Objective— The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. Methods and Results— Lymphocytes, detected with markers for NK1.1, CD3, and CD4, invaded the collateral vessel wall. Arteriogenesis was impaired in C57BL/6 mice depleted for Natural Killer (NK)-cells by anti-NK1.1 antibodies and in NK-cell–deficient transgenic mice. Arteriogenesis was, however, unaffected in Jα281-knockout mice that lack NK1.1 ⁺ Natural Killer T (NKT)-cells, indicating that NK-cells, rather than NKT-cells, are involved in arteriogenesis. Furthermore, arteriogenesis was impaired in C57BL/6 mice depleted for CD4 ⁺ T-lymphocytes by anti-CD4 antibodies, and in major histocompatibility complex (MHC)-class-II–deficient mice that more selectively lack mature peripheral CD4 ⁺ T-lymphocytes. This impairment was even more profound in anti-NK1.1-treated MHC-class-II–deficient mice that lack both NK- and CD4 ⁺ T-lymphocytes. Finally, collateral growth was severely reduced in BALB/c as compared with C57BL/6 mice, 2 strains with different bias in immune responsiveness. Conclusions— These data show that both NK-cells and CD4 ⁺ T-cells modulate arteriogenesis. Promoting lymphocyte activation may represent a promising method to treat ischemic disease.

Objective— Because late vein graft failure is caused by intimal hyperplasia (IH) and accelerated atherosclerosis, and these processes are thought to be inflammation driven, influx of monocytes is one of the first phenomena seen in IH, we would like to provide direct evidence for a role of the MCP-1 pathway in the development of vein graft disease. Methods and Results— MCP-1 expression is demonstrated in various stages of vein graft disease in a murine model in which venous interpositions are placed in the carotid arteries of hypercholesterolemic ApoE3Leiden mice and in cultured human saphenous vein (HSV) segments in which IH occurs. The functional involvement of MCP-1 in vein graft remodeling is demonstrated by blocking the MCP-1 receptor CCR-2 using 7ND-MCP-1. 7ND-MCP1 gene transfer resulted in 51% reduction in IH in the mouse model, when compared with controls. In HSV cultures neointima formation was inhibited by 53%. In addition, we demonstrate a direct inhibitory effect of 7ND-MCP-1 on the proliferation of smooth muscle cell (SMC) in HSV cultures and in SMC cell cultures. Conclusion— These data, for the first time, prove that MCP-1 has a pivotal role in vein graft thickening due to intimal hyperplasia and accelerated atherosclerosis.

Postoperative ileus is a common complication of abdominal surgery, leading to patient discomfort, morbidity and prolonged postoperative length of hospital stay (LOS). Previous studies suggested that chewing gum stimulates bowel function after abdominal surgery, but were underpowered to evaluate its effect on LOS and did not include enhanced recovery after surgery (ERAS)-based perioperative care. This study evaluated whether chewing gum after elective abdominal surgery reduces LOS and time to bowel recovery in the setting of ERAS-based perioperative care. A multicentre RCT was performed of patients over 18 years of age undergoing abdominal surgery in 12 hospitals. Standard postoperative care (control group) was compared with chewing gum three times a day for 30 min in addition to standard postoperative care. Randomization was computer-generated; allocation was concealed. The primary outcome was postoperative LOS. Secondary outcomes were time to bowel recovery and 30-day complications. Between 2011 to 2015, 1000 patients were assigned to chewing gum and 1000 to the control arm. Median LOS did not differ: 7 days in both arms (P = 0·364). Neither was any difference found in time to flatus (24 h in control group versus 23 h with chewing gum; P = 0·873) or time to defaecation (60 versus 52 h respectively; P = 0·562). The rate of 30-day complications was not significantly different either. The addition of chewing gum to an ERAS postoperative care pathway after elective abdominal surgery does not reduce the LOS, time to bowel recovery or the rate of postoperative complications. Registration number: NTR2594 (Netherlands Trial Register).