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1.
J Surg Res ; 235: 410-423, 2019 03.
Article in English | MEDLINE | ID: mdl-30691823

ABSTRACT

BACKGROUND: Gastrointestinal blood flow may be compromised during and after vasopressor support. Endothelin expression may lead to microcirculatory dysfunction. The aim of this study was to analyze the effect of vasopressin and dobutamine after mesenteric ischemia on the gastrointestinal mucosal microcirculation, endothelin expression, and morphologic injury. MATERIALS AND METHODS: Pigs were studied in four groups (six pigs in each group): 1, sham; 2-4 ischemia (1 h superior mesenteric artery occlusion with 30 min reperfusion and 30 min of vehicle [2], dobutamine [3], or vasopressin [4] administration, followed by 30-min break and thiopental-induced hypotension [3, 4]). Blood flow of the gastric, jejunal, and rectosigmoidal mucosa was measured. At the end of the experiment, the mucosal expression of endothelin-1 (ET-1) and its receptor subtypes A (ETA) and B were determined by polymerase chain reaction. Mucosal injury, apoptotic cell death, and leukocytic infiltration were determined by histology and immunohistochemical analysis of cleaved caspase-3 and myeloperoxidase. RESULTS: Mesenteric ischemia increased jejunal mucosal ET-1 gene expression, arterial ET-1, intestinal fatty acid binding protein, and jejunal mucosal injury compared with sham. Dobutamine increased arteriovenous shunting at the cost of the jejunal mucosal blood perfusion. This was associated with an increased expression of ET-1 and ETA and mucosal leukocytic infiltration. In contrast, vasopressin increased postischemic capillary density and tissue blood flow. This was associated with a lower ET-1 gene expression. Vasopressin did not induce jejunal mucosal leukocytic infiltration. CONCLUSIONS: Vasopressin reduces mesenteric ischemia-associated alterations of the microcirculation and tissue integrity, whereas dobutamine does not.


Subject(s)
Adrenergic beta-1 Receptor Agonists/therapeutic use , Dobutamine/therapeutic use , Mesenteric Ischemia/drug therapy , Vasoconstrictor Agents/therapeutic use , Vasopressins/therapeutic use , Adrenergic beta-1 Receptor Agonists/pharmacology , Animals , Dobutamine/pharmacology , Drug Evaluation, Preclinical , Endothelin-1/blood , Fatty Acid-Binding Proteins/blood , Intestinal Mucosa/blood supply , Intestinal Mucosa/drug effects , Mesenteric Ischemia/blood , Microcirculation/drug effects , Swine , Vasoconstrictor Agents/pharmacology , Vasopressins/pharmacology
2.
Gynecol Endocrinol ; 33(4): 292-296, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28010148

ABSTRACT

The prevalence of osteoporosis in Sub-Saharan African (SSA) countries is low, however, as urbanization takes root, it is predicted that bone health will decrease dramatically. The bone health of the semi-nomadic Ovahimba people of Namibia was investigated in the context of urbanization and changes of the sociocultural environment. Furthermore, data on bone health in SSA countries is scarce; there exists no ethnic-specific reference group for people of black origin. Included in the study were 98 urban and rural living Ovahimba people. Quantitative ultrasound was performed, sunrise/sunset saliva cortisol concentrations was measured and a questionnaire was conducted. There was no significant difference in the QUS parameters, however, after adjustment for confounders, SOS and SI differed significantly. The saliva cortisol concentrations differed significantly. After adjustment for confounders, saliva cortisol was significantly negatively correlated to SOS (r= -0.27, p = 0.021) giving an indication for an association between cortisol concentration and QUS parameters. The urban group furthermore showed a nutritional transition. Even though the bone health of the Ovahimba is very good, first signs of the adverse effects of urbanization were detected. Beside changes of lifestyle, this may be attributed to an increased cortisol exposure of the Ovahimba people living in an urban environment due to an increased psychosocial stress.


Subject(s)
Bone Density/physiology , Bone and Bones/diagnostic imaging , Hydrocortisone/analysis , Life Style , Urbanization , Adult , Female , Humans , Male , Middle Aged , Namibia , Risk Factors , Saliva/chemistry , Ultrasonography
3.
Eur Surg Res ; 54(1-2): 75-86, 2015.
Article in English | MEDLINE | ID: mdl-25377352

ABSTRACT

BACKGROUND/AIM: Upper gastrointestinal bleeding (UGIB) is one of the most frequent gastrointestinal complications after cardiac surgery with cardiopulmonary bypass (CPB). Endothelin expression and microcirculatory dysfunction have been shown to be involved in UGIB. The aim of this study was to analyze the effect of vasopressin during CPB on the gastric mucosal microcirculation and the involvement of the endothelin system. METHODS: Eighteen pigs were randomized into three groups (n = 6 each): group I = sham, group II = CPB (1-hour CPB) and group III = CPB + vasopressin (1-hour CPB and vasopressin administration during CPB to maintain baseline arterial pressure). All animals were observed for a further 90 min after termination of CPB. Systemic hemodynamics as well as blood flow and oxygen saturation of the gastric mucosa were measured continuously. At the end of the experiment, the gastric mucosal expressions of endothelin-1 (ET-1) and its receptor subtypes A (ET(A)) and B (ET(B)) were determined by polymerase chain reaction. Gastric mucosal injury, apoptotic cell death and leukocytic infiltration were determined by histology and immunohistochemical analyses of cleaved caspase-3 and myeloperoxidase. RESULTS: CPB decreased gastric microvascular perfusion, which was associated with an increased expression of ET-1 and ET(A). Vasopressin aggravated the CPB-associated malperfusion, whereas it completely abrogated the upregulation of ET-1 and ET(A). Interestingly, vasopressin did not induce gastric mucosal morphologic injury, leukocytic infiltration or apoptotic cell death. CONCLUSION: Vasopressin aggravates CPB-associated microvascular malperfusion of the gastric mucosa but does not induce gastric mucosal injury.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Gastric Mucosa/blood supply , Ischemia/etiology , Vasoconstrictor Agents/adverse effects , Vasopressins/adverse effects , Animals , Endothelins/metabolism , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Hemodynamics , Ischemia/metabolism , Microcirculation/drug effects , Random Allocation , Swine
4.
J Clin Endocrinol Metab ; 100(3): E482-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25522263

ABSTRACT

CONTEXT: Diabetes mellitus is increasingly affecting Africa. OBJECTIVE: Urbanization of the Ovahimba people in Namibia is associated with an increased prevalence of disorders of glucose metabolism, and may thus be attributed to changes of cortisol homeostasis. DESIGN: A prospective, cross-sectional, diagnostic study was applied. SETTING: The study was conducted in the field. Location of the Diabetes Epidemic: Africa and Namibia. PARTICIPANTS: Ovahimba people: group 1 "urban" n = 60, 42 females, 46.3 ± 11.3 years (town); group 2 "rural" n = 63, 44 females, 51.1 ± 12.0 years (seminomadic). INTERVENTIONS: oGTT, sunrise and sunset saliva cortisol, metabolic parameters, questionnaire. MAIN OUTCOME MEASURE: The prevalence of disorders of glucose metabolism (DM, IGT, IFT). RESULTS: The prevalence of disorders of glucose metabolism differed significantly: urban group n = 17(28.3%) vs rural group n = 8(12.7%) (P = 0.04). The saliva cortisol concentrations also differed significantly: sunrise 0.34 ± 0.18 vs 0.12 ± 0.15 µg/dL, sunset 0.18 ± 0.20 vs 0.07 ± 0.09 µg/dL, area under the curve 6.16 ± 3.48 vs 2.28 ± 2.56 µg/dL * 24 h (all P < 0.001). Further metabolic parameters were unfavorably changed in the urban group: hip circumference (P < 0.001), waist circumference (P < 0.001), body mass index (P = 0.014), systolic BP at rest (P < 0.001), diastolic BP at rest (P = 0.002), systolic BP after exercise (P < 0.001), heart rate after exercise (P = 0.007), fasting glucose (P < 0.001), 2-h-glucose by OGTT (P = 0.002), triglycerides (P = 0.04), HDL-cholesterol (P = 0.014), prevalence of the metabolic syndrome (P < 0.001). Physical activity was higher in the rural group, and intake of fast food and sweets were higher in the urban group. CONCLUSIONS: Urbanization of the Ovahimba people is associated with an increasing prevalence of disorders of glucose metabolism and other unfavorable metabolic parameters. Besides changes of lifestyle, this may be attributed to an increased cortisol exposure of the Ovahimba people living in an urban environment.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Hydrocortisone/metabolism , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Social Environment , Adult , Cross-Sectional Studies , Culture , Developing Countries/statistics & numerical data , Female , Homeostasis , Humans , International Cooperation , Male , Middle Aged , Namibia/epidemiology , Namibia/ethnology , Prevalence , Risk Factors , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data
5.
J Thorac Cardiovasc Surg ; 145(2): 539-47, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22551769

ABSTRACT

OBJECTIVE: Gastrointestinal blood flow can be compromised during and after cardiopulmonary bypass. Endothelin has been shown to be involved in the intestinal microcirculatory disturbance of sepsis. The aim of the present study was to analyze the involvement of the endothelin system on intestinal blood flow regulation during cardiopulmonary bypass and the effect of vasopressin given during cardiopulmonary bypass. METHODS: A total of 24 pigs were studied in 4 groups (n = 6): group I, sham; group II, ischemia/reperfusion with 1 hour of superior mesenteric artery occlusion; group III, cardiopulmonary bypass for 1 hour; and group IV, 1 hour of cardiopulmonary bypass plus vasopressin administration, maintaining the baseline arterial pressure. All the pigs were reperfused for 90 minutes. During the experiment, the hemodynamics and jejunal microcirculation were measured continuously. The jejunal mucosal expression of endothelin-1 and its receptor subtypes A and B were determined using polymerase chain reaction. RESULTS: During cardiopulmonary bypass, superior mesenteric artery flow was preserved but marked jejunal microvascular impairment occurred compared with baseline (mucosal capillary density, 192.2 ± 5.4 vs 150.8 ± 5.1 cm/cm(2); P = .005; tissue blood flow, 501.7 ± 39.3 vs 332.3 ± 27.9 AU; P = .025). The expression of endothelin-1 after cardiopulmonary bypass (3.2 ± 0.4 vs 12.2 ± 0.8 RQ, P = .006) and endothelin subtype A (0.7 ± 0.2 vs 2.4 ± 0.6 RQ; P = .01) was significantly increased compared to the sham group. Vasopressin administration during cardiopulmonary bypass led to normal capillary density (189.9 ± 3.9 vs 178.0 ± 6.3; P = .1) and tissue blood flow (501.7 ± 39.3 vs 494.7 ± 44.4 AU; P = .4) compared with baseline. The expression of endothelin-1 (3.2 ± 0.4 vs 1.8 ± 0.3 RQ; P = .3) and endothelin subtype A (0.7 ± 0.2 vs 0.9 ± 0.2 RQ; P = .5) was not different from the sham group. CONCLUSIONS: Cardiopulmonary bypass leads to microvascular impairment of jejunal microcirculation, which is associated with the upregulation of endothelin-1 and endothelin subtype A. The administration of vasopressin minimizes these cardiopulmonary bypass-associated alterations.


Subject(s)
Capillaries/drug effects , Cardiopulmonary Bypass , Endothelin-1/metabolism , Jejunum/blood supply , Mesenteric Artery, Superior/drug effects , Microcirculation/drug effects , Splanchnic Circulation/drug effects , Vasopressins/pharmacology , Animals , Biopsy , Blood Flow Velocity/drug effects , Capillaries/metabolism , Cardiopulmonary Bypass/adverse effects , Endothelin-1/genetics , Ischemia/etiology , Ischemia/metabolism , Ischemia/physiopathology , Ischemia/prevention & control , Mesenteric Artery, Superior/metabolism , Mesenteric Ischemia , Models, Animal , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Receptor, Endothelin A/genetics , Receptor, Endothelin A/metabolism , Receptor, Endothelin B/genetics , Receptor, Endothelin B/metabolism , Regional Blood Flow/drug effects , Sus scrofa , Time Factors , Vascular Diseases/etiology , Vascular Diseases/metabolism , Vascular Diseases/physiopathology , Vascular Diseases/prevention & control
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