β(2)-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats

Abstract

Early hyperglycemia after trauma increases morbidity and mortality. Insulin is widely used to control posttrauma glucose, but this treatment increases the risk of hypoglycemia. We tested a novel method for early posttrauma hyperglycemia control by suppressing hepatic glycogenolysis via β2-adrenoreceptor blockade [ICI-118551 (ICI)]. We have shown that, after severe trauma, obese Zucker (OZ) rats, similar to obese patients, exhibit increased acute lung injury compared with lean Zucker (LZ) rats. We hypothesized that OZ rats exhibit a greater increase in early posttrauma glucose compared with LZ rats, with the increased posttrauma hyperglycemia suppressed by ICI treatment. Orthopedic trauma was applied to both hindlimbs in LZ and OZ rats. Fasting plasma glucose was then monitored for 6 h with or without ICI (0.2 mg·kg(-1)·h(-1) iv.) treatment. One day after trauma, plasma IL-6 levels, lung neutrophil numbers, myeloperoxidase (MPO) activity, and wet-to-dry weight ratios were measured. Trauma induced rapid hepatic glycogenolysis, as evidenced by decreased liver glycogen levels, and this was inhibited by ICI treatment. Compared with LZ rats, OZ rats exhibited higher posttrauma glucose, IL-6, lung neutrophil infiltration, and MPO activity. Lung wet-to-dry weight ratios were increased in OZ rats but not in LZ rats. ICI treatment reduced the early hyperglycemia, lung neutrophil retention, MPO activity, and wet-to-dry weight ratio in OZ rats to levels comparable with those seen in LZ rats, with no effect on blood pressure or heart rate. These results demonstrate that β2-adrenoreceptor blockade effectively reduces the early posttrauma hyperglycemia, which is associated with decreased lung injury in OZ rats.

Keywords: glucose; lung injury; obesity; trauma; β2-adrenoreceptor.

Fig. 1.

A: glucose curve in lean Zucker (LZ) and obese Zucker (OZ) rats with or without [ICI-118551 (ICI)] treatment within 6 h after trauma. B0 is the basal level before ICI or saline infusion, and B1 is the basal level before trauma. n ≥ 6 for each group. *P < 0.05, LZ vs. OZ rats; #P < 0.05, LZ vs. LZ + ICI rats; +P < 0.05, OZ vs. OZ + ICI rats. B: liver glycogen levels 6 h after trauma in LZ and OZ rats with or without ICI treatment. n = 5 for each group. *P < 0.05, trauma vs. control or ICI.

Fig. 2.

A and B: blood pressure (Bp; A) and heart rate (B) in LZ and OZ rats within 6 h after trauma with or without ICI treatment. B0 is the basal level before ICI or saline infusion, and B1 is the basal level before trauma. n ≥ 5 for each group. *P < 0.05, LZ vs. OZ rats; +P < 0.05 vs. B1 in all groups.

Fig. 3.

A: cortisol levels before and 1 h after trauma in LZ and OZ rats. n = 6 for each group. *P < 0.05, trauma vs. basal. B: plasma insulin levels in 6 h after trauma in LZ and OZ rats. n = 6 for each group. *P < 0.01, LZ vs. OZ rats. C: glucagon levels 6 h after trauma in LZ and OZ rats. n = 6 for each group. *P < 0.05 vs. LZ or OZ rats with 6 h after trauma.

Fig. 4.

A: IL-6 levels 1 day after trauma. n ≥ 6 for each group. *P < 0.05 vs. LZ rats with trauma; +P < 0.01 vs. control. B: wet-to-dry weight ratio 1 day after trauma. n ≥ 6 for each group. *P < 0.05 vs. control. C: lung neutrophil numbers 1 day after trauma. n ≥ 5 for each group. *P < 0.01 vs. LZ rats with trauma; +P < 0.01 vs. control; #P < 0.01, trauma vs. ICI within OZ rats. D: lung myeloperoxidase (MPO) activities 1 day after trauma. n ≥ 5 for each group. *P < 0.05 vs. LZ rats with trauma; +P < 0.05 vs. control.