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Endothelial progenitor cells (EPCs) are a group of heterogeneous cells in bone marrow (BM) and blood. Ischaemia increases reactive oxygen species (ROS) production that regulates EPC number and function. The present study was conducted to determine if ischaemia‐induced ROS differentially regulated individual EPC subpopulations using a mouse model concomitantly overexpressing superoxide dismutase (SOD)1, SOD3 and glutathione peroxidase. Limb ischaemia was induced by femoral artery ligation in male transgenic mice with their wild‐type littermate as control. BM and blood cells were collected for EPCs analysis and mononuclear cell intracellular ROS production, apoptosis and proliferation at baseline, day 3 and day 21 after ischaemia. Cells positive for c‐Kit+/CD31+ or Sca‐1+/Flk‐1+ or CD34+/CD133+ or CD34+/Flk‐1+ were identified as EPCs. ischaemia significantly increased ROS production and cell apoptosis and decreased proliferation of circulating and BM mononuclear cells and increased BM and circulating EPCs levels. Overexpression of triple antioxidant enzymes effectively prevented ischaemia‐induced ROS production with significantly decreased cell apoptosis and preserved proliferation and significantly increased circulating EPCs level without significant changes in BM EPC populations, associated with enhanced recovery of blood flow and function of the ischemic limb. These data suggested that ischaemia‐induced ROS was differentially involved in the regulation of circulating EPC population.

The aim of the present study was to establish the changes in nerve excitability and symptom generation associated with the application of focal nerve compression (FNC). FNC was applied at the wrist by means of a custom-designed electrode in 10 healthy subjects, and was maintained for 24 min. Symptoms of paraesthesiae and signs of numbness were recorded every 30 s. Despite apparently minimal changes in axonal threshold, FNC was associated with prolongation in latency by 14.5 ± 2.1% (P < 0.001) and reduction in compound sensory action potential (CSAP) amplitude by 34.3 ± 5.1% (P < 0.001), with two subjects developing conduction block. The reduction in CSAP was associated with abolition of superexcitability, and an increase in refractoriness of 295.2 ± 55.5% (P < 0.005) and strength–duration time constant (SDTC) by 48.1 ± 10.3% (P < 0.005), all consistent with axonal depolarization. With release of FNC, threshold rapidly increased above pre-compression levels (P < 0.01), consistent with the development of axonal hyperpolarization. Associated with these changes in axonal excitability, paraesthesiae and numbness steadily increased throughout FNC and reached a peak at the termination of FNC, followed by a gradual recovery on release of FNC. When compared to previous studies that utilised the effects of more generalised limb ischaemia, the changes in axonal excitability recorded during FNC were qualitatively and quantitatively alike, suggesting that similar biophysical mechanisms contributed to the changes observed with both manoeuvres.

Bypass grafting to vessels beyond the popliteal bifurcation is an established method for treating severe limb ischaemia. Failure rate is high, however, especially when prosthetic vascular substitutes have to be used. When left in situ, saphenous vein can be used down to much smaller diameters than would be possible with reversed vein. With this method, vein utilization of around 90% can be achieved with respective increases in patency and limb salvage. Our early results with 26 in situ grafts are presented. In two cases the presence of a suitable tributary of the saphenous vein allowed a ‘bifurcated’ or ‘femorobitibial’ graft to be performed. All patients (17 males, nine females) were admitted with limb threatening ischaemia. Mean ankle pressure index was 0.29 (s.d. = 0.09), range 0.18–0.53. Average graft intra-operative flow rate measured 96 ml/min. Twenty grafts remain patent while six grafts have failed. In three of these failures, performed early in the series, the graft could not be made to function at the time of surgery. The mean postoperative ankle pressure index was 0.87 (s.d. = 0.19). Cumulative patency rate at 24 months in 74%. This rises to 83% if the three ‘on table’ failures are excluded. Five amputations were required; four as a result of graft failure and one despite a functioning graft. Four grafts clotted within 24 h but have remained patent following immediate thrombectomy. One patient required ligation of an arteriovenous fistula on the third postoperative day.

A 5 year retrospective review of blunt arterial injuries at the Royal Brisbane Hospital revealed that delay in diagnosis had catastrophic effects on limb survival. Only 17 of 23 patients with arterial injury were diagnosed at the time of admission. No record of symptoms of limb ischaemia was made in 13 patients and no signs recorded in five. Eight limbs required amputation. Improved results should follow more accurate diagnosis at the time of admission.

The effect of ischaemic limb injury on the turnover of noradrenaline in the hypothalamus and brain stem has been studied in rats. There are theoretical reasons for thinking that these regions are activated in trauma and previous work showed that during limb-ischaemia the concentration of noradrenaline in the hypothalamus decreased by 27 per cent. The tourniquets were applied to both hind-limbs 1 h after the injection of [14C]-tyrosine when the labelling of the noradrenaline was maximal. During 4 h limb ischaemia the endogenous tyrosine concentration in the plasma decreased while that in the hypothalamus first rose and then fell. Changes in a similar direction in the brain stem were not statistically significant. Limb ischaemia did not affect the decline in the specific activity of the plasma or tissue tyrosine. It was concluded that the injury increased the utilization of tyrosine by the body. During the 4 h bilateral hind-limb ischaemia the rate of decline of [14C]noradrenaline was significantly increased in the brain stem but not in the hypothalamus. Conditions in the brain stem were sufficiently close to ‘steady-state’ to be able to conclude that the injury increased the metabolism of noradrenaline in the brain stem. Conditions in the hypothalamus were too complicated for definite conclusions to be drawn. The possible reasons for this and the limitations of this method for studying noradrenaline turnover are discussed.

1. Shivering in response to changes in ambient or core temperature has been measured in control rats and rats injured by bilateral hind-limb ischaemia, both with and without fur. 2. Removal of the fur increased the threshold ambient temperature for the onset of shivering. 3. This threshold was lower than in uninjured controls during the latter half of a 4 hr period of bilateral hind-limb ischaemia in rats with or without fur. 4. The threshold was also lower than in uninjured controls after the period of bilateral hind-limb ischaemia but was not significantly different from that during the period of ischaemia. 5. The alterations in threshold were not accompanied by any significant changes in the slope of the regression line relating intensity of shivering and ambient temperature. 6. When the core temperature fell after limb ischaemia to levels which provoked shivering in uninjured controls, no shivering was seen in the injured rats. 7. These results are interpreted as further evidence for the lowering of the ‘set-point’ for thermogenesis after injury in the rat and are discussed in relation to the changes in body temperature after injury in that species.