Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy.
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Hepatocyte growth factor (HGF) exclusively stimulates the growth of endothelial cells without replication of vascular smooth muscle cells and acts as a survival factor against endothelial cell death. Therefore we hypothesized that a decrease in local vascular HGF might be related to the pathogenesis of peripheral arterial disease. We initially evaluated vascular HGF concentration in the vessels of patients with arteriosclerosis obliterans. Consistent with in vitro findings that hypoxia downregulated vascular HGF production, vascular HGF concentration in the diseased segments of vessels from patients with arteriosclerosis obliterans was significantly decreased as compared with disease-free segments from the same patients (P<0.05), accompanied by a marked reduction in HGF mRNA. On the other hand, a novel therapeutic strategy for ischemic diseases that uses angiogenic growth factors to expedite and/or augment collateral artery development has recently been proposed. Thus in view of the decreased endogenous vascular HGF, rhHGF (500 micrograms/animal) was intra-arterially administered through the internal iliac artery of rabbits in which the femoral artery was excised to induce unilateral hind limb ischemia, to evaluate the angiogenic activity of HGF, which could potentially have a beneficial effect in hypoxia. Administration of rhHGF twice on days 10 and 12 after surgery produced significant augmentation of collateral vessel development on day 30 in the ischemic model as assessed by angiography (P<0.01). Serial angiograms revealed progressive linear extension of collateral arteries from the origin stem artery to the distal point of the reconstituted parent vessel in HGF-treated animals. In addition, we examined the feasibility of intravenous administration of rhHGF in a moderate ischemia model. Importantly, intravenous administration of rhHGF also resulted in a significant increase in angiographic score as compared with vehicle (P<0.01). Overall, a decrease in vascular HGF might be related to the pathogenesis of peripheral arterial disease. In the presence of decreased endogenous HGF, administration of rhHGF induced therapeutic angiogenesis in the rabbit ischemic hind limb model, as potential cytokine supplement therapy for peripheral arterial disease. (+info)
Interleukin-10 (IL-10) augments allograft arterial disease: paradoxical effects of IL-10 in vivo.
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Interleukin-10 (IL-10) is an anti-inflammatory helper T cell type 2 (Th2) cytokine that modulates Th1-type cytokine production. Graft arterial disease (GAD) is a vascular obliterative process mediated via the Th1 cytokine interferon-gamma (IFN-gamma); allografts in IFN-gamma-deficient animals do not develop GAD. We investigated the effect of IL-10 and anti-IL-10 on GAD in murine heart transplants and whether anti-IL-10 reestablishes GAD in IFN-gamma-deficient hosts. Major histocompatibility complex class II-mismatched hearts were transplanted for 8 weeks into wild-type or IFN-gamma-deficient mice. In one set of experiments, wild-type hosts received daily administration of phosphate-buffered saline (PBS) or increasing IL-10; in a subsequent set of experiments, wild-type hosts received weekly PBS, rat IgG, or anti-IL-10 monoclonal antibody; IFN-gamma-deficient recipients received weekly PBS or anti-IL-10 monoclonal antibody. Explanted allografts were assessed for parenchymal rejection and GAD, cytokine profiles, and adhesion/costimulatory-molecule expression. Exogenous IL-10 resulted in increased Th2-like cytokine production; nevertheless, it exacerbated parenchymal rejection and GAD and increased CD8(+) infiltration. Anti-IL-10 did not significantly affect the extent of rejection or GAD, cytokine profiles, or immunohistology of the allografts in wild-type hosts. Adhesion molecule (CD54 and CD106) expression was not diminished by IL-10 treatment, and costimulatory-molecule (CD80 and CD86) expression was augmented by administration of exogenous IL-10. Allografts in IFN-gamma-deficient recipients showed mild rejection and no GAD, regardless of anti-IL-10 treatment. IL-10 in vivo thus has markedly different effects than predicted from in vitro experience. Although allografts develop Th2-like cytokine profiles treatment with IL-10 causes exacerbated rejection and GAD. (+info)
Ultrasonographic demonstration of manipulation-related aortic injuries after cardiac surgery.
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OBJECTIVES: This study was performed to evaluate the frequency and risk factors associated with new aortal lesions induced by surgical manipulation and their correlation with postoperative stroke. BACKGROUND: Little is known about the causative mechanism of intraoperative atheroembolism after cardiac surgery. METHODS: Epiaortic echocardiography was performed before cannulation and after decannulation in 472 patients undergoing cardiac surgery with extracorporeal circulation. RESULTS: A new lesion in the ascending aortal intima was identified in 16 patients (3.4%) after decannulation. New lesions were severe, with mobile lesions or disruption of the intima in 10 patients. Six of the severe lesions were related to aortic damping and the other four to aortic cannulation. Three patients in this group had postoperative stroke. Univariate analysis identified only the maximal thickness of the atheroma near the aorta manipulation site as a predictor of new lesions. The incidence of new lesions was 11.8% if the atheroma was approximately 3 to 4 mm thick and as high as 33.3% if the atheroma was >4 mm, but only 0.8% when it was <3 mm. Total 10 patients (2.1%) sustained neurological complications. Arteriosclerosis obliterans, atherosclerosis of the aorta and new mobile lesions were identified as predictors of strokes. CONCLUSIONS: This study demonstrated an association between new lesions created by surgical maneuvers and postoperative stroke. Embolic strokes were more likely to occur if new lesions were complicated with intimal disruption, especially of the mobile type. Modifications in surgical procedures will be needed if thick plaque (especially >4 mm) is noted near the manipulation site. (+info)
Postoperative delirium in patients with chronic lower limb ischaemia: what are the specific markers?
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OBJECTIVES: we determined the incidence and specific markers of postoperative delirium in elderly patients with chronic lower limb ischaemia. PATIENTS AND METHODS: since April, 1995, 110 patients aged 60 years or older (mean: 71.6+/-6.6 years) who underwent bypass surgery were assessed regarding aetiological factors of delirium: age, sex, dementia, body-mass index, hypertension, diabetes, cerebral disease, laboratory test results, severity of limb ischaemia, type of arterial occlusion, operative time, and blood transfusion. RESULTS: discriminant analysis showed statistical significance in the following five variables: age >/=70 years; critical limb ischaemia (and/or ankle pressure <40 mmHg); dementia; duration of operation >/=7 hours; low serum albumin. The overall percentage of cases correctly classified was 78.2% (Wilks>> Lambda=0.695, p<0.001); the standardized regression coefficients of the five variables were 0.648, 0.500, 0.329, 0.218, and 0.200, respectively. In logistic regression, the regression coefficients for old age and critical limb ischaemia were 2.646 (14.1 of odds ratio; 95% confidence interval, 2.7-72.0) and 1.337 (3.8; 1.3-10.9), respectively. CONCLUSIONS: the incidence of postoperative delirium in elderly patients with chronic lower-limb ischaemia was as high as 42.3%, and an age of over 70 years and critical limb ischaemia were identified as specific markers, with 14.1 times and 3.8 times the odds of suffering from delirium after bypass surgery. (+info)
Usefulness of the Symphony Nitinol Stent for arteriosclerosis obliterans.
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The Symphony Peripheral Stent is a self-expanding stent made of thermal memory Nitinol wire. Stents were implanted in 39 lesions of 32 patients (26 men, 6 women) with atherosclerosis obliterans (ASO). The ankle-arm index (AAI), and vessel diameters evaluated by quantitative angiography were compared before and 6 months after treatment. Symphony Peripheral Stent implantation significantly improved the AAI from 0.50+/-0.4 to 0.9+/-0.2 (p<0.01), the minimum lumen diameter (MLD) from 2+/-1.5 to 5+/-1.4 mm (p<0.01) and percent diameter stenosis (% DS) from 69+/-20% to 16.5+/-8% (p<0.01). Re-evaluation of 33 of the 39 lesions 6 months after treatment revealed a low restenosis rate of 15%, an AAI of 0.8+/-0.3, MLD of 4.5+/-2 mm and %DS of 30+/-22%, so the Symphony Peripheral Stent is thus a promising choice for patients with ASO. (+info)
Infrainguinal arterial reconstruction for limb salvage in patients with end-stage renal disease.
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OBJECTIVES: to evaluate the efficacy of infrainguinal bypass for limb-threatening ischaemia in patients with end-stage renal disease (ESRD). MATERIALS AND METHODS: from 1991 through 2000, 28 limbs in 22 patients with ESRD received 33 infrainguinal bypasses, while 65 limbs in 57 patients with functioning kidneys underwent 77 bypasses for limb salvage. The prevalence of diabetes is higher in the ESRD group (p = 0.03). RESULTS: perioperative mortality and patient survival rate in the follow-up period were significantly poorer in patients with ESRD (18% vs 0%; p = 0.001, and 45% vs 85%, p < 0.001, respectively). Most causes of death were related to atherosclerosis or respiratory diseases. In spite of no significant difference in 2-year primary and secondary graft patency rates and limb salvage between the ESRD and non-ESRD groups (76% vs 83%; p = 0.12, 85% vs 91%; p = 0.06, and 83% vs 93%; p = 0.06, respectively), two cases of early limb loss occurred as a result of uncontrolled infection in the ESRD group. In contrast to autogenous conduits, nonautogenous conduits revealed a poorer outcome in ESRD patients (p = 0.03). CONCLUSIONS: perioperative mortality and patient survival rate were significantly poorer in the ESRD group. Preoperative full evaluation of myocardial and brain ischaemia, revascularisation with autogenous conduits, appropriate treatment of wound infection, and strict follow-up for accompanying diseases may be needed in these patients. (+info)
The effects of Chinese medicines on micro-circulation of nail folds and blood flow velocity of limbs in the patients with arteriosclerotic obliteration.
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The effects of Chinese medicines on micro-circulation and blood flow velocity in arteries of the lower limbs were observed in 33 patients with arteriosclerotic obliteration (ASO). The results showed that the integral values of micro-circulation after treatment were obviously higher than those before treatment (P < 0.05 or P < 0.01). Blood flow velocity in arteries of the lower limbs determined with the color Doppler ultrasound detecting method after treatment were also obviously higher than those before treatment (P < 0.05 or P < 0.01). In this series of 33 ASO patients, the markedly effective rate was 36.36%, and the total effective rate was 63.64%. The observation indicates that the recipe prescribed according to the principle of supplementing qi and activating blood circulation can effectively improve micro-circulation in ASO patients, and accelerate blood flow in arteries of the lower limbs. (+info)
Serum concentrations of vascular endothelial growth factor and monocyte-colony stimulating factor in peripheral arterial disease.
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Vascular endothelial growth factor (VEGF) strongly promotes angiogenesis, and monocyte-colony stimulating factor (M-CSF) regulates the differentiation, proliferation, and survival of monocytes. Both VEGF and M-CSF are expressed in atherosclerotic lesions. The present study was performed to clarify the role of VEGF and M-CSF in the development of peripheral artery disease (PAD). The serum VEGF and M-CSF concentrations were determined in patients with arteriosclerosis obliterans (ASO) and thromboangitis obliterans (TAO). In both patient groups the serum VEGF concentrations were significantly higher than those in the control subjects. In contrast, the serum M-CSF concentrations in the ASO patients were significantly higher than those in both the TAO patients and control subjects, but there were no differences in the M-CSF concentrations between the TAO patients and control subjects. There was no correlation between the serum concentrations of VEGF and M-CSF. In conclusion, the serum VEGF concentration was increased in ASO and TAO patients, but increased concentration of M-CSF was seen only in ASO patients. These results may reflect a difference between ASO and TAO in disease pathogenesis. (+info)