• A new model of peripheral arterial disease: sustained impairment of nutritive microcirculation and its recovery by chronic electrical stimulation.

      Brown, Margaret D.; Kelsall, C.J.; Milkiewicz, M.; Anderson, Stephen I.; Hudlicka, Olga (Taylor & Francis (Informa Healthcare), 2005)
      OBJECTIVES: To develop a model of peripheral arterial disease (PAD) in rat skeletal muscle with sustained impairment of microcirculatory perfusion, and to ascertain whether increased muscle activity can reverse the impairment. METHODS: Three weeks after iliac ligation in rats, the ipsilateral femoral artery was ligated (double ligation, DL), and in some animals, muscle activity was increased by electrical stimulation for 2 weeks (10 Hz, 15 min on, 85 mins off, 7 times per day). Diameter changes of precapillary arterioles to vasoactive agonists and capillary perfusion (flow intermittency, capillary red cell velocity [V(rbc)], and diameters) were measured in extensor digitorum longus muscle and compared with 5 weeks iliac only ligation (single ligation, SL) and controls. Total muscle endothelial nitric oxide synthase (eNOS) was estimated by Western blotting. RESULTS: Whereas single ligation increased intermittency of capillary flow with little effect on V(rbc) and shear stress, DL completely eliminated increases in V(rbc) and shear stress after muscle contractions. Arterial dilation to sodium nitroprusside was attenuated similarly in SL and DL; in SL, acetylcholine induced constriction and bradykinin an attenuated dilation, but in DL vessels were unresponsive to either. Chronic stimulation returned all microcirculatory parameters in DL to normal and increased levels of eNOS protein by 75%. CONCLUSIONS: Femoral artery ligation following iliac ligation impairs arteriolar vasodilator capacity, capillary perfusion, and shear-dependent function of microcirculatory endothelium more than iliac ligation alone and is more representative of long-standing ischemia in PAD. Chronic intermittent electrical stimulation can normalize these derangements.
    • ICAM-1 expression and leukocyte behavior in the microcirculation of chronically ischemic rat skeletal muscles.

      Anderson, Stephen I.; Shiner, Ruth; Brown, Margaret D.; Hudlicka, Olga (Elsevier, 2006)
      In muscle microcirculation, short periods of ischemia followed by reperfusion are known to upregulate leukocyte and endothelial adhesion molecules, but little is known about leukocyte adherence and ICAM-1 expression during chronic ischemia or any likely effect of muscle activity which is recommended in chronic ischemia due to peripheral arterial disease. Leukocyte rolling and stationary adhesion were observed in post-capillary venules in ischemic and contralateral rat extensor digitorum longus (EDL) muscles 3 and 7 days after unilateral ligation of the common iliac artery and in 3-day ischemic EDLs that were electrically stimulated on days 1 and 2 post-ligation (7 x 15 min per day). ICAM-1 was localized immunohistochemically to venular vessels in all muscles. Following ligation, use of the ischemic leg was observed to be restricted for the first 3 days, returning to normal by 7 days. After 3 days, leukocyte rolling/adherence and ICAM-1 expression were no different in ischemic than control muscles, but all were increased in contralateral muscles. In ischemic muscles, electrical stimulation doubled the numbers of rolling leukocytes and upregulated ICAM-1 expression. After 7 days, increased muscle activity as a result of natural movement also resulted in greater ICAM-1 expression, a 4- to 5-fold increase in rolling leukocyte numbers and a 3-fold increase in stationary adherent leukocytes. Chronic ischemia thus increases ICAM-1 and leukocyte adherence in muscle microcirculation only when combined with contractile activity. Post-capillary venular endothelium may be modified by muscle acidosis when contractions are performed under low flow conditions or by changes in rheological (shear force) factors.
    • Nutrition and immunity in perinatal hypoxic-ischemic injury

      Gandecha, H; Kaur, A; Sanghera, R; Preece, J; Pillay, Thillagavathie; Department of Neonatology, University Hospitals Leicester NHS Trust, Leicester LE1 5WW, UK. (MDPI, 2022-07-01)
      Perinatal hypoxia ischaemia (PHI), acute and chronic, may be associated with considerable adverse outcomes in the foetus and neonate. The molecular and cellular mechanisms of injury and repair associated with PHI in the perinate are not completely understood. Increasing evidence is mounting for the role of nutrients and bioactive food components in immune development, function and repair in PHI. In this review, we explore current concepts around the neonatal immune response to PHI with a specific emphasis on the impact of nutrition in the mother, foetus and neonate.