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Articular chondrocytes exist in an environment lacking in oxygen and nutrients due to the avascular nature of cartilage. The main source of metabolic energy is glucose, which is taken up by glucose transporters (GLUTs). In diseased joints, oxygen tensions and glucose availability alter as a result of inflammation and changes in vascularisation. Accordingly, in this study we examined the effects of hypoxia and the hypoxia mimetic cobalt chloride (CoCl 2 ) on glucose transport in equine chondrocytes and compared expression of the hypoxia responsive GLUT1 gene in normal and diseased cartilage. Monolayers of equine chondrocytes were exposed to 20% O 2 , 1% O 2 , CoCl 2 (75 mM), or a combination of 1% O 2 and CoCl 2 . Glucose uptake was measured using 2-deoxy-D-[2,6-3 H] glucose. GLUT1 protein and mRNA expression were determined by FACS analysis and qPCR, respectively. GLUT1 mRNA expression in normal and diseased cartilage was analyzed using explants derived from normal, OA, and OCD cartilage. Chondrocytes under hypoxic conditions exhibited a significantly increased glucose uptake as well as upregulated GLUT1 protein expression. GLUT1 mRNA expression significantly increased in combined hypoxia-CoCl 2 treatment. Analysis of clinical samples indicated a significant reduction in GLUT1 mRNA in OA samples. In OCD samples GLUT1 expression also decreased but did not reach statistical significance. The increase in glucose uptake and GLUT1 expression under hypoxic conditions confirms that hypoxia alters the metabolic requirements of chondrocytes. The altered GLUT1 mRNA expression in diseased cartilage with significance in OA suggests that reduced GLUT1 may contribute to the failure of OA cartilage repair. ß

Ischaemic preconditioning is a process by which exposure of a tissue to a short period of non-damaging ischaemic stress leads to resistance to the deleterious effects of a subsequent prolonged ischaemic stress. It has been extensively described in the heart, but few studies have examined the possibility that it can occur in skeletal muscle. We have used a rat model of ischaemia of one limb to examine this possibility. Exposure of the hind limb to a period of ischaemia of five minutes and reperfusion for five minutes significantly protected the tibialis anterior muscle against the structural damage induced by a subsequent period of limb ischaemia for four hours and reperfusion for one hour. This protection was evident on examination of the muscle by both light and electron microscopy. Longer or shorter times of prior ischaemia had no effect.

Gastrointestinal complications following cardiopulmonary bypass (CPB) are relatively uncommon, but are associated with a high mortality rate. Impairment of bowel perfusion during and following CPB may serve as a trigger for the development of multiorgan failure. The aim of our study was the development of a new animal model allowing quantitative analysis of small bowel microcirculation during and after CPB. Twelve Landrace pigs served as laboratory animals. A 15-cm loop of the terminal ileum was exteriorized for microscopic observation. In 6 animals, a normothermic, partial left heart bypass (pLHB) was established for 2 h with a flow rate of 2,000 ml/min. Arterioles, collecting venules and the capillaries of the small bowel were recorded for the analysis of the microcirculation. All parameters were recorded prior to, during pLHB and up to 2 h after weaning off the bypass. Six sham operated animals served as controls. Despite unchanged hemodynamics, pLHB leads to microvascular perfusion disturbances of the small bowel. In pLHB animals, blood cell velocity in postcapillary venules (30–70 µm) was significantly decreased during and following bypass. Capillary density was also reduced during bypass and decreased even further after pLHB to only 30% of the control values. With this new large animal model for quantitative assessment of microvascular perfusion of the small bowel during CPB, it could be clearly demonstrated that partial normothermic left heart bypass leads to a significant disturbance of the small bowel microcirculation even under stable hemodynamic conditions.

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