Protective effect of ulinastatin on myocardial injury after cardiopulmonary resuscitation in pigs

Abstract

Objective To evaluate the protective effect of ulinastatin (UTI) on myocardial injury after post-cardiac arrest syndrome (PCAS) of cardiopulmonary resuscitation in pigs. Methods Twelve male 3-4 months pigs were randomly divided into two groups, UTI group and control group. The ventricular fibrillation (VF) animal model was replicated by programmed stimulation method. Among the 12 pigs, 11 pigs were successfully resuscitated by CPR after 5 min VF, of which, 6 pigs were in the UTI group and 5 pigs in the control group. Immediately after resuscitation, pigs in the UTI group was given 100 kU dissolved in 5 mL normal saline with slowly injection every 3 h until 24 h after recovery (no drug was given at 24 h). In the control group, 5 mL normal saline was given with same delivery time and frequency as that in the UTI group. The venous blood of the pigs was collected at VF, 2, 4, 6, 12, and 24 h after ROCS, and tumor necrosis factor -α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) were measured by enzyme-linked immunosorbent assay (ELISA) method. Because IMA was sensitive and increased rapidly, venous blood was detected at 1 h after ROSC, and the rest test time were same with the rest of the blood factors. Statistical analysis was performed using LSD-t test and variance analysis. The pigs were sacrificed 24 h after ROSC, and specimens from heart tissue were taken for HE staining. Results Before ventricular fibrillation in three groups, there was no significant difference in serum levels of inflammatory cytokines, oxidative stress indexes, and myocardial ischemia markers between the two groups (P>0.05). At 2 h after ventricular fibrillation, the levels of TNF-α and IL-6 level in the UTI group was significantly lower than those in the control group. At 4 h, MDA level in the UTI group was significantly lower than that in the control group (P 0.05). HE staining results showed that the damage degree of myocardial tissue in the UTI group was significantly lower than that in the control group at 24 h after ROSC. Conclusions UTI can significantly antagonize inflammatory response, reduce oxidative stress, and improve the myocardial tissue injury after resuscitation. It can protect myocardial injury after cardiopulmonary resuscitation. Key words: Ulinastatin; Cardiopulmonary resuscitation; Post-cardiac arrest syndrome; Tumor necrosis factor -αInterleukin-6; Superoxide dismutase; Ischemia modified albumin