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Fig. 1 | Critical Care

Fig. 1

From: Icatibant as an early rescue therapy in hypovolemic shock with converting enzyme inhibitor treatment

Fig. 1

a Protocol design. b Survival curve in volume-targeted hemorrhagic shock. Hemorrhagic shock was induced with the same protocol as previously described [4]. In this study, the main difference was the withdrawn volume of blood (0.6 ml vs 0.3 ml) to induce volume-targeted hemorrhagic shock. Briefly, the animals were anesthetized with ketamine and xylazine and intubated using an intratracheal cannula. The left jugular vein and femoral artery were catheterized, and ketamine was continuously infused until the end of the shock procedure. A volume of 0.6 ml of blood was withdrawn through the femoral arterial line in order to induce hemorrhagic shock. The blood was re-infused at the end of the 2-h period of shock with the addition of an equal volume of lactated Ringer’s solution to ensure appropriate fluid volume restoration. The mice were sacrificed 1 h after the shock procedure. An ACEI (ramipril) was given at a dose of 1 mg/kg per day in drinking water (at a concentration of 5 μg/ml) during the 7 days prior to shock. Icatibant was subcutaneously administered at a dose of 250 μg/kg at the same time as anesthesia. Control, control shocked mice; ACEI, shocked mice treated with angiotensin-converting enzyme inhibitor; ACEI + icatibant, shocked mice treated with both ACEIs and a single injection of icatibant at the same time as the administration of anesthesia. N = 11 per group. Qualitative variables were described using the median (25–75% interquartile range). Comparisons between groups were performed using the nonparametric Kruskal–Wallis one-way analysis of variance followed by the post hoc Dunn’s test. Survival curves were computed according to Kaplan–Meier and compared with the log-rank test. Analyses were performed using GraphPad Prism 4 (GraphPad Software Inc., San Diego, CA, USA). Survival in both ACEI + icatibant and control groups was significantly higher than in the ACEI group (p < 0.01)

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