The effects of resolvin D1 on myocardial dysfunction after cardiopulmonary resuscitation in swine and its potential mechanisms / 中华急诊医学杂志

ABSTRACT

Objective To establish a porcine model of cardiopulmonary resuscitation to explore the effectiveness of resolvin D1 in improving post-resuscitation myocardial dysfunction and its potential mechanisms.Methods Twenty-eight male domestic pigs weighing 36 ± 3 kg were utilized.The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation.The animals were randomly divided into 4 groups (n =7 each)sham operation group (group S),cardiopulmonary resuscitation group (group CPR),low-dose resolvin D1 group (group LRD),and high-dose resolvin D1 group (group HRD).The animals in group S only got the general preparation without the procedure of cardiac arrest and resuscitation.At 5 min after resuscitation,the doses of resolvin D1 0.3 μg/kg and 0.6 μg/kg were respectively injected via the femoral vein of pigs in LRD and HRD groups,and meanwhile the equal volume of vehicle was given into the animals in the other two groups.At 3 h,6 h and 24 h after resuscitation,the changes of stroke volume (SV) and global ejection fraction (GEF) were evaluated by a PiCCO monitor,and meanwhile the concentration of cardiac troponin I (cTNI) in serum was measured.At 24 h after resuscitation,the pigs were sacrificed,and myocardial tissue was obtained for the determination of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6),malondialdehyde (MDA),and superoxide dismutase (SOD) activity.Results Compared with group S,significantly decreased SV and GEF and markedly increased concentration of serum cTNI were observed in the other three groups with post-resuscitation myocardial dysfunction (all P ＜ 0.05).Compared with group CPR,the values of SV and GEF were significantly increased while the concentration of serum cTNI was significantly decreased in LRD and HRD groups [SV (ml)28 ±5,31 ±5 vs.23 ±4 at 3 hrs,32 ±3,36 ±6 vs.27 ± 6 at6 hrs,35 ±5,41 ±5 vs.29±5 at24 hrs;GEF (％)17±2,19±2 vs.14±1 at3 hrs,20±2,23 ± ±3 vs.16 ±3 at 6 hrs,23 ±2,26 ±3 vs.20 ±2 at 24 hrs;cTNI (pg/ml)247 ±34,230 ±26 vs.324 ± 56 at 3 hrs,553 ± 37,501 ± 34 vs.611 ± 44 at 6 hrs,436 ± 23,371 ± 29 vs.553 ± 47 at 24 hrs,all P ＜ 0.05].Compared with group LRD,myocardial function and serum markers were further significantly improved in group HRD (all P ＜ 0.05).The inflammation and oxidative stress in myocardial tissue were observed in all the animals experiencing cardiac arrest and resuscitation,which were indicated by increased levels of TNF-α,IL-6 and MDA and decreased SOD activity.Compared with group CPR,the levels of TNF-α,IL-6 and MDA were significantly decreased while SOD activity was significantly increased in LRD and HRD groups [TNF-α (pg/ml)442 ±87,218 ±55 vs.653 ± 112;IL-6 (pg/ml)563 ± 68,403±61vs.824±117;MDA (nmol/mg)3.95±0.96,2.54±1.21vs.6.37±1.26;SOD (U/mg)2.27±0.93,3.36±0.74vs.0.89±0.31,all P＜0.05].The morbidity of myocardial inflammation and oxidative stress were further significantly ameliorated in group HRD evidenced by the figure of biomarkers compared with group LRD (all P ＜ 0.05).Conclusions Resolvin D1 can improve post-resuscitation myocardial dysfunction in a dose-dependent manner in swine,and the mechanism is related to the inhibition of inflammation and oxidative stress.