Effects of limb ischemic post-conditioning alone or its combination with therapeutic hypothermia on systemic inflammatory response and lung injury after cardiopulmonary resuscitation / 中华危重病急救医学

ABSTRACT

Objective To investigate the effects of limb ischemic post-conditioning (LIpostC) alone or its combination with therapeutic hypothermia (TH) on systemic inflammatory response and lung injury after cardiac arrest (CA) and resuscitation. Methods Twenty-one healthy male pigs weighing (37±2) kg were randomly divided into 3 groups (n = 7 each) control group, LIpostC group, and LIpostC+TH group. The animal model was established by 10 minutes of untreated CA and then 5 minutes of cardiopulmonary resuscitation (CPR).Coincident with the start of CPR, LIpostC was induced by four cycles of 5 minutes of limb ischemia followed by 5 minutes of reperfusion in the LIpostC and LIpostC+TH groups. After successful resuscitation, TH was implemented by surface cooling to reach a temperature of 32-34℃ until 4 hours post-resuscitation, followed by a re-warming rate of 1 ℃/h for 4 hours in the LIpostC+TH group. Normal temperature was maintained in the control and LIpostC groups. The resuscitation outcomes in each group were recorded during CPR. At 15 minutes prior to CA (baseline) and during 4 hours post-resuscitation, the level of arterial lactate was measured and PaO2/FiO2 was calculated, and extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were measured meanwhile by a PiCCO monitor. At 15 minutes prior to CA (baseline) and during 24 hours post-resuscitation, the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA). Results Six animals in each group were successfully resuscitated. Coronary perfusion pressure (CPP), duration of resuscitation, number of shocks and epinephrine dosage during CPR were not statistically significant among the three groups. The baseline of arterial lactate, PaO2/FiO2, EVLWI, PVPI and cytokines prior to CA were also not statistically significant among the three groups. The levels of serum TNF-α and IL-6 after resuscitation were gradually increased in all the three groups; however, the values of TNF-αand IL-6 were significantly lower in the LIpostC and LIpostC+TH groups than that in the control group, and they were further decreased in the LIpostC+TH group when compared to the LIpostC group [TNF-α (ng/L) 305±22 vs. 343±26 at 4 hours, 350±29 vs. 389±18 at 24 hours; IL-6 (ng/L) 239±14 vs. 263±19 at 24 hours, all P < 0.05]. The levels of lactate reached the peak at 2 hours post-resuscitation and then gradually decreased in all the three groups; it finally returned to the baseline in the LIpostC and LIpostC+TH groups, which was markedly lower than that in the control group (mmol/L 1.4±0.7, 1.2±0.3 vs. 3.1±1.7, both P < 0.05). During 4 hours post-resuscitation, PaO2/FiO2 was significantly higher and EVLWI and PVPI were markedly lower in the LIpostC and LIpostC+TH groups than that in the control group; additionally, PaO2/FiO2 and EVLWI were further improved in the LIpostC+TH group than the LIpostC group [4-hour PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa) 391±26 vs. 361±20; 4-hour EVLWI (mL/kg) 10.1±1.5 vs. 12.1±1.2, both P < 0.05]. Conclusion LIpostC can be used to alleviate systemic inflammatory response and lung injury after porcine CA and CPR, and its combination with TH further enhanced its protective effects.