Antegrade flow and peripheral resistance determine the level of endogenous arteriogenesis in patients with superficial femoral artery occlusion.

OBJECTIVES: Occlusion in a limb artery leads to impaired blood supply and ischaemia. Collateral artery growth (arteriogenesis) is one of the most effective natural response mechanisms to compensate this pathologic situation. However, it is unknown if clinically important features, like poor run-off, have an impact on compensatory vessel growth. METHODS: Study population of this retrospective study consisted of 70 patients who suffered from lower limb ischaemia and underwent bypass surgery because of an occlusion of the superficial femoral artery. Clinical data were collected and pre- and postoperative angiograms were reviewed. Number of collateral vessels bypassing the occluded segment was counted. Features of inflow and outflow vessels were recorded. RESULTS: The mean number of collaterals was 13 + or - 0.5 per patient. In univariate analysis, short daily walking distance, chronic critical leg ischaemia, low ankle brachial index, low number of patent calf arteries and stenosed inflow arteries predicted low number of collateral arteries. In the multivariate analysis, only the quality of inflow and the number of patent calf vessels demonstrated an independent association (P < 0.05) with the number of collaterals. CONCLUSIONS: Ankle-brachial index, grade of symptoms and daily walking capacity could be used to predict collateral density. Importantly, a good antegrade flow and peripheral runoff seem to have a significant effect on collateral density, implying an impact on the activation of arteriogenesis.

Gene therapy for therapeutic angiogenesis in critically ischaemic lower limb - on the way to the clinic.

Currently, no effective pharmacological treatment is available for vascularisation defects in lower limbs. Many patients presenting with persistent pain and ischaemic ulcers are not suitable candidates for surgical or endovascular approaches. Further refinement of the available methods will undoubtedly lead to a more active approach towards treatment of peripheral arterial occlusive disease (PAOD). Recently, therapeutic angiogenesis, in the form of recombinant growth factor administration or gene therapy, has emerged as a novel tool to treat these patients. However, improved gene transfer methods and better understanding of blood vessel formation are required to bring therapeutic angiogenesis to clinical practice. Here we review the clinical problem (PAOD), mechanisms of blood vessel formation (angiogenesis, vasculogenesis and arteriogenesis), experimental evidence and clinical trials for therapeutic angiogenesis in critically ischaemic lower limbs. Also, angiogenic growth factors, including vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs), delivery methods, and vectors for gene transfer in skeletal muscle, are discussed. In addition to vascular growth, gene transfer of growth factors may enhance regeneration, survival, and innervation of ischaemic skeletal muscle. Nitric oxide (NO) appears to be a key mediator in vascular homeostasis and growth, and a reduction in its production by age, hypercholesterolemia or diabetes leads to the impairment of ischaemic disorders.

Complications after treatment of proximal femoral fractures.

BACKGROUND AND AIMS: The number of fractures of the proximal femur is increasing faster than the number of elderly people. The aim of the study was to record all complications after operative treatment of proximal femoral fractures in order to reduce the incidence of these complications in the future. MATERIAL AND METHODS: The files of 334 patients with proximal femoral fractures were retrospectively analyzed. The number of all general and operative complications were recorded. RESULTS AND CONCLUSIONS: The primary mortality was 8 percent. The most common general complication was a thromboembolic one. Local complications were recorded in 66 cases. Thirty-eight percent of femoral neck fractures treated by internal fixation were complicated. Increased attention should be focused on the sufficient antithrombosis prophylaxis, which should be continued at least during the whole convalescence period at the hospital. It remains to be clarified, if improved technical skill may improve the results of femoral neck osteosynthesis, which in this group of patients appeared far from satisfactory. The development of post-operative care and selection of right patients to an appropriate rehabilitation program is perhaps the most important factor today, in order to reduce complications in general.

The effects of guanfacine, alpha-2 agonist, on the performance of young and aged rats in spatial navigation task.

The aim of the present experiment was to study the effects of a low dose (0.001 mg/kg) of guanfacine, alpha-2 agonist, on the acquisition and retention of a water maze task measuring spatial reference memory in young and aged rats. Aged rats were impaired in the acquisition of this task. Both young and aged rats treated with guanfacine had shorter escape latencies than their saline treated counterparts. However, guanfacine treatment increased the speed of swimming in aged rats. According to the results of the probe trial, guanfacine may slightly improve the acquisition/retention of water maze task in young rats, whereas it may slightly impair the acquisition/retention of aged rats. The results suggest that a low dose of guanfacine administered peripherally may have different effects on young and aged rats in water maze performance, and a low dose of guanfacine does not improve spatial reference memory in aged rats.

Clinical applications of vascular gene therapy.

Despite significant advances in prevention, coronary artery disease remains the leading cause of death in the Western world. Surgical bypass and angioplasty are the primary interventional therapies but they are limited by the problems of restenosis and graft occlusions. Natural response to vascular occlusion involves the formation of collateral vessels that bypass obstructions, but they are often inefficient in relieving ischemia. Vascular gene transfer offers a promising new approach to solve these problems. Its potential has been shown in animal models and in first human trials using vascular endothelial growth factor, fibroblast growth factor, and E2F cell-cycle transcription factor decoy. However, further basic research on gene transfer vectors, gene delivery techniques, and identification of effective treatment genes is needed to improve the efficacy and safety of human vascular gene therapy.