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Eric Wahlberg

Publications and source records attributed to Eric Wahlberg.

12 recordsLinked to original sources
PubMed2004

Vascular endothelial cell growth factor and fibroblast growth factor 2 expression in patients with critical limb ischemia.

BACKGROUND: For patients with critical limb ischemia (CLI), there is a great need for alternative treatment strategies. One option is therapeutic angiogenesis by administration of vascular growth factors. The lack of convincing clinical data supporting this strategy may be due to the ignorance of endogenous angiogenic processes in CLI. To evaluate the importance of vascular growth factors in the pathogenesis in CLI and provide information for clinical growth factor treatment trials, we determined the levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in the ischemic legs of patients with this disease. METHODS: Skin and muscle biopsies from the calf and groin were gathered from 25 patients with CLI. Control samples came from 10 orthopedic patients and from 5 patients who were undergoing coronary artery bypass. The concentration of VEGF and FGF-2 in the biopsies was measured by enzyme-linked immunoassay, and to localize growth factor production, biopsied sections were immunostained. RESULTS: Patients with CLI had lower levels of VEGF in distal skin samples than in proximal ones (mean difference: 16.7 pg/mg total protein, 95% confidence interval: -1.0 to -32.3, P =.038), but these levels were similar to those in distal samples from control subjects (8.0, -4.6 to 20.5, P =.65). In muscle, VEGF concentrations were similar in calf and groin (5.4, -12.4 to 23.1, P =.55), but distal levels were higher than in distal samples from control subjects (23.7, 1.2 to 56.7, P =.028). Skin FGF levels tended to be higher in distal samples (45.3, 26.5 to 117.5, P =.090) and were higher than in skin from control subjects (106.2, -11.4 to 223.8, P =.050). Also in muscle, distal samples had higher levels of FGF-2 (35.6, -1.6 to 59.7, P =.006), but these levels were similar to what was found in control subjects (29.4., -16.3 to 81.2, P =.39). Growth factors were located in connective tissue between muscle fibers. In skin, the predominant FGF-2 staining was just below the epidermal layer, whereas VEGF appeared in the dermal layer. CONCLUSIONS: The results indicate that there are elevated concentrations of FGF-2 in calf muscle, whereas VEGF concentrations do not appear to be higher in the ischemic part of the leg in patients with CLI. These findings suggest that VEGF supplementation may be a more appropriate strategy for therapeutic angiogenesis to the calf area for CLI than FGF-2.

Aged↗
PubMed2003

Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2.

The establishment of functional and stable vascular networks is essential for angiogenic therapy. Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable for more than a year even after depletion of angiogenic factors. In both rat and rabbit ischemic hind limb models, PDGF-BB and FGF-2 together markedly stimulated collateral arteriogenesis after ligation of the femoral artery, with a significant increase in vascularization and improvement in paw blood flow. A possible mechanism of angiogenic synergism between PDGF-BB and FGF-2 involves upregulation of the expression of PDGF receptor (PDGFR)-alpha and PDGFR-beta by FGF-2 in newly formed blood vessels. Our data show that a specific combination of angiogenic factors establishes functional and stable vascular networks, and provides guidance for the ongoing clinical trials of angiogenic factors for the treatment of ischemic diseases.

Animals↗
PubMed2003

Arteriogenesis in peripheral arterial disease.

Lower extremity peripheral arterial disease (PAD) most frequently presents with lower limb pain on walking--intermittent claudication. As the disease progresses the patient might suffer from rest pain and/or ischemic ulceration--critical limb ischemia (CLI). The management of patients with PAD consists of life-style modifications and pharmacotherapy addressing the risk factors to minimize the risk for disease progression and mortality in myocardial infarction and stroke. Symptomatic invasive treatment consists of surgical or endovascular revascularization. Unfortunately, about 20-30% of patients with CLI can not be treated by any of these methods and the only option for them is often amputation. For this group of patients there is a great need for alternative treatment strategies and several strategies are currently tested to stimulate collateral artery growth (arteriogenesis). Arteriogenesis is defined as growth of preexisting arteriolar connections into true collateral arteries. It relies on a complex combination of increased shear stress, different growth factors, cytokines, proteolytic enzymes and initial local inflammation. It is probable that this process is important for disease progression and the pathophysiology of leg ischemia, but its impact needs to be further elucidated. Such efforts will also benefit attempts to stimulate arteriogenesis as therapy for leg ischemia. This article briefly discusses the basic mechanisms underlying arteriogenesis, and speculates how this knowledge influences our view of the pathophysiology and treatment of PAD, particularly lower limb ischemia.

Animals↗
PubMed2002

Vascular growth factor expression in a rat model of severe limb ischemia.

BACKGROUND: In ischemic tissue hypoxia induces production of vascular growth factors, especially VEGF, which initiate local angiogenesis. Collateralization-or arteriogenesis-occurs at a distance from the ischemic tissue and depends on different growth factors such as FGF-2. A spatial discrepancy in endogenous growth factor production in limb ischemia may have implications for therapeutic angiogenesis. The present study elucidates if such spatial and temporal variation occurs. MATERIALS AND METHODS: A two-staged procedure was performed to generate severe long-lasting limb ischemia in 60 rats. At 1, 7, 28, and 56 days, subgroups were subjected to perfusion assessment with laser Doppler imaging and angiography. Muscle samples and foot skin were gathered to measure growth factor expression and signs of angiogenesis using immunohistochemistry. RESULTS: There was an early twofold increase (P < 0.05) in both VEGF and FGF-2 levels in distal muscle from the ischemic leg, but no significant rise in the thigh. The concentrations decreased over time with an exception for VEGF in soleus and FGF-2 in anterior tibial muscle, which remained high. An increased capillarity was noted (P < 0.05) in soleus after 28 days, and the number of BrdU-positive ECs was elevated in all ischemic samples at 56 days. Collateral arteries were observed on the angiograms after 7 days. CONCLUSIONS: The results suggest that in limb ischemia any major increase in vascular growth factor production is limited to ischemic tissue. The spatial and temporal distribution patterns of growth factor production are complex and to a great extent influenced by inflammation.

Angiography↗
PubMed2002

Sex-related differences in outcome after vascular interventions for lower limb ischemia.

OBJECTIVE: The purpose of this study was to investigate sex-related differences in outcome, defined as amputation rate and survival in patients treated for lower limb ischemia. MATERIAL AND METHOD: Age, sex, and type of procedure for all patients undergoing vascular interventions for lower limb ischemia in Stockholm, Sweden, from 1970 to 1994, were obtained from the National Board of Health and Welfare. All patients who underwent amputation after treatment were analyzed separately. Data on deceased patients were extracted from the cause-of-death register. RESULTS: Women had lower survival rates than men at 30 days and 1 and 5 years after operation (89% vs 92%, 75% vs 80%, and 50% vs 55%; P <.001). In the multivariate analysis of risk factors for death during the whole study period, increasing age, calendar year (1980 to 1989), and male sex were significant risk factors (P <.001). The percentage of women who underwent amputation after treatment was comparable with the percentage of men who underwent amputation (11.4% vs 10.2%, P =.075). The multivariate analysis identified increased age and calendar year (1985 to 1994) as important risk factors for amputation (P <.001). Female sex was not found to increase the risk for amputation. Patients who underwent amputation were older than patients with intact limbs (73 vs 68 years, P <.001). The highest percentage of patients who underwent amputation was found among those treated with femorodistal bypass (20%, P =.001). CONCLUSIONS: Female sex is not an important risk factor for poor outcome after treatment for lower limb ischemia, when their increased age has been accounted for. These results imply that we should continue to consider age and type of procedure when estimating outcome, and women should not be refused an intervention on a sex-related basis. We should possibly be more selective toward men considering their higher mortality rates.

Adolescent↗
PubMed2002

Aortic clamping during elective operations for infrarenal disease: The influence of clamping time on renal function.

OBJECTIVE: Aortic clamping proximal to the renal arteries is sometimes necessitated during infrarenal and juxtarenal aortic surgery and may be associated with an increased risk of renal ischemia and its consequences. The aim of the study was to estimate this risk and possibly identify a "safe" duration of renal ischemia. METHODS: Medical records were retrospectively reviewed for 60 consecutive patients (from 1987 to 1994) with abdominal aortic aneurysm (n = 43) and occlusive disease (n = 17) confined to the infrarenal or juxtarenal aorta who underwent infrarenal aortic reconstruction with temporary suprarenal clamping. The data obtained included risk factors, preoperative and postoperative serum creatinine level, blood urea nitrogen (BUN) value, proteinuria before surgery, and suprarenal clamping times. RESULTS: The mean age of the patients was 64.4 years (+/- 11.4 years), and 74% were men. Concomitant cardiac disease was present in 41% of the patients, and 9% had diabetes. The preoperative creatinine level was 1.21 mg/dL (+/- 0.54 mg/dL), and the BUN value was 16.6 mg/dL (+/- 7.8 mg/dL). During surgery, blood flow to the renal arteries was interrupted for 32.0 minutes (+/- 17 minutes). None of the surviving patients needed dialysis or had signs of acute renal failure after the operations, but transient azotemia (rise in creatinine level) occurred in 23% of the patients. Risk factors for this condition were high preoperative creatinine values and hypotension during surgery, but the main determinant was total renal ischemia time. Odds ratios for such transient renal dysfunction showed as much as a 10-fold risk when suprarenal aortic clamping was greater than 50 minutes as compared with 30 minutes or less. CONCLUSION: Postoperative renal function impairment is rare in this group of patients. If suprarenal clamp duration (renal ischemia time) is brief, patients with normal preoperative creatinine levels exhibit no increase or a marginal increase in BUN or creatinine levels after surgery. Accordingly, suprarenal aortic clamping less than 50 minutes in this patient group appears safe and well tolerated.

Adult↗
PubMedDate not supplied

Reproductive history in women with lower limb ischemia.

The purpose of this study was to identify reproductive factors that may contribute to the development of arteriosclerosis in the leg arteries by comparing the reproductive history of women with lower limb ischemia to a reference group of women. All 173 female patients treated for chronic lower limb ischemia with surgical or endovascular procedures performed from 1994 to 1996 at a university clinic received a validated questionnaire to which 116 (67%) responded. The reference group, 348 women, 197 (57%) of whom responded, was recruited randomly from the hospital catchment area. The 2 groups were similar regarding age at menopause and menarche, pregnancies, salpingo-oophorectomies, and hormone replacement therapy. There was a higher number of women who had used oral contraceptives in the reference group than in the patient group (53% vs 16%, p < 0.001). The same results were found when comparing the subgroup of patients younger than 55 years to the references. No association between reproductive history and development of lower limb ischemia could be found. Our results support that use of oral contraceptives early in life is not associated with an increased risk for lower limb ischemia.

Adult↗
PubMedDate not supplied

Risk factors for poor collateral development in claudication.

The objective of this retrospective, cross-sectional study was to determine risk factors for poor collateral development in patients with claudication. The authors listed all patients with calf claudication who had undergone angiography in this hospital between 1999 and 2001 and extracted those with superficial femoral artery (SFA) occlusion, a popliteal artery without major lesions, and at least 1 patent calf artery. Forty-five patients met the criteria, and concomitant disease and claudication characteristics, ankle/brachial index (ABI) and number of outflow vessels were recorded. Three blinded observers calculated the number of collaterals on the angiograms, and the collateral count was related to the other factors by use of regression analysis. The mean patient age was 69 years (SD 11), and 62% were women. Their walking distance was 90 m (77) and ABI 0.47 (0.15). Thirty-three percent had diabetes and 50% had duration of symptoms longer than 5 years. The mean number of collaterals bypassing the occlusion was 15.1 (SD 4.8). Univariate regression analysis indicated an association (p <0.08) between few collateral vessels and diabetes, short duration of symptoms, current smoking habits, and old age. In the multivariate analysis only diabetes and short duration of symptoms were related to having few collaterals. In patients with claudication and SFA occlusion, few collaterals from the deep femoral artery appear to be associated with having diabetes and a short duration of symptoms.

Age Factors↗