), suggesting mitochondrial aerobic respiration was improved with SS-31 treatment. Overall, our data show the potential of SS-31 as a novel therapeutic in cardiac arrest.
BACKGROUND:Cardiac arrest is one of the leading causes of death with a very high mortality rate. No therapeutic drug that can be administered during resuscitation has been reported. Mitochondrial dysfunction is believed to play an important role for the pathogenesis of cardiac arrest. SS-31, a tetra-peptide, has been shown to protect mitochondria from ischaemia/reperfusion injury. Therefore, we tested whether SS-31 improves rat survival after prolonged cardiac arrest. METHODS:Rats were randomised into two groups. After 25minutes of asphyxia-induced cardiac arrest, rats were resuscitated with or without SS-31 using cardiopulmonary bypass resuscitation. Rat survival was followed for additional 4.5hours using haemodynamic monitoring. The blood gas was analysed for surviving rats at multiple time points. RESULTS AND CONCLUSIONS: After 5hours, 5 of 10 rats survived in the SS-31 group whereas only 1 of 10 rats survived in the control group (p=0.026). At 90minutes after resuscitation, the blood lactate level in the SS-31 treated rats (4.29±2.5mmol/L) was significantly lower than in control rats (7.36±3.1mmol/L, p=0.026), suggesting mitochondrial aerobic respiration was improved with SS-31 treatment. Overall, our data show the potential of SS-31 as a novel therapeutic in cardiac arrest.
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