Dose effects of recombinant human IL-11 on the systemic hemodynamic function in hemorrhagic shock

Introduction

We have previously demonstrated that administration of recombinant human IL-11 (rhIL-11) during resuscitation improves the cardiovascular functions in a rodent model of hemorrhagic shock. The purpose of this study was to elucidate: (1) whether these beneficial effects were dose related, and (2) whether the effects of rhIL-11 could be reproduced in a large animal model.

Methods

Swine (n = 56, weight = 25–35 kg) underwent 40% blood volume hemorrhage, and a 1-hour shock period, followed by resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive: (1) group I, 5 μg/kg rhIL-11 (n = 6); group II, 20 μg/kg rhIL-11 (n = 5); group III, 50 μg/kg rhIL-11 (n = 6) – and then, (2) group IV, sham hemorrhage (sham, n = 10); group V, sham hemorrhage and 50 μg/kg rhIL-11 (sham + IL-11, n = 6); group VI, no drug (saline, n = 15); group VII, 50 μg/kg rhIL-11 (IL-11, n = 14). Blood samples and urine were obtained and analyzed at baseline, the end of hemorrhage, and at every hour.

Results

(1) The mean arterial pressure was higher post-resuscitation (PR) in group III (62.9 ± 8.2 mmHg) than in groups I and II (54.9 ± 1.7, 53.9 ± 4.3 mmHg; P < 0.01). The urine output (I: 999 ± 428, II: 1,249 ± 180, III: 1,434 ± 325 ml) and the cardiac output (CO) (I: 3.01 ± 0.66, II: 3.30 ± 0.49, III: 3.43 ± 0.57 l/min) increased dose dependently. The volume of third space fluid loss of group III decreased significantly (I: 157 ± 32, II: 138 ± 32, III: 82 ± 21 ml; P < 0.05). (2) Mean arterial pressure was higher PR among groups IV, V and VII (71.4 ± 7.5, 71.0 ± 8.9, 72.9 ± 12.3 mmHg) compared with group VI (59.9 ± 10.9) and CO of PR was higher in group VII (3.46 ± 0.56 l/min) than group IV (2.99 ± 0.62; P < 0.01). Following resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group VII (1,434 ± 325 ml, 1.0035, 82 ± 21 ml) compared with group VI (958 ± 390 ml, 1.0053, 125 ± 32 ml; P < 0.05).

Conclusion

The effects of rhIL-11 on the cardiovascular functions were influenced by the dose of rhIL-11, although the relationship did not follow simple linearity. A 50 μg/kg dose rhIL-11 significantly improves cardiovascular functions in a porcine model of hemorrhagic shock.