Effects of verapamil on intestinal injury in a rat model of acute mesenteric ischemia

Abstract

Background

Acute mesenteric ischemia (AMI) is a surgical emergency requiring prompt revascularization with resection of unsalvageable bowel. Despite successful revascularization, ongoing organ damage can persist from ischemia-reperfusion injury (IRI) and there is a need for adjunct therapies to ameliorate this ongoing insult.

Materials and methods

Sprague-Dawley rats (n = 36) were divided into five groups: control, heparin (HEP), HEP + verapamil (VER), HEP + valproic acid (VPA), HEP+VER+VPA. The animals were subjected to 45 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Upon reperfusion, therapies were administered. Plasma samples were collected before occlusion and at end-of-study for intestinal fatty acid binding protein (I-FABP) and pro-inflammatory cytokines. The full length of the small intestine was collected, stained with H&E and scored according to the Park/Chiu score for intestinal ischemia damage.

Results

Twenty-three of 36 rats survived 4 h of reperfusion and there was no difference in survival between the groups. I-FABP levels was significantly lower in HEP+VER vs. control (3.8 ± 1.5 vs. 6.18 ± 1.0ng/ml; p = 0.0040). IL-1beta, IL-6 and TNF-alpha showed the lowest mean values in the HEP+VER group compared to all groups. The histological analysis revealed the lowest score of intestinal damage in the HEP+VER group, however, the difference to control was not significant.

Conclusion

Administering heparin and verapamil at the time of revascularization may mitigate intestinal IRI without causing detrimental systemic effects. Further studies in large animal models and in the setting of local administration are needed to investigate the potential of this approach.