Effect of pre-arrest and post-arrest mild hypothermia on myocardial function of ventricular fibrillation after restoration of spontaneous circulation in rabbits / 中华危重病急救医学

ABSTRACT

ObjectiveTo study the effect of pre-arrest and post-arrest mild hypothermia after restoration of spontaneous circulation (ROSC) on myocardial function, ultrastructure, apoptosis of myocardial cells in rabbits with ventricular fibrillation.Methods Sixty-two male New Zealand rabbits were randomly allocated into five groups namely normothermic control group (NTC group,n = 10), hypothermia control group (HTC group,n = 10), normothermic resuscitation group (NTR group,n = 14), hypothermia pre-arrest group (HPRA group,n = 14), and hypothermia post-arrest group (HPOA group,n = 14). The normal temperature was controlled at (39.0±0.5)℃, and the hypothermia (33.5±0.5)℃. Ventricular fibrillation cardiac arrest (CA) was reproduced in rabbits by transcutaneous epicardium electrical stimulation. The parameters of hemodynamics were monitored dynamically for 4 hours in all the groups, including heart rate (HR), left ventricular end diastolic and systolic pressure (LVEDP/LVESP), maximal rate of increase/decrease in left ventricular pressure (±dp/dt max), and mean arterial pressure (MAP). The body temperature of rabbits in hypothermia groups was maintained by surface cooling for 4 hours followed by rewarming. The survived rabbits were sacrificed at 48 hours after resuscitation, and myocardial apical tissue was harvested for observation of ultrastructure with electronic microscope, and to observe apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.Results① Resuscitation investigation there was no significant difference in rate of ROSC, time of CPR and energy of defibrillation among HPRA, HPOA, and NTR groups [rate of ROSC 85.71%, 71.43%, 71.43%; time of CPR (seconds) 45.3±30.2, 61.2±41.3, 82.3±63.8;energy of defibrillation (J) 14.3±8.9, 22.0±15.5, 25.0±15.8, allP> 0.05].② Hemodynamics compared with normal temperature groups, animals in hypothermia groups exhibited lower levels of HR (allP< 0.05). Compared with NTR group, HPRA group exhibited higher levels of LVESP (mmHg, 1 mmHg = 0.133 kPa) at 0.5, 1, 2 and 3 hours post ROSC (0.5 hour 103.8±14.3 vs. 91.6±13.3, 1 hour 107.2±14.1 vs. 82.7±8.5, 2 hours 109.0±16.9 vs. 88.8±12.9, 3 hours 109.1±14.6 vs. 89.3±14.3, allP< 0.05). Compared with NTR group and HPOA group, HPRA group exhibited lower levels of LVEDP (mmHg) at 0.5 hour post ROSC (3.70±0.85 vs. 7.61±2.73, 7.02±3.12, both P< 0.05). Compared with NTR group, HPRA group exhibited lower levels of LVEDP at 1 hour post ROSC (4.34±1.44 vs. 6.99±1.96,P< 0.05). In HPRA group, the level of+dp/dt max (mmHg/s) was higher than that of NTR group and HPOA group at 1 hour and 2 hours post ROSC (1 hour 2 759.5±321.6 vs. 2 123.0±304.5, 2 283.7±234.2, 2 hours2 730.6±425.1 vs. 2 221.5±392.9, 2 252.6±476.0, allP< 0.05). There were no significant differences in -dp/dt max and MAP levels among three CPR groups.③ The survival rate at 48 hours post ROSC of NTR, HPRA and HPOA groups was 60%, 75%, and 100%, respectively. Compared with NTR group, higher survival rate was found in HPOA group at 48 hour post ROSC (P< 0.05).④ Compared with NTR group, less damage to myocardial ultrastructure was found in HPRA and HPOA groups. Apoptosis index (AI) was lower in HPRA and HPOA groups than that in NTR group [(28.05±9.82) %, (26.39±8.98) % vs. (42.02±13.36) %, bothP< 0.05].Conclusions Our study shows that mild hypothermia has no effect on ROSC rate. Pre-arrest hypothermia can ameliorate myocardial systolic function of rabbit in early stage after ROSC, and it has no negative influence on diastolic function. Post-arrest mild hypothermia produces no negative influence on myocardial function of rabbit, but it improves 48 hours survival rate in ROSC rabbits. Both pre-arrest and post-arrest mild hypothermia therapy can attenuate myocardial injury in CA model of rabbits by ameliorating mitochondrial injuries and suppressing apoptosis of myocardial cells.