Objective: To evaluate the effects of ulinastatin (UTI) on improving inflammatory response and myocardial and lung tissue injury after cardiopulmonary resuscitation (CPR) in porcine model.
Methods: Ventricular fibrillation (VF) was induced in 20 female pigs by programmed stimulation method. CPR was begun 8 minutes after VF. Pigs with recovery of spontaneous circulation (ROSC) were randomly divided into two groups: group UTI, UTI was given immediately after resuscitation, with 100 kU dissolved in 5 ml of normal saline by slow intravenous injection every 3 hours, up to 24 hours after resuscitation. In control group, 5 ml of normal saline was given with same delivery time and frequency as that in the UTI group. Before VF, immediately after ROSC, 3 hours, 12 hours and 24 hours after ROSC, samples of venous blood were collected for examination of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), using the enzyme-linked immunospecific assay (ELISA) method. The pigs were sacrificed at 24 hours after ROSC for myocardium and lung pathological and ultrastructural examinations.
Results: Among a total of 20 domestic pigs, 15 pigs were successfully resuscitated after 8-minute VF. Eight pigs in UTI group and 7 pigs in control group survived for 24 hours. Pro-inflammatory factors of the both groups were increased gradually after ROSC. Levels of TNF-α, IL-1β, ICAM-1 and VCAM-1 were not significant different between UTI and control groups before VF and immediately after ROSC. But TNF-α and IL-1β levels were significantly lower in the UTI group than those of the control group beginning from 3 hours after ROSC (TNF-α: 28.79±9.49 ng/L vs. 44.01±17.01 ng/L, IL-1β: 153.50±67.47 ng/L vs. 252.09±80.41 ng/L, both P<0.05); ICAM-1 and VCAM-1 levels were significantly lower in the UTI group than those of the control group from 12 hours after ROSC (ICAM-1: 11.05±5.11 μg/L vs. 17.09±5.69 μg/L, VCAM-1: 11.17±4.75 μg/L vs. 16.62±4.63 μg/L, both P<0.05). The myocardium and lung injuries at 24 hours after ROSC were significantly milder in UTI group than that of the control group.
Conclusion: UTI can significantly reduce the pro-inflammatory reaction and the extent of myocardial and lung tissue injury after resuscitation.