| Objective:The objective of this study was to investigate the myocardial and neurological function effects of different therapeutic time windows of mild hypothermia in two types of rabbit ventricular fibrillation model and provides a new experimental evidence for the further researches of the PCAS pathogenesis and prevention. Methods: In our study, we set up different rabbit models of cardiopulmonary resuscitation which are electrical stimulation model(E) and asphyxia model( A). In E group, all of the rabbits were randomly divided into follow groups: normothermic resuscitation group(ENR), mild hypothermia pre-arrest group(EHP), mild hypothermia resuscitation 30 min group(EHRe30), mild hypothermia resuscitation 90 min group(EHRe90). And in A group,all of the rabbits were also randomly divided into follow groups: normothermic resuscitation group(ANR), mild hypothermia pre-arrest group(AHP), mild hypothermia resuscitation 30 min group(AHRe30), mild hypothermia resuscitation 90 min group(AHRe90). We also set control group: normothermic sham group(NS) and hypothermia sham group(HS). The normal temperature was controlled at(39±0.5)℃, and the hypothermia(34.0±1.0)℃. The Blood samples of troponin I(c Tn I), neuron-specific enolase(NSE) and Thioredoxin(Trx), were collected and the index of mean arterial pressure(MAP), left ventricular end-diastolic pressure(LVEDP) and left ventricular pressure raise and fall rate(±dp/dtmax) were observed at before CA 15 min, after ROSC 30 min, 60 min, 120 min, 360 min, 600 min. At 600 th minute after ROSC, heart and brain organization were collected, then light microscopy detection after transferase-mediated deoxyuridine triphosphate-biotin nick end labeling(TUNEL) staining, was used to assess the organizational structure and calculate the apoptosis index. Results: In E group: ○1 Hemodynamics: compared with normal temperature groups, hypothermia groups exhibited lower levels of HR(bpm)(all P < 0.05).Compared with ENR group, EHRe30 group and EHRe90 group, EHP group exhibited higher levels of LVEDP(mm Hg) at 30 min post ROSC(3.4±0.8 vs 4.6±1.0,4.1±0.5,4.3±0.2, all P<0.05). In EHP group, the level of +dp/dtmax(mm Hg/s) was higher than that of ENR group, EHRe30 group and EHRe90 group at 30 min and 120 min post ROSC(30min:10970.2±148.1 vs 11080.9±203.5, 11581.4±203.5. 120min:10391.7±538.2 vs 9688.7±200.3, 8759.8±279.6, all P<0.05). In EHP group, the level of-dp/dtmax(mm Hg/s) was higher than that of ENR group at 30 min, 60 min, 120 min, 360 min and 600 min post ROSC(30min:8557.6±217.8 vs 2113.6±336.9;60min:8186.1±335.5 vs 28871.2±114.2;120min:6221.6±144.6 vs 2335.9±230.2;360min:5368.8±373.5 vs 1923.7±811.2;600min:6153.4±165.3 vs 1880.4±116.6, all P<0.05). ○2 Serology index: Compared with ENR group, EHP group, EHRe30 group and EHRe90 group exhibited lower levels of c Tn I(ng/L) at 30 min,120min and 360 min post ROSC(60min:130.53±11.23 VS 111.86±11.04, 104.27±10.16, 103.49±8.42. 120min:136.09±9.43 vs 122.37±10.69, 105.04±9.03, 105.67±7.60. 360min:138.67±10.17 vs 120.58±9.70, 112.28 ± 12.08, 124.37±8.04, all P<0.05). Compared with EHP group, EHRe30 group and EHRe90 group, ENR group exhibited higher levels of NSE(ug/L) at 60 min,120min and 360 min post ROSC(360min:137.74±2.61 vs 169.59±1.34, 166.43±1.21, 154.35±2.61. 600 min: 163.13 ± 1.33 vs 171.86±1.27, 164.27±1.48, 169.14±2.93, all P<0.05). Compared with ENR group, EHRe30 group and EHRe90 group, ENR group exhibited lower levels of Trx(ng/L) at 60 min,120min, 360 min and 600 min post ROSC(60min:204.21±12.74 vs 171.46±9.86, 186.56±12.18, 174.58 ± 11.55. 120min:210.19±13.22 vs 175.30±9.08, 180.17±11.43, 182.60±12.57. 360min: 192.37 ± 15.01 vs 181.86±10.35, 186.88±12.05, 90.06±11.62. 600min: 199.57±14.13 vs 180.23 ± 10.71, 188.84±11.44, 191.14±12.43, all P<0.05). Compared with EHP group, EHRe30 group and EHRe90 group exhibited higher levels of Trx(ng/L) at 60 min,120min, 360 min and 600 min post ROSC( all P<0.05). There were no significant differences in c Tn I levels among three MTH groups. There were no significant differences in NSE among ENR group, EHRe30 group and EHRe90 group. There were also no signif icant differences in Trx among EHRe30 group and EHRe90 group( all P >0.05).○3 Pathology: Compared with ENR group, less damage to myocardial was found in EHP, EHRe30 and EHRe90 groups. AI(%) was lower in EHP, EHRe30 and EHRe90 groups than that in ENR group [(40.35±9.55)% vs(16.01±6.18)%,(20.10±4.89)%,(24.73±7.10)%, all P<0.05]. Compared with ENR group, less damage to hippocampus CA 1 area was found in EHP, EHRe30 and EHRe90 groups. AI I(%) was lower in EHP, EHRe30 and EHRe90 groups than that in ENR group [62.25±10.43)% vs(20.61±5.02)%,(25.08±3.92)%,(30.33±7.15)%,all P<0.05]. In A group: ○1 Hemodynamics: compared with normal temperature groups, hypothermia groups exhibited lower levels of HR(all P < 0.05). Compared with AHP group, ANR group, AHRe30 group and AHRe90 group exhibited higher levels of MAP(mm Hg) at 30 min post ROSC(80.3±1.1 vs 83.1±2.0, 87.1±1.8, 88.9±2.1, all P<0.05). ○2Serology index: Compared with ANR group, AHP group, AHRe30 group and AHRe90 group exhibited lower levels of c Tn I(ng/L) at 60 min and 120 min post ROSC(60min:131.97±8.36 vs 120.19±9.51, 118.24±9.86, 118.60±9.73. 120min:135.61±9.12 vs 129.26±9.94, 120.57±10.32, 117.28±8.58, all P<0.05). Compared with AHP group, AHRe30 group and AHRe90 group, ANR group exhibited higher levels of NSE(ug/L) at 360 min and 600 min post ROSC(360min:188.34±2.6 vs 263.8±13.4,234.2±11.4,172.4±10.5. 600min:189.16±4.4 vs 273.0±12.1, 229.7±10.5, 165.8±11.9, all P<0.05). Compared with AHP group, ANR group, AHRe30 group and AHRe90 group exhibited higher levels of Trx(ng/L) at 60 min,120min, 360 min and 600 min post ROSC(60min:185.76±5.53 vs 208.67±7.74, 198.73±8.68, 202.88±5.36. 120min:190.11±7.37 vs 219.09±6.05, 196.52±7.95, 216.16±5.40. 360min:188.43±7.24 vs 230.74±8.14, 218.43±8.00, 222.65±6.27. 600min:191.08±6.98 vs 235.75±8.27, 220.17±7.71, 229.05±17.38, all P<0.05). There were no significant differences in NSE and Trx levels among ANR group, AHRe30 group and AHRe90 group. There were no signif icant differences in NSE among ANR group, AHRe30 group and AHRe90 group.( all P>0.05).○3 Pathology: Compared with ANR group, less damage to myocardial was found in AHP, AHRe30 and AHRe90 groups. AI(%) was lower in AHP, AHRe30 and AHRe90 groups than that in ANR group[(51.18±11.16)% vs(17.37±5.30)%,(22.85±3.32)%,(27.99±6.83)%, all P<0.05]. Compared with ANR group, less damage to hippocampus CA 1 area was found in AHP, AHRe30 and AHRe90 groups. AI(%) was lower in AHP, AHRe30 and AHRe90 groups than that in ANR group [(79.13±9.78)% vs(23.07±4.41)%、(27.29±6.24)%,(41.04±5.30)%,all P<0.05]. Between E and A groups: ○1 Hemodynamics: compared with E group, A group exhibited lower levels of MAP at 120 min and 360 min post ROSC( all P<0.05). Compared with E group, A group exhibited lower levels of +dp/dt max at 360 min and 600 min post ROSC( all P<0.05). ○2 Serology index: Compared with E group, A group exhibited higher levels of NSE at 360 min post ROSC(P<0.05). Compared with E group, A group exhibited higher levels of Trx at 60 min,120min, 360 min and 600 min post ROSC( all P<0.05). Compared with the EHRe30 group, AHRe30 group exhibited higher levels of Trx at 360 min post ROSC( P<0.05). Compared with the EHRe90 group in ESAF group, AHRe90 group exhibited higher levels of Trx at 360 min and 600 min post ROSC( all P<0.05). There were no signif icant differences in NSE and Trx among ENR group and ANR group( all P>0.05). ○3Pathology: Compared with the ENR group, more damage to myocardial was found in ANR groups. AI was higher in A groups than that in E group( P<0.05). Compared with the ENR group, more damage to hippocampus CA 1 area was found in ANR groups. AI was higher in A groups than thatin E group(P<0.05). Compared with the EHP group, more damage to hippocampus CA 1 area was found in AHP groups. AI was higher in A groups than that in E group( all P<0.05). Concusions: Our study shows that hypothermia should be initiated as soon as possible( pericardial arrest), and especially early intra-arrest cooling appears to be significantly better than post ROSC cooling and normothermic.The protective effect of MTH is better in E group than in A group. Trx will be as an index of neurological function in PCAS in the future. |
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