The effect of post-reperfusion levosimendan in an experimental intestinal ischemia-reperfusion model

Abstract

Background: Levosimendan has been reported to have a positive effect on ischemia-reperfusion injury. Herein, we aimed to evaluate the effects of levosimendan applied after reperfusion in an experimental intestinal injury-reperfusion (IR) model.

Methods: Twenty-one Wistar-albino male rats were separated into three groups: Sham group (n = 7): solely superior mesenteric artery (SMA) was dissected after laparotomy; intestinal ischemia-reperfusion group (IIR, n = 7): SMA was clamped for 60 min and unclamped for 120 min to cause ischemia-reperfusion; IIR + levosimendan group (IIR + L, n = 7): levosimendan was administered in ischemia-reperfusion model. The mean arterial pressures (MAP) were measured in all groups. MAP measurements were performed at the end of stabilization, at the 15th, 30th, and 60th minute of ischemia; at the 15th, 30th, 60th, and 120th minute of reperfusion; and at the end of levosimendan bolus application and when levosimendan infusion concluded. Reperfusion injury was evaluated with tissue malondialdehyde (MDA) and by Chiu score.

Results: MAP at 15 min, 30 min, and 60 min of reperfusion was lower in IIR and IIR + L groups compared with basal inter-group measurements. Decline in MAP at 30 min after reperfusion was statistically significant in IIR and IIR + L groups when compared with the sham group. There was no significant difference between MDA levels in the groups. Chiu score was significantly lower in the sham group when compared to IIR and IIR + L groups and higher in IIR when compared to the IIR + L group.

Conclusion: Levosimendan leads to a decrease in intestinal damage although it did not affect lipid peroxidation and MAP when administered after reperfusion in an experimental intestinal IR model.

Keywords: Ischemia; Mesenteric vascular occlusion; Phosphodiesterase 3 inhibitors; Rats; Reperfusion; Simendan.

Fig. 1

Study groups flow chart. ^*IIR intestinal ischemia-reperfusion, ^†IIR + L intestinal ischemia-reperfusion + levosimendan

Fig. 2

Small intestinal tissue following ischemia and reperfusion

Fig. 3

Mean arterial blood pressure levels. *Comparison of IIR and IIR + L groups with sham group (p = 0.011, p = 0.011). ^&IIR + L group, group measurements when compared to basal measurements (p < 0.001). ^†IIR group, group measurements when compared to basal measurements (p < 0.001). IIR intestinal ischemia-reperfusion, IIR + L intestinal ischemia-reperfusion + levosimendan, MAP mean arterial blood pressure, MAP0 basal time, MAP1 15th min of ischemia, MAP2 30th min of ischemia, MAP3 60th min of ischemia, MAP4 15th min of reperfusion, MAP5 30th min of reperfusion, MAP6 60th min of reperfusion, MAP7 120th min of reperfusion, MAP8 after levosimendan bolus, MAP9 at the end of the levosimendan infusion

Fig. 4

Tissue Malondialdehid (MDA) levels in small intestinal tissue (p > 0.05)

Fig. 5

Histopathological evaluation of the small intestinal tissue. *Comparison of the IIR and IIR + L groups with the Sham group (p = 0.001). **Comparison of the IIR + L group with the IIR group (p = 0.03). IIR intestinal ischemia-reperfusion, IIR + L intestinal ischemia-reperfusion + levosimendan

Fig. 6

Microscopic view of the Sham group tissue samples. Normal small intestinal mucosa: plica circularis (triangle), epithelial layer (e), goblet cells (right arrow), submucosal layer (star), and tunica muscularis (square). Hematoxylin–eosin (H&E) stain with amplifications of A1: × 4, A2: × 10, A3: × 20, and A4: × 40)

Fig. 7

Microscopic view of IIR group tissue samples. Villus degeneration, increase in capillary permeability and congestion (right arrow), increase in mononuclear cells, intraepithelial hemorrhage, and ulcers are observed, and degeneration is observed in the plica circularis and epithelial layers (star) and shows the submucosal layer and the tunica muscularis (square). Hematoxylin–eosin (H&E) stain with amplifications of B1: × 4, B2: × 10, B3: × 20, B4: × 40)

Fig. 8

Microscopic view of the IIR + L group tissue samples. Epithelial layer (e), submucosal layer (black star), tunica muscularis (square), and goblet cells (right arrow) are shown. Hematoxylin–eosin (H&E) stain with amplifications of C1: × 4, C2: × 10, C3: × 20, C4: × 40)