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1.
Nurs Open ; 9(4): 2149-2158, 2022 07.
Article in English | MEDLINE | ID: mdl-35482535

ABSTRACT

AIMS: To explore and gain an understanding of patients' perceptions and experiences of their body and bodily function in connection with open surgery of abdominal aortic aneurysm. BACKGROUND: After the operation of an abdominal aortic aneurysm (AAA) it may be difficult for the patients to understand what the procedure means. DESIGN: The design was descriptive and based on an analysis of 13 audio-taped consultations with patients undergoing open surgery for AAA at a Swedish university hospital. The patients' age varied from 57-79 and the mean age was 71 (70.5 female). METHODS: A hermeneutic approach was used whereby patients were interviewed and draw a picture of their thoughts and experiences of the surgery and what had been done in their bodies. Once patients had finished their drawings, the interviewer asked what thoughts and experiences they had of the AAA. RESULTS: Patients described experiences as a process of "going from broken to whole again."


Subject(s)
Aortic Aneurysm, Abdominal , Endovascular Procedures , Aged , Aortic Aneurysm, Abdominal/surgery , Body Image , Endovascular Procedures/methods , Female , Humans
2.
BMJ Open ; 12(1): e049055, 2022 01 17.
Article in English | MEDLINE | ID: mdl-35039280

ABSTRACT

BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease but the high mortality rate is linked to high age and comorbidity pattern. Depression is associated with increased mortality in the general population and individuals with cardiovascular diseases, but this is sparsely studied for AAA. The aim was to examine the prognostic impact of depressive symptoms on all-cause mortality in individuals with AAA and compare with findings in a general population of the same age and risk profile. METHODS: Population-based prospective study including 36 616 participants (52.1% women) from the Trøndelag Health Study in Norway. A total of 9428 individuals died during a median follow-up of 10 years at ages 60-90 years. Depressive symptoms were defined by a Hospital Anxiety and Depression Scale-Depression score ≥8. Data on AAA diagnoses and death were obtained from medical records and national registers. HRs from Cox proportional hazard regression models are reported. RESULTS: A total of 4832 (13.2%) individuals reported depressive symptoms, whereas 583 (1.6%) AAAs were identified. The adjusted hazard of death was 2.66 times higher in persons with AAA compared with the general population (95% CI 2.39 to 2.97). Overall, there was no significant adverse effect of depressive symptoms in individuals with AAA (HR 1.15;95% CI 0.88 to 1.51), whereas an increased risk was seen in the general population (HR 1.23;95% CI 1.17 to 1.30). CONCLUSION: The overall risk of death was considerably higher in individuals with AAA compared with a general population of the same age and risk profile. Depressive symptoms did not significantly influence the risk of death in the AAA group.


Subject(s)
Aortic Aneurysm, Abdominal , Depression , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/epidemiology , Depression/epidemiology , Female , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Prospective Studies , Risk Factors
3.
BMJ ; 371: m3485, 2020 10 07.
Article in English | MEDLINE | ID: mdl-33028588

ABSTRACT

OBJECTIVE: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). DESIGN: Randomised controlled trial. SETTING: General population of older adults in Trondheim, Norway. PARTICIPANTS: 1567 of 6966 individuals born between 1936 and 1942. INTERVENTION: Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. MAIN OUTCOME MEASURE: All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. RESULTS: Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. CONCLUSION: This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.


Subject(s)
Aging , Exercise , Heart Rate/physiology , High-Intensity Interval Training/methods , Physical Functional Performance , Aged , Aging/physiology , Aging/psychology , Cause of Death , Exercise/physiology , Exercise/psychology , Female , Humans , Male , Mortality , Outcome Assessment, Health Care , Physical Fitness , Risk Reduction Behavior
4.
Circulation ; 142(17): 1633-1646, 2020 10 27.
Article in English | MEDLINE | ID: mdl-32981348

ABSTRACT

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. METHODS: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. RESULTS: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24-1.66]; P=1.6×10-6), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97-1.15]; P=0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratioPRS, 1.26 [95% CI, 1.18-1.36]; PPRS=2.7×10-11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratioPRS+family history+smoking, 1.24 [95% CI, 1.14-1.35]; PPRS=1.27×10-6). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. CONCLUSIONS: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.


Subject(s)
Aortic Aneurysm, Abdominal/genetics , Humans , Veterans
5.
SAGE Open Med ; 8: 2050312119900860, 2020.
Article in English | MEDLINE | ID: mdl-32002182

ABSTRACT

OBJECTIVE: This population-based retrospective cohort study investigates long-term results of femoral thrombendarterectomy combined with simultaneous endovascular intervention of the iliac or femoropopliteal vessels, or both, with focus on freedom from recurrent intervention, limb salvage and survival. METHODS: All patients undergoing femoral thrombendarterectomy and simultaneous endovascular intervention between 1999 and 2013 were included. Stratification was according to clinical symptoms, intermittent claudication or critical ischemia, with subgroups for rest pain and ulcer/gangrene, and for type of endovascular intervention, iliac, femoropopliteal or both. We assessed technical success, 30-day complications, freedom from recurrent intervention, survival and amputation free survival in all patients. Limb salvage was assessed in patients with critical ischemia. RESULTS: We identified 151 operations in 143 patients with a total of 164 limbs treated. A total of 13 patients had bilateral and 8 patients had subsequent contralateral operations. Indication was intermittent claudication in 87 (57.6%) and critical ischemia in 64 (42.4%) operations. Thirty-day mortality, only observed in critical ischemia, was 5/64 (7.8%). Freedom from recurrent intervention after 5 years was 91% in intermittent claudication and 70% in critical ischemia. In total, 84% of the patients with claudication were improved at the end of the study. Limb salvage at 5 years was 75% in critical ischemia, 93% in rest pain and 64% in patients with ulcer or gangrene. CONCLUSION: Femoral thrombendarterectomy combined with endovascular iliac or femoropopliteal intervention has good and durable results in intermittent claudication and critical ischemia, especially in patients with rest pain. In most cases, a single operation is sufficient.

6.
Scand Cardiovasc J ; 54(2): 130-137, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31909634

ABSTRACT

Objectives. The normal aortic diameter (AD) varies with gender, age and body surface area (BSA). The aortic size index (ASI) is defined as the AD divided by BSA. The primary aim of this study was to investigate if ASI is a predictor of development AAA, and to compare the predictive impact of ASI to that of the absolute AD. Design. Population-based prospective study including 4161 individuals (53.2% women) from the Tromsø study with two valid ultrasound measurements of the AD and no AAA at baseline (Tromsø 4, 1994). The primary outcome was AAA (AD ≥30 mm) in Tromsø 5 (2001). A secondary outcome was aortic growth of >5 mm over 7 years. Estimates of relative risk were calculated in logistic regression models. The main exposure variable was ASI. Adjustments were made for age, gender, smoking, body mass index, total and high-density lipoprotein (HDL) cholesterol, and hypertension. Results. In total, 124 incident AAAs (20% among women) were detected. In adjusted analyses, both ASI and AD were strong predictors of AAA, with similar results for men and women. Both ASI and AD were also significant predictors of aortic growth >5 mm. In comparison, AD was superior to ASI as a predictor of both endpoints. Conclusions. ASI was a significant predictor of both AAA development and aortic growth of >5 mm for both men and women, but not a better predictor of either outcomes compared to the AD. The role of ASI compared to the AD as a predictor of AAA development seems to be limited.


Subject(s)
Aorta/diagnostic imaging , Aortic Aneurysm, Abdominal/epidemiology , Ultrasonography , Adult , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnostic imaging , Female , Humans , Incidence , Male , Middle Aged , Norway/epidemiology , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , Sex Factors , Time Factors
7.
EJVES Vasc Forum ; 49: 23-29, 2020.
Article in English | MEDLINE | ID: mdl-33937897

ABSTRACT

OBJECTIVE: Current vascular grafts all have limitations. This study examined peritoneum as a potential graft material and the in vivo transfer of peritoneum into a functional artery like conduit after end to end anastomosis into the common carotid artery of sheep. The aim was to investigate whether implantation of a peritoneal tube into the arterial tree results in a structure with function, histological findings, and gene expression like an artery, and whether such arterialisation occurs through a conversion of the phenotype of peritoneal cells or from host cell migration into the implant. METHODS: Peritoneum with adherent rectus aponeurosis from sheep was used to form tubular vascular grafts that were implanted into the common carotid artery of six sheep, then removed after five months. Two sheep received allogenic peritoneal grafts and four sheep received autologous peritoneal grafts. RESULTS: One sheep died shortly after implantation, so five of the six sheep were followed. Five months after implantation, four of the five remaining grafts were patent. Three of four patent grafts were aneurysmal. The four patent grafts had developed an endothelial layer indistinguishable from that of the adjacent normal artery, and a medial layer with smooth muscle cells with a surrounding adventitia. The new conduit displayed vasomotor function not present at the time of implantation. DNA genotyping showed that the media in the new conduit consisted of recipient smooth muscle cells. Little difference in mRNA expression was demonstrated between the post-implantation conduit and normal artery. CONCLUSION: During a five month implantation period in the arterial system, peritoneum converted into a tissue that histologically and functionally resembled a normal artery, with a functional genetic expression that resembled that of an artery. Single nucleotide polymorphism analysis indicated that this conversion occurs through host cell migration into the graft.

8.
J Am Heart Assoc ; 8(21): e012535, 2019 11 05.
Article in English | MEDLINE | ID: mdl-31642357

ABSTRACT

Background Depression is associated with cardiovascular diseases, but the evidence is scarce regarding depression and risk of abdominal aortic aneurysms (AAA). The aim was to determine whether individuals with depressive symptoms have increased risk of AAA. Methods and Results This population-based prospective study included 59 136 participants (52.4% women) aged 50 to 106 years from the HUNT (Norwegian Nord-Trøndelag Health Study). Symptoms of depression were assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS). During a median follow-up of 13 years, there were 742 incident cases of AAA (201 women). A total of 6401 individuals (12.3%) reported depressive symptoms (defined as HADS depression scale [HADS-D]) ≥8) (52.5% women). The annual incidence rate of AAA was 1.0 per 1000 individuals. At all ages, the estimated proportion of individuals diagnosed with AAA was higher among those with depressive symptoms (log-rank test, P<0.001). People with HADS-D ≥8 were older than those with HADS-D<8 (median 57.8 versus 52.3 years, P<0.001) and a statistically significantly higher proportion of them (P<0.001) were smokers, overweight or obese, and reported a history of coronary heart disease, diabetes mellitus, and hypertension. In a Cox proportional hazard regression model adjusted for these factors, individuals with depressive symptoms had a ≈30% higher risk of AAA than those without (hazard ratio, 1.32, 95% CI 1.08-1.61, P=0.007). Conclusions This study shows that individuals with depressive symptoms have significantly higher risk of incident AAA, after adjustments for established risk factors.


Subject(s)
Aortic Aneurysm, Abdominal/epidemiology , Aortic Aneurysm, Abdominal/etiology , Depression/complications , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Norway , Prospective Studies , Risk Assessment
9.
SAGE Open Med ; 7: 2050312119853434, 2019.
Article in English | MEDLINE | ID: mdl-31205704

ABSTRACT

OBJECTIVES: The primary aim of this study was to investigate the rate of sac enlargement and secondary procedures after 5 years when instructions for use are strictly applied with endovascular aortic repair. The secondary aim was to investigate if strict indications with endovascular aortic repair, rendering more open operations, would change the general outcome of patients with abdominal aortic aneurysm. MATERIALS AND METHODS: Patients having their abdominal aortic aneurysm procedure in a single institution between 01 January 2002 and 31 December 2006 were included. Indications for endovascular aortic repair were as follows: aortic neck: length 15 mm or more, diameter 32 mm or less and straight configuration; iliac arteries: length > 10 mm, 7.5-20 mm in diameter. Sac enlargement was defined as an increase in diameter of 5 mm or more. RESULTS: A total of 123 patients were intended to be treated electively with endovascular aortic repair from 2002 to 2007 using Cook Zenith stent grafts. In the same period, 147 patients were treated with elective open repair. At 5 years, 7.3% (N = 9) of the elective intended-to-treat patients with endovascular aortic repair had a sac enlargement. Thirty-five percent of the patients were registered with endoleaks, 13% of the patients had secondary procedures, 12.2% of the patients had early and 6.5% late complications during the follow-up period. Aneurysm rupture was seen in 1.6% of the patients. During the 5-year follow-up period, 34 (27.6%) of the endovascular aortic repair patients died. Five-year mortality for open repair was 23.8%, and 12.2% of the open repair patients had secondary procedures. CONCLUSION: Endovascular aortic repair for abdominal aortic aneurysm in accordance with instructions for use gives a low long-term risk for increased diameter and low rate of secondary procedures. There was similar mortality after elective endovascular aortic repair and open repair for abdominal aortic aneurysm. Applying endovascular aortic repair according to instructions for use does not seem to change the general outcome of patients with abdominal aortic aneurysm but improves the outcome with the method.

10.
J Vasc Surg ; 70(5): 1436-1445.e2, 2019 11.
Article in English | MEDLINE | ID: mdl-31248762

ABSTRACT

OBJECTIVE: The delayed development of abdominal aortic aneurysm (AAA) in women compared with men might be secondary to a protective effect from endogenous estrogens. The role of postmenopausal hormone therapy remains unclear. The aim of the present study was to evaluate the effect of female sex hormones compared with other risk factors associated with AAA through a long-term study of a large female cohort. METHODS: The present prospective cohort study included 20,024 postmenopausal women from the Norwegian Nord-Trøndelag Health Study. A total of 201 cases of AAA were identified during a median follow-up period of 18 years (295,554 person-years; 1995-2014). The data were recorded from questionnaires, physical measurements, medical records, blood sample test results, and the Norwegian Cause of Death Registry. The effect of risk factors was evaluated in a multiple Cox regression analysis. Multiple imputation was performed for missing data (n = 50 data sets). The serum estradiol concentrations in women with and without incidental AAAs were compared. The median interval from blood sample collection to the AAA diagnosis was 7 years. RESULTS: Current smokers had >10-fold increased risk of incident AAA during the follow-up period (hazard ratio [HR], 10.9; 95% confidence interval [CI], 7.4-16.1). Positive associations were found for hypertension (HR, 2.0; 95% CI, 1.4-3.0) and coronary heart disease (HR, 2.2; 95% CI, 1.6-3.2). The HR associated with the current use of postmenopausal hormone therapy was 0.58 (95% CI, 0.6-1.5). No substantial difference in estradiol concentrations was found between women with and without AAA (P = .075). CONCLUSIONS: The effect of female sex hormones on the risk of incident AAAs in women, as evaluated by the serum concentrations of estradiol and the use of postmenopausal hormone therapy, is clinically less important than the strong associations found with smoking, hypertension, and coronary heart disease.


Subject(s)
Aortic Aneurysm, Abdominal/epidemiology , Coronary Disease/epidemiology , Estradiol/blood , Hypertension/epidemiology , Smoking/epidemiology , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/etiology , Coronary Disease/blood , Coronary Disease/complications , Female , Follow-Up Studies , Hormone Replacement Therapy/adverse effects , Humans , Hypertension/blood , Hypertension/complications , Incidence , Longitudinal Studies , Middle Aged , Norway/epidemiology , Postmenopause/blood , Postmenopause/drug effects , Proportional Hazards Models , Prospective Studies , Risk Assessment , Risk Factors , Smoking/adverse effects , Smoking/blood , Time Factors
11.
Vasc Endovascular Surg ; 53(2): 112-117, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30803415

ABSTRACT

OBJECTIVE:: This population-based retrospective cohort study investigates long-term results of femoropopliteal bypass and femoropopliteal endovascular intervention (PTA) in patients with critical ischemia, with focus on limb salvage and amputation-free survival. METHODS:: All patients who underwent femoropopliteal bypass or femoropopliteal PTA for critical ischemia without other simultaneous intervention between 1999 and 2013 were included. Stratification was according to treatment modality and symptoms, rest pain, or ischemic ulcer/gangrene. We assessed technical success, 30-day complications, length of stay, recurrent interventions, limb salvage, survival, and amputation-free survival in all patients. RESULTS:: We identified 292 operations in 264 patients, 140 bypass and 152 PTA. In 32 PTA cases, the patients were explicitly deemed unfit for bypass surgery. This group had significantly inferior technical success and limb salvage ( P = .00). In other patients, technical success was 96% for bypass and 93% for PTA, while limb salvage after 5 years was 78% for bypass and 81% for PTA. Reoperation for local complications was performed in 16% after bypass and 2% after PTA ( P = .00). Mean length of stay was 8 days after bypass and 1.9 days after PTA ( P = .00). CONCLUSIONS:: Long-term follow-up showed similar technical success and good limb salvage for both PTA and bypass patients in this clinical cohort. Patients who were unfit for bypass surgery had significantly inferior technical success and limb salvage. PTA was associated with shorter hospital stay and fewer reoperations for local complications. The findings support a PTA first strategy in all cases where technical success is likely.


Subject(s)
Amputation, Surgical , Angioplasty, Balloon/methods , Femoral Artery/surgery , Ischemia/surgery , Limb Salvage/methods , Peripheral Arterial Disease/surgery , Popliteal Artery/surgery , Postoperative Complications/surgery , Vascular Grafting/methods , Aged , Aged, 80 and over , Amputation, Surgical/adverse effects , Amputation, Surgical/mortality , Angioplasty, Balloon/adverse effects , Angioplasty, Balloon/mortality , Critical Illness , Female , Femoral Artery/diagnostic imaging , Femoral Artery/physiopathology , Humans , Ischemia/diagnostic imaging , Ischemia/mortality , Ischemia/physiopathology , Length of Stay , Limb Salvage/adverse effects , Limb Salvage/mortality , Male , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/mortality , Peripheral Arterial Disease/physiopathology , Popliteal Artery/diagnostic imaging , Popliteal Artery/physiopathology , Postoperative Complications/diagnostic imaging , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Progression-Free Survival , Registries , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vascular Grafting/adverse effects , Vascular Grafting/mortality
12.
J Transl Med ; 15(1): 130, 2017 06 07.
Article in English | MEDLINE | ID: mdl-28592294

ABSTRACT

BACKGROUND: Exercise of patients with intermittent claudication improves walking performance. Exercise does not usually increase blood flow, but seems to increase muscle mitochondrial enzyme activities. Although exercise is beneficial in most patients, it might be harmful in some. The mitochondrial response to exercise might therefore differ between patients. Our hypothesis was that changes in walking performance relate to changes in mitochondrial function after 8 weeks of exercise. At a subgroup level, negative responders decrease and positive responders increase mitochondrial capacity. METHODS: Two types of exercise were studied, calf raising and walking (n = 28). We wanted to see whether there were negative and positive responders, independent of type of exercise. Measurements of walking performance, peripheral hemodynamics, mitochondrial respiration and content (citrate synthase activity) were obtained on each patient before and after the intervention period. Multiple linear regression was used to test whether changes in peak walking time relate to mitochondrial function. Subgroups of negative (n = 8) and positive responders (n = 8) were defined as those that either decreased or increased peak walking time following exercise. Paired t test and analysis of covariance was used to test changes within and between subgroups. RESULTS: Changes in peak walking time were related to changes in mitochondrial respiration supported by electron transferring flavoprotein (ETF + CI)P (p = 0.004), complex I (CI + ETF)P (p = 0.003), complex I + complex II (CI + CII + ETF)P (p = 0.037) and OXPHOS coupling efficiency (p = 0.046) in the whole group. Negative responders had more advanced peripheral arterial disease. Mitochondrial respiration supported by electron transferring flavoprotein (ETF + CI)P (p = 0.0013), complex I (CI + ETF)P (p = 0.0005), complex I + complex II (CI + CII + ETF)P (p = 0.011) and electron transfer system capacity (CI + CII + ETF)E (p = 0.021) and OXPHOS coupling efficiency decreased in negative responders (p = 0.0007) after exercise. Positive responders increased citrate synthase activity (p = 0.010). CONCLUSIONS: Changes in walking performance seem to relate to changes in mitochondrial function after exercise. Negative responders have more advanced peripheral arterial disease and decrease, while positive responders increase mitochondrial capacity. Trial registration ClinicalTrials.gov ID: NCT023110256.


Subject(s)
Exercise/physiology , Intermittent Claudication/physiopathology , Mitochondria/metabolism , Walking/physiology , Aged , Cell Respiration , Female , Hemodynamics , Humans , Male , Time Factors
13.
J Vasc Surg ; 65(5): 1473-1482, 2017 05.
Article in English | MEDLINE | ID: mdl-28285932

ABSTRACT

BACKGROUND: Symptoms of intermittent claudication (IC) are improved by exercise. The improvement might be secondary to increased blood perfusion or increased muscle mitochondrial capacity. Ischemia followed by reperfusion, also named preconditioning, is known to stimulate the mitochondria. We focused on a calf raise exercise inducing preconditioning in the calf muscle of patients with IC. We hypothesized that 8 weeks of this exercise would increase walking performance and mitochondrial capacity without a change in blood flow. METHODS: Patients with IC were randomized to either a calf raise exercise group (n = 14) or a traditional walking exercise group (n = 15). The calf raise group was instructed to perform a specific type of calf raise exercise three times a day. The walking group was instructed to walk near the pain threshold at least 30 minutes three times a week. Both interventions lasted 8 weeks and were not supervised. Measurements of walking performance, mitochondrial capacity, peak oxygen uptake, peripheral hemodynamics, and health-related quality of life were obtained on each patient before and after the intervention period. Adherence was measured by a training diary, and an activity monitor was used. RESULTS: The calf raise group improved pain-free walking distance by 44 meters (P = .04) and maximal walking distance by 99 meters (P = .047). Furthermore, claudication onset time increased by 123 seconds (P = .02), and peak walking time increased by 104 seconds (P = .01). The calf raise group increased the enzyme citrate synthase activity, which is a biomarker of mitochondrial volume-density in the muscle tissue (P = .02). The walking group did not increase any of these variables. Maximal blood flow, peak oxygen uptake, and mitochondrial respiration did not change in any group. The calf raise group experienced less disease anxiety (P < .01). Adherence to the instruction of exercise was 100% in the calf raise group and 80% in the walking group. The calf raise group maintained physical activity. A reduction in activity (P < .01) was found in the walking group. CONCLUSIONS: Calf raise exercise improves walking performance and increases mitochondrial volume-density in the gastrocnemius muscle without increasing blood flow in patients with IC.


Subject(s)
Exercise Therapy/methods , Exercise Tolerance , Intermittent Claudication/therapy , Muscle, Skeletal/blood supply , Walking , Actigraphy , Aged , Aged, 80 and over , Exercise Test , Female , Health Status , Humans , Intermittent Claudication/diagnosis , Intermittent Claudication/physiopathology , Lower Extremity , Male , Middle Aged , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Norway , Oxygen Consumption , Pain Measurement , Prospective Studies , Quality of Life , Recovery of Function , Time Factors , Treatment Outcome
14.
PLoS One ; 11(10): e0165038, 2016.
Article in English | MEDLINE | ID: mdl-27760222

ABSTRACT

PURPOSE: Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease. METHODS: One group of patients with peripheral vascular disease (n = 11) and one group of healthy older adults (n = 11) were included. Patients performed one session of continuous calf raises followed by 5 extra repetitions after initiation of pain. Healthy older adults performed 100 continuous calf raises. Gastrocnemius muscle biopsies were collected at baseline and 15 minutes, one hour, three hours and 24 hours after one session of calf raise exercise. A multi substrate (octanoylcarnitine, malate, adp, glutamate, succinate, FCCP, rotenone) approach was used to analyze mitochondrial respiration in permeabilized fibers. Mixed-linear model for repeated measures was used for statistical analyses. RESULTS: Patients with peripheral vascular disease have a lower baseline respiration supported by complex I and they increase respiration supported by complex II at one hour post-exercise. Healthy older adults increase respiration supported by electron transfer flavoprotein and complex I at one hour and 24 hours post-exercise. CONCLUSION: Our results indicate a shift towards mitochondrial respiration supported by complex II as being a pathophysiological component of peripheral vascular disease. Furthermore exercise stimulates mitochondrial respiration already after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT01842412.


Subject(s)
Electron Transport Complex II/metabolism , Exercise Test/methods , Mitochondria, Muscle/physiology , Peripheral Vascular Diseases/physiopathology , Aged , Cell Respiration , Electron Transport Complex I/metabolism , Female , Humans , Male , Middle Aged , Muscle, Skeletal/metabolism , Oxygen Consumption , Peripheral Vascular Diseases/metabolism
15.
Eur Clin Respir J ; 3: 30010, 2016.
Article in English | MEDLINE | ID: mdl-27608269

ABSTRACT

BACKGROUND: Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment. METHODS: To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting - a 'proof-of-principle' study. RESULTS: The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal. CONCLUSIONS: The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use.

16.
J Vasc Res ; 48(4): 307-15, 2011.
Article in English | MEDLINE | ID: mdl-21273785

ABSTRACT

BACKGROUND/AIMS: Formation of intimal hyperplasia following angioplastic procedures can lead to complications, including restenosis and accelerated atherosclerosis. The vessel wall media is a main source of neointimal cells. However, evidence suggests that there are additional cell sources, such as the adventitia. Here we investigate whether an extensive loss of vascular smooth muscle cells (VSMCs) in the media results in less intimal hyperplasia or if there is compensatory cell recruitment from the adventitia. METHODS: A balloon catheter was pulled through the rabbit carotid artery 4 times (major injury) or 2 times (minor injury). Adventitial cells were labeled with 5-bromo-2-deoxyuridine or PKH26. RESULTS: The major injury, but not the minor injury, resulted in a complete loss of VSMCs in large parts of the media and significant leukocyte infiltration. The major injury resulted in less neointima compared with the minor injury. The thinnest neointima was seen at the most injured parts of the media in the major injury group. Cell-tracking experiments showed that the media, but not the adventitia, served as a source of neointimal cells. CONCLUSION: An augmented angioplastic injury with extensive VSMC loss in rabbits reduced the degree of intimal hyperplasia. No compensatory recruitment of neointimal cells from the adventitia occurred.


Subject(s)
Angioplasty, Balloon/adverse effects , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , Tunica Intima/pathology , Animals , Bromodeoxyuridine/metabolism , Cell Movement , Connective Tissue/pathology , Hyperplasia , Leukocytes/physiology , Male , Neointima , Rabbits
17.
J Vasc Surg ; 50(3): 492-9, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19700089

ABSTRACT

OBJECTIVES: Surgical intervention in the treatment of abdominal aortic aneurysms (AAA) can affect sexual functions, resulting in a negative impact on the quality of life. The aim of this study was to investigate the preoperative information given about sexual functions and to compare the functional changes after open (OR) and endovascular repair (EVAR) for patients with AAA during one year after treatment. METHODS: Seventy-six patients participated in the study (40 OR and 36 EVAR). A questionnaire was used to measure the sexual function preoperatively, and then after one month and one year following surgical interventions. Four aspects related to sexual function were studied: interest in sex, quality of erection, ability to achieve orgasm, and ejaculation. Two questions about the preoperative information covering the sexual function and another two questions about the patients concern for their sexual activities were also added. Fisher's exact test was used to test for significant relative changes within each group of treatment for the variables studied. RESULTS: Ninety-one percent reported that they did not receive any preoperative information about the risk for any possible negative impact on the sexual function. None of the EVAR patients were given such information. Forty-two percent of all patients felt some anxiety about having sex before the operation, which decreased to 7% after one year. About 22% reported having strong/moderate ability of their erection and 54% reported this as being weak/very weak preoperatively. Patients who preoperatively had reported some form of sexual interest had experienced a significant impairment in sex (P < .039) one year after the interventions. Patients treated with EVAR reported a significant impairment in the quality of erection (P < .033) and their ability to achieve ejaculation (P < .047) one year after the operation. A similar tendency was seen in the OR group, but did not achieve statistical significance. CONCLUSION: Few patients were given or understood any preoperative information concerning the risk and possibility of a negative impact on their sexual function following surgical interventions. This was especially reported by patients in the EVAR group. Following the operation, the reported sexual interest and ability was decreased among patients in both groups. When only those patients who had reported some form of interest in sexual activity before the intervention were analyzed, a small significant impairment in quality of erection and achieving ejaculation could be found during the one year follow-up in the EVAR group.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Sexual Behavior , Sexual Dysfunction, Physiological/etiology , Sexual Dysfunctions, Psychological/etiology , Aged , Aged, 80 and over , Comprehension , Ejaculation , Elective Surgical Procedures , Female , Follow-Up Studies , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Patient Education as Topic , Penile Erection , Prospective Studies , Risk Assessment , Sexual Dysfunction, Physiological/physiopathology , Sexual Dysfunctions, Psychological/physiopathology , Surveys and Questionnaires , Time Factors , Treatment Outcome
18.
Circ Res ; 103(1): 61-9, 2008 Jul 03.
Article in English | MEDLINE | ID: mdl-18511849

ABSTRACT

Lipoma preferred partner (LPP) was recently recognized as a smooth muscle marker that plays a role in smooth muscle cell migration. In this report, we focus on the transcriptional regulation of the LPP gene. In particular, we investigate whether LPP is directly regulated by serum response factor (SRF). We show that the LPP gene contains 3 evolutionarily conserved CArG boxes and that 1 of these is part of an alternative promoter in intron 2. Quantitative RT-PCR shows that this alternative promoter directs transcription specifically to smooth muscle containing tissues in vivo. By using chromatin immunoprecipitation, we demonstrate that 2 of the CArG boxes, including the promoter-associated CArG box, bind to endogenous SRF in cultured aortic smooth muscle cells. Electrophoretic mobility-shift assays show that the conserved CArG boxes bind SRF in vitro. In reporter experiments, we show that the alternative promoter has transcriptional capacity that is dependent on SRF/myocardin and that the promoter associated CArG box is required for that activity. Finally, we show by quantitative RT-PCR that the alternative promoter is strongly downregulated in SRF-deficient embryonic stem cells and in smooth muscle tissues derived from conditional SRF knockout mice. Collectively, our data demonstrate that expression of LPP in smooth muscle is mediated by an alternative promoter that is regulated by SRF/myocardin.


Subject(s)
Aorta/metabolism , Cytoskeletal Proteins/biosynthesis , Introns/physiology , Myocytes, Smooth Muscle/metabolism , Nuclear Proteins/metabolism , Serum Response Element/physiology , Serum Response Factor/metabolism , Trans-Activators/metabolism , Animals , Aorta/cytology , Cell Movement/physiology , Cells, Cultured , Cytoskeletal Proteins/genetics , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , LIM Domain Proteins , Male , Mice , Myocytes, Smooth Muscle/cytology , Nuclear Proteins/genetics , Serum Response Factor/genetics , Trans-Activators/genetics , Transcription, Genetic/physiology
19.
Cardiovasc Res ; 67(2): 326-32, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-15885671

ABSTRACT

OBJECTIVE: Accumulation of intimal smooth muscle cells (SMC) is an important event in vein graft-stenosis. Different SMC sources have been reported, but their interrelations have been poorly studied. In a mouse vein graft model we investigated whether recipient-derived intimal SMCs are recruited from the surrounding tissue and whether blockage of SMC recruitment from the surrounding tissue and/or the donor vein will reduce neointimal formation. METHODS: To detect recipient-derived cells, wild-type veins were implanted into ROSA26 transgenic mice. To block cell recruitment from the surrounding tissue, implanted veins were isolated with a tube-shaped plastic film. To exclude vein-derived cells in the neointimal formation, acellular veins were implanted. RESULTS: In vein grafts isolated from the surrounding tissue the recipient contribution became minimal, but the total number of SMCs was not decreased. Acellular grafts contained an equal number of intimal SMCs as cellular controls after 4 weeks. Isolation of acellular grafts from the surrounding tissue decreased the number of intimal SMCs by 90%. CONCLUSIONS: Recipient-derived SMCs are mainly recruited from the surrounding tissue. Cell recruitment from either the vein or the surrounding tissue is enough to form a neointima. Therefore, a simultaneous inhibition of both these sources is needed to reduce accumulation of intimal SMCs.


Subject(s)
Arteriosclerosis/prevention & control , Graft Occlusion, Vascular/prevention & control , Muscle, Smooth, Vascular/pathology , Tunica Intima/pathology , Veins/transplantation , Actins/analysis , Animals , Arteriosclerosis/pathology , Biomarkers/analysis , Cell Count , Cell Movement , Graft Occlusion, Vascular/pathology , Hyperplasia , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myocytes, Smooth Muscle/pathology , Stents
20.
J Vasc Res ; 42(1): 13-20, 2005.
Article in English | MEDLINE | ID: mdl-15608438

ABSTRACT

Altered flow conditions are presumed to cause stenosis in vein grafts due to exaggerated neointimal formation. The aim of this study was to establish a mouse model of flow-regulated intimal hyperplasia (IH) in vein grafts. The caval vein was grafted into the common carotid artery of 38 mice, followed by modulation of the blood flow, resulting in vein grafts with high (HF) and low flow (LF). The vessel wall thickening was evaluated after 3, 14 and 42 days by morphometric analyses and immunohistochemistry. There was an immediate significant change in flow, which was persistent throughout the time of observation. After 42 days, flow was increased 2.7 times in HF animals compared to LF animals. The vessel wall was composed of two layers where the inner layer was positive for alpha-actin and considered as IH. The area of neointimal formation was 74% larger in the LF group compared to the HF group. The present study demonstrates that flow regulates IH in vein grafts in mice. This model gives the potential to study the effect of shear stress on vascular biology in genetically modified animals.


Subject(s)
Tunica Intima/pathology , Veins/transplantation , Animals , Cell Count , Cell Division , Hyperplasia , Male , Mice , Mice, Inbred C57BL , Muscle, Smooth, Vascular/pathology , Regional Blood Flow , Shear Strength , Veins/pathology , Veins/physiology
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