Martin Bahls

Impact of porcine maternal aerobic exercise training during pregnancy on endothelial cell function of offspring at birth.

The purpose of this investigation was to test the hypothesis that maternal exercise training during pregnancy enhances endothelial function in offspring at birth. Six-month-old gilts (n = 8) were artificially inseminated and randomized into exercise-trained (n = 4) and sedentary groups (n = 4). Exercise training consisted of 15 weeks of treadmill exercise. The thoracic aorta of offspring were harvested within 48 h after birth and vascular responsiveness to cumulative doses of endothelium-dependent (bradykinin: 10-11-10-6 M) and independent (sodium nitroprusside: 10-10-10-4 M) vasodilators were assessed using in vitro wire myography. Female offspring from the exercised-trained gilts had a significantly greater endothelium-dependent relaxation response in the thoracic aorta when compared with the male offspring and female offspring from the sedentary gilts. The results of this investigation demonstrate for the first time that maternal exercise during pregnancy produces an enhanced endothelium-dependent vasorelaxation response in the thoracic aortas of female offspring at birth.

Effect of High‐Calcium Diet on Coronary Artery Disease in Ossabaw Miniature Swine With Metabolic Syndrome

Background Calcium is a shortfall essential nutrient that has been a mainstay of osteoporosis management. Recent and limited findings have prompted concern about the contribution of calcium supplementation to cardiovascular risk. A proposed mechanism is through the acceleration of coronary artery calcification. Determining causality between calcium intake and coronary artery calcification has been hindered by a lack of sensitive methodology to monitor early vascular calcium accumulation. The primary study aim was to assess the impact of high calcium intake on coronary artery calcification using innovative calcium tracer kinetic modeling in Ossabaw swine with diet-induced metabolic syndrome. Secondary end points (in vitro wire myography, histopathology, intravascular ultrasound) assessed coronary disease. Methods and Results Pigs (n =24; aged ≈15 months) were fed an atherogenic diet with adequate calcium (0.33% by weight) or high calcium (1.90% from calcium carbonate or dairy) for 6 months. Following 5 months of feeding, all pigs were dosed intravenously with 41Ca, a rare isotope that can be measured in serum and tissues at a sensitivity of 10−18 mol/L by accelerator mass spectrometry. Kinetic modeling evaluated early coronary artery calcification using 41Ca values measured in serial blood samples (collected over 27 days) and coronary artery samples obtained at sacrifice. Serum disappearance of 41Ca and total coronary artery 41Ca accumulation did not differ among groups. Secondary end points demonstrated no treatment differences in coronary artery disease or function. Conclusion There was no detectable effect of high calcium diets (from dairy or calcium carbonate) on coronary artery calcium deposition in metabolic syndrome swine.

Evidence for greater burden of peripheral arterial disease in lower extremity arteries of spinal cord-injured individuals.

Spinal cord injury leads to increased risk for cardiovascular disease and results in greater risk of death. Subclinical markers of atherosclerosis have been reported in carotid arteries of spinal cord-injured individuals (SCI), but the development of lower extremity peripheral arterial disease (PAD) has not been investigated in this population. The purpose of this study was to determine the effect of spinal cord injury on ankle-brachial index (ABI) and intima-media thickness (IMT) of upper-body and lower-extremity arteries. We hypothesized that the aforementioned measures of lower-extremity PAD would be worsened in SCI compared with controls and that regular participation in endurance exercise would improve these in both groups. To test these hypotheses, ABI and IMT were determined in 105 SCI and compared with 156 able-bodied controls with groups further subdivided into physically active and sedentary. ABIs were significantly lower in SCI versus controls (0.96 ± 0.12 vs. 1.06 ± 0.07, P < 0.001), indicating a greater burden of lower-extremity PAD. Upper-body IMTs were similar for brachial and carotid arteries in controls versus SCI. Lower extremity IMTs revealed similar thicknesses for both superficial femoral and popliteal arteries, but when normalized for artery diameter, individuals with SCI had greater IMT than controls in the superficial femoral (0.094 ± 0.03 vs. 0.073 ± 0.02 mm/mm lumen diameter, P < 0.01) and popliteal (0.117 ± 0.04 vs. 0.091 ± 0.02 mm/mm lumen diameter, P < 0.01) arteries. The ABI and normalized IMT of SCI compared with controls indicate that subclinical measures of lower-extremity PAD are worsened in individuals with SCI. These findings should prompt physicians to consider using the ABI as a screening method to detect lower-extremity PAD in SCI.

Circulating Irisin Concentrations Are Associated with a Favourable Lipid Profile in the General Population

Background/aims Irisin is a myokine, which is mainly inversely associated with the risk for non-communicable diseases. Irisin improves cellular energy metabolism by uncoupling the mitochondrial respiratory chain resulting in increased energy expenditure using lipids. To date potential associations between irisin concentration and lipid profile are poorly understood. Therefore, this investigation aimed to evaluate potential associations between irisin and lipid levels in the general population. Methods Data of 430 men and 537 women from the population-based Study of Health in Pomerania (SHIP-TREND) with available irisin and lipid concentrations were used. Analyses of variance, linear and logistic regression models adjusted for age, HBA1c, waist circumference, physical activity, smoking, alcohol consumption, systolic blood pressure, ALAT were calculated. Results We detected significantly inverse associations between irisin and circulating levels of total [beta coefficient 0.21 (standard error 0.08), p = 0.01], low-density cholesterol [-0.16 (0.07), p = 0.03] and triglycerides [-0.17 (0.08), p = 0.02] for men. Females without lipid lowering medication had an inverse association between irisin and total cholesterol [-0.12 (0.06), p = 0.05]. Further, male subjects with irisin concentrations in the third tertile had an increased odds for elevated low-density cholesterol [odds ratio 1.96 (95% confidence interval 1.07–3.48), p = 0.03) and triglyceride [1.95 (1.09–3.47), p = 0.02] levels, even after exclusion of subjects with lipid lowering medication. In addition, our data revealed an annual rhythm of serum irisin levels with peak levels arise in winter and summer months. Conclusion This is the first investigation to report a significant association between circulating irisin and a favourable lipid profile in the general population. This may infer that higher irisin concentrations are associated with a reduced risk for non-communicable diseases.

Mother's exercise during pregnancy programmes vasomotor function in adult offspring

•  What is the central question of this study? Adverse maternal behaviour during pregnancy is well known to have lifelong health consequences for offspring. We asked whether a positive maternal health behaviour may have positive long‐term effects for offspring. Specifically, we investigated whether aerobic maternal exercise improves nitric oxide signalling in femoral arteries of adult swine. •  What is the main finding and its importance? For the first time, a fetal programming outcome due to gestational exercise is reported in adult offspring. Second, contrary to previous speculation regarding the impact of in utero alterations on nitric oxide signalling, our data suggest differential myosin phosphorylation in vascular smooth muscle.

Gene expression differences in healthy brachial and femoral arteries of Rapacz familial hypercholesterolemic swine

The mechanisms underlying the unequal distribution of atherosclerotic disease in the peripheral arteries are currently unclear. Gene expression differences in healthy arteries may influence the heterogeneous distribution of atherosclerosis. Therefore, this investigation compares gene expression in healthy atheroprotected brachial and atherosusceptible femoral arteries of young and disease free Rapacz familial hypercholesterolemic (FHC) swine. We hypothesized that transcripts related to atherosusceptibility would be differentially expressed between these arteries prior to the onset of disease. Femoral and brachial arteries were harvested from four 13-day-old Rapacz FHC swine. No atherosclerotic disease was detected using Sudan IV, Verhoeff-van Gieson, and hematoxylin-eosin staining. Gene expression was quantified using Affymetrix GeneChip Porcine Genome Arrays. An average of 15,552 probe sets had detectable transcripts, while 430 probe sets showed a significant differential expression between arteries (false discovery rate < 0.05). The human orthologs of 63 probe sets with differential expression and a 1.5-fold or greater transcript abundance between arteries are associated with Wnt/β-catenin, lysophospholipid, and Ca-signaling, as well as apoptosis. This is the first investigation reporting that differences in relative abundance of gene expression exist between brachial and femoral arteries in young Rapacz FHC swine prior to the development of atherosclerotic lesions.

Gene expression differences during the heterogeneous progression of peripheral atherosclerosis in familial hypercholesterolemic swine

BackgroundThe heterogeneous progression of atherosclerotic disease in the peripheral arteries is currently not well understood. In humans, artery specific disease progression is partly attributed to the local hemodynamic environments. However, despite similar hemodynamic environments, porcine brachial arteries are protected while femoral arteries are highly susceptible to advanced lesion formation. The aim of this investigation was to determine whether artery specific gene expression patterns contribute to the uneven distribution of peripheral arterial disease (PAD) in Rapacz Familial-Hypercholesterolemic (FHC) swine.ResultsHistological results confirmed rapid atherosclerotic disease progression in femoral but not brachial arteries. A total of 18,922 probe sets had sufficient signal abundance. A main effect for age and artery was observed for 1784 and 1256 probe sets, respectively. A significant age x artery interaction was found for 184 probe sets. Furthermore, comparison between arteries found a decrease from 714 to 370 differentially expressed transcripts from nine months to two years of age. Gene ontology analysis of the 56 genes with a main effect for artery and an age x artery interaction identified vascular smooth muscle contraction as enhanced biological signaling pathway.ConclusionThis is the first investigation to report that the total number of differential genes decreases with diverging atherosclerotic disease pattern between porcine brachial and femoral arteries.

Changes in Body Weight and Composition Are Associated With Changes in Left Ventricular Geometry and Function in the General PopulationCLINICAL PERSPECTIVE: SHIP (Study of Health in Pomerania)

Background— The different effects of total body weight (TBW), fat-free mass (FFM), and fat mass (FM) on left ventricular (LV) geometry and function are complex. We investigated the associations of changes over time in TBW, FM, and FFM with changes in LV geometry and function. Methods and Results— We analyzed data from 1189 subjects (694 women), aged 44 to 86 years, from the baseline and the 5-year follow-up examination of the population-based SHIP (Study of Health in Pomerania). TBW was measured, and FFM and FM were calculated based on height-weight models derived from bioelectrical impedance studies. Echocardiographic measurements of LV geometry and function were performed according to the guidelines of the American Society of Echocardiography. Changes in body composition measures were associated with changes in LV geometry and function by multivariable-adjusted linear regression models. A 1-kg increase/decrease in TBW or FM was associated, respectively, with an increase/decrease of 0.89 g or 1.84 g in LV mass, whereas there was no such association on changes in FFM. Moreover, an increase in FM was associated with LV concentric remodeling and impairment of systolic and diastolic function parameters, whereas an increase in FFM was associated with LV eccentric remodeling and improved systolic and diastolic functional variables. Conclusions— Our findings indicate that changes in LV morphology and function depend on the type of body mass composition. Prospective data need to address whether specific changes in body composition over time may affect the risk for heart dysfunction more precisely than the change in TBW.

Reference intervals for serum sphingosine-1-phosphate in the population-based Study of Health in Pomerania

BACKGROUND The bioactive signaling lipid sphingosine-1-phosphate (S1P) is a potential biomarker for cardiovascular disease (CVD). To date, no reference intervals for S1P have been defined. This study aims to establish a reference range for serum S1P in healthy individuals. METHODS We determined reference intervals for S1P levels according to gender and age in a sample of 1339 healthy participants of the Study of Health in Pomerania (SHIP)-TREND cohort after exclusion of subjects with CVD, diabetes mellitus, hypertension, metabolic syndrome, elevated liver enzymes, chronic kidney disease stadium III or IV, or body mass index (BMI)>30kg/m2. Serum S1P was measured by liquid chromatography-tandem mass spectrometry. RESULTS The median age of the participants was 41 (25th; 75th percentile 32; 51) years, 65% were women. The median serum concentration of S1P was 0.804 (0.694; 0.920) μmol/L. No association with gender and age was observed. The overall reference interval was 0.534-1.242μmol/L (2.5th; 97.5th percentile). Further exclusion of smokers, individuals with BMI>25kg/m2 or elevated lipid levels did not significantly affect median S1P concentrations. CONCLUSIONS This study provides reference intervals for serum S1P in healthy individuals. Total serum S1P concentrations vary irrespectively of age, gender, BMI or smoking status.

Statins are related to impaired exercise capacity in males but not females

Background Exercise and statins reduce cardiovascular disease (CVD). Exercise capacity may be assessed using cardiopulmonary exercise testing (CPET). Whether statin medication is associated with CPET parameters is unclear. We investigated if statins are related with exercise capacity during CPET in the general population. Methods Cross-sectional data of two independent cohorts of the Study of Health in Pomerania (SHIP) were merged (n = 3,500; 50% males). Oxygen consumption (VO2) at peak exercise (VO2peak) and anaerobic threshold (VO2@AT) was assessed during symptom-limited CPET. Two linear regression models related VO2peak with statin usage were calculated. Model 1 adjusted for age, sex, previous myocardial infarction, and physical inactivity and model 2 additionally for body mass index, smoking, hypertension, diabetes and estimated glomerular filtration rate. Propensity score matching was used for validation. Results Statin usage was associated with lower VO2peak (no statin: 2336; 95%-confidence interval [CI]: 2287–2,385 vs. statin 2090; 95%-CI: 2,031–2149 ml/min; P < .0001) and VO2@AT (no statin: 1,172; 95%-CI: 1,142–1,202 vs. statin: 1,111; 95%-CI: 1,075–1,147 ml/min; P = .0061) in males but not females (VO2peak: no statin: 1,467; 95%-CI: 1,417–1,517 vs. statin: 1,503; 95%-CI: 1,426–1,579 ml/min; P = 1.00 and VO2@AT: no statin: 854; 95%-CI: 824–885 vs. statin 864; 95%-CI: 817–911 ml/min; P = 1.00). Model 2 revealed similar results. Propensity scores analysis confirmed the results. Conclusion In the general population present statin medication was related with impaired exercise capacity in males but not females. Sex specific effects of statins on cardiopulmonary exercise capacity deserve further research.