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Biomedical subjects

Peter Friberg

Publications and source records attributed to Peter Friberg.

At least 37 records · Page 2Linked to original sources
PubMed2005

Decreased renal sympathetic activity in response to cardiac unloading with nitroglycerin in patients with heart failure.

AIMS: To examine changes in renal sympathetic outflow in response to cardiac unloading with nitroglycerin (GTN) in patients with chronic heart failure (CHF) and healthy subjects (HS). METHODS AND RESULTS: Renal (RNAsp) and total body (TBNAsp) noradrenaline (NA) spillover were measured with radiotracer methods in 16 patients with CHF (50+/-3 years, LVEF 20+/-1%) and nine HS (57+/-2 years) during right heart and renal vein catheterisation. Low dose GTN decreased mean pulmonary artery pressure (PAm: CHF -7+/-2 mm Hg, HS -4+/-1 mm Hg, p<0.05 vs. baseline) but not mean arterial pressure (MAP: CHF -2+/-1 mm Hg, HS -2+/-1 mm Hg) and did not affect RNAsp in any of the study groups. High dose GTN lowered MAP (CHF -12+/-1 mm Hg, HS -12+/-2 mm Hg, p<0.05 vs. baseline) and PAm (CHF -13+/-2 mm Hg, HS -5+/-1 mm Hg, p<0.05 vs. baseline) and was accompanied by a significant reduction in RNAsp only in CHF (1.3+/-0.1 nmol/min baseline to 0.9+/-0.2 nmol/min, p<0.05), whereas RNAsp in HS remained unchanged. CONCLUSIONS: In spite of a reduction in both arterial pressure and cardiac filling pressures, renal sympathetic activity decreased in CHF and did not increase in HS. These findings suggest that the altered loading conditions resulting from high-dose GTN infusion have renal sympathoinhibitory effects.

Analysis of Variance↗
PubMed2005

Blunted vascular response to endothelin-a receptor blockade in cyclosporine-treated lung transplant recipients.

BACKGROUND: The majority of cyclosporine-treated transplant recipients develop hypertension. Endothelin-1 (ET-1) has been suggested to mediate cyclosporine-induced vasoconstriction when binding to ET-A receptors. We hypothesized that cyclosporine-treated lung transplant recipients have an increased basal vascular resistance and an augmented response to ET-A receptor blockade. METHODS: The selective ET-A receptor blocker BQ-123 (10 and 50 nmol/min) was infused into the brachial artery, alone or in combination with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) (2 and 4 micromol/min) in 10 lung transplant recipients without pharmacologically treated hypertension and 8 healthy controls. Forearm blood flow (FBF) was measured by venous occlusion plethysmography and plasma levels of ET-1 were analyzed. RESULTS: Baseline forearm vascular resistance did not differ between recipients and controls (32 +/- 4 vs 42 +/- 7 mmHg/ml/min, p = 0.32). BQ-123 increased FBF in controls but not in recipients (26% +/- 9% vs 5% +/- 11% at 10 nmol/min, p = 0.043 between groups). Coinfusion of BQ-123 and L-NMMA caused a comparable decrease in FBF in recipients and controls (-26% +/- 11%, vs -34% +/- 7%). Baseline ET-1 was higher in recipients (17.2 +/- 1.1 vs 14.7 +/- 0.8 pg/ml, p = 0.038). BQ-123 infusion increased plasma ET-1 in controls but not in recipients (+24% +/- 11% vs -0.4% +/- 6.2%, p = 0.029 between groups). CONCLUSIONS: The results demonstrate that cyclosporine-treated lung transplant recipients have increased plasma levels of ET-1 and a blunted response to ET-A receptor blockade compared with healthy subjects. In contrast, we found no evidence for an increased basal vascular resistance in transplant recipients. These alterations in endothelin handling may contribute to the development of transplant-associated hypertension.

Adult↗
PubMed2005

Increased myocardial repolarization lability and reduced cardiac baroreflex sensitivity in individuals with high-normal blood pressure.

BACKGROUND: Recent guidelines for the management of arterial hypertension have proposed that, to prevent cardiovascular disease, lifestyle modifications are required even in the case of high-normal blood pressure (HNBP). OBJECTIVE: To assess myocardial repolarization and spontaneous cardiac baroreflex sensitivity (BRS) in newly diagnosed and never-treated individuals. DESIGN AND PARTICIPANTS: We studied healthy individuals with HNBP according to the 2003 European Society of Hypertension-ESC guidelines and, for comparison, patients with renovascular hypertension (RVH) and healthy individuals with normal blood pressure (NBP). MAIN OUTCOME MEASURES: Electrocardiogram and beat-to-beat blood pressure were recorded and spontaneous cardiac baroreflex sensitivity and the temporal QT interval variability index (QTVI) were calculated. RESULTS: Individuals with HNBP had increased QTVI values compared with those with NBP (-1.23 +/- 0.37 compared with -1.52 +/- 0.26; P < 0.05), whereas patients with RVH had additionally increased QTVI values that were greater than those in healthy individuals with NBP or HNBP (-0.81 +/- 0.75; P < 0.05 compared with both groups). BRS was reduced in both groups of individuals with increased blood pressures compared with NBP (8.2 +/- 4.1 ms/mmHg for individuals with HNBP, 6.1 +/- 4.3 ms/mmHg for patients with RVH and 10.8 +/- 3.5 ms/mmHg for NBP; P < 0.05 for both). CONCLUSION: In otherwise healthy individuals, even a moderate blood pressure increase is associated with increased myocardial repolarization lability and reduced baroreflex sensitivity (BRS). Patients with RVH have an additionally increased QTVI, with values similar to those reported in congestive heart failure. Future studies are needed to establish the value of QTVI and BRS measurements among individuals with HNBP in predicting the risk of progression to hypertension and end-organ damage.

Aged↗
PubMed2005

Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjects.

BACKGROUND: The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. METHODS: A total of 102 healthy volunteers (12-81 years, 53 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents <20 years, adults > or = 20 years). The influence of haemodynamic factors, exercise, and demographic factors on LVM were determined with multivariate linear regression. RESULTS: LVM rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188 +/- 22 g versus 139 +/- 21 g, P < 0.001; LVMBSA: 94 +/- 11 g m(-2) versus 80 +/- 11 g m(-2), P < 0.001) and in adolescents when adjusted for BSA (LVM: 128 +/- 29 g versus 107 +/- 20 g, P = 0.063; LVMBSA: 82 +/- 8 g m(-2) versus 71 +/- 10 g m(-2), P = 0.025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender, and BSA as the major determinants of LVM (global R2 = 0.69). CONCLUSIONS: Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age, and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise, and wall stress were not.

Adolescent↗
PubMed2004

Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle.

Pharmacological interruption of angiotensin II type 1 (AT(1)) receptor signaling during nephrogenesis in rats perturbs renal tubular development. Perturbed tubulogenesis may contribute to long-term impairment of urinary concentrating ability, which is the main functional irreversible defect. The aim of this study was to further characterize tubular developmental deficits in neonatal rats, focusing on the thick ascending limb of Henle (TALH), known to undergo profound developmental changes and to be involved in urine-concentrating mechanisms. We have carried out immunohistochemistry and Western immunoblotting using antibodies directed against the major histocompatibility complex class II (MHC II) molecule and different TALH-specific markers, namely, cyclooxygenase-2 (COX-2), Tamm-Horsfall glycoprotein (THP), and the bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (BSC-1/NKCC2). Immunohistochemistry demonstrated expression of MHC II, COX-2, THP, and BSC-1/NKCC2 proteins in normally developing TALH cells. The AT(1)-receptor antagonist losartan abolished MHC II expression exclusively in the developing TALH cells. Increased expression of COX-2 and THP was observed in the TALH cells of losartan-treated rats. Western immunoblotting confirmed increases in cortical and medullary COX-2 and THP abundance and revealed a decrease in cortical BSC-1/NKCC2 abundance in response to losartan treatment. We conclude that neonatal losartan treatment causes significant changes in the phenotype of the developing TALH in the rat.

Animals↗
PubMed2004

Effects of a Mediterranean-inspired diet on blood lipids, vascular function and oxidative stress in healthy subjects.

Mediterranean-inspired diets have been shown to decrease cholesterol levels in patients with hypercholesterolaemia, who frequently exhibit endothelial dysfunction. The aims of the present study are to improve endothelial function by dietary intervention in healthy subjects with lipid levels representative of a Western population. Twenty-two healthy subjects (mean total cholesterol, 5.6 mmol/l) were given a Mediterranean-inspired diet rich in omega-3 fatty acids and sterol esters, but low in saturated fat, or an ordinary Swedish diet, for 4 weeks in a randomized cross-over study. The composition of the diets were: in the Swedish diet, 2090 kcal (where 1 kcal=4.184 kJ; 48% of energy from carbohydrate, 15% from protein and 36% from fat) and 19 g of fibre; in the Mediterranean-inspired diet, 1869 kcal (48% of energy from carbohydrate, 16% from protein, 34% from fat) and 40 g of fibre. After each dietary period, fasting blood lipids, insulin and glucose levels, as well as apo B (apolipoprotein B) and LDL (low-density lipoprotein) particle size, were analysed. Endothelial-dependent and -independent vasodilation was measured invasively by venous occlusion plethysmography, and arterial distensibility was assessed by echocardiography tracking. Fibrinolytic capacity across the forearm, as well as oxidative stress measured through urinary F(2)-isoprostane, were evaluated. Total, LDL- and apo B-cholesterol and triacylglycerol (triglyceride) concentrations were decreased by 17%, 22%, 16% and 17% respectively, after the Mediterranean-inspired diet compared with the Swedish diet ( P <0.05 for all). However, no differences in plasma concentrations of insulin and glucose and LDL particle size, endothelial function, arterial distensibility, fibrinolytic capacity or oxidative stress were detected. Treatment for 4 weeks with a Mediterranean-inspired diet decreased blood lipids in healthy individuals with a low-risk profile for cardiovascular disease. This beneficial effect was not mirrored in vascular function or oxidative stress evaluation.

Adult↗
PubMed2004

Elevated temporal QT variability index in patients with chronic renal failure.

Patients with CRF (chronic renal failure) are at increased risk of cardiovascular diseases, and 60% of cardiovascular mortality in CRF is attributed to sudden death. Various abnormalities in myocardial repolarization are associated with the risk of ventricular arrhythmia. The aim of this study was to evaluate an index of temporal myocardial repolarization lability, the temporal QTVI (QT variability index), in patients with CRF. ECGs were recorded in 153 patients with CRF on haemodialysis (n=67), continuous ambulatory peritoneal dialysis (n=43) or conservative treatment (n=43) during 30 min of rest. QTVI was calculated as the logarithm of the ratio between the variances of the normalized QT and RR intervals. Age-matched healthy subjects (n=39) were examined for comparison. QTVI was increased by 47% in CRF patients compared with healthy subjects (-0.82+/-0.56 compared with -1.54+/-0.27 respectively; P<0.01). QTVI did not differ among patients on dialysis or conservative treatment, whereas QTVI was elevated further in patients with diabetes compared with non-diabetic CRF patients (-0.56+/-0.54 compared with -0.94+/-0.52 respectively; P<0.01). In a multiple linear regression analysis, diabetes and a history of coronary artery disease were the only independent predictors of QTVI in the CRF population. The present study demonstrates that elevated QTVI in patients with CRF is associated with diabetes and coronary disease. The present findings are important given that repolarization instability may predispose to ventricular arrhythmia and sudden death, events that occur frequently in CRF patients.

Adult↗
PubMed2004

Neonatal ACE inhibition in rats interferes with lung development.

The renin-angiotensin system (RAS) is developmentally up-regulated and it is essential for kidney development in several species. Given the fact that the rat lung undergoes postnatal development, the mammalian lung possesses the highest angiotensin-converting enzyme (ACE) levels and ACE activity increases during the first weeks postpartum, we tested the hypothesis that ACE inhibition influences postnatal lung development. Rats were given the ACE inhibitor enalapril (10 mg kg(-1)) from 0 to 9 days of age and their lungs were examined at day 4 and 9. Lung structure was evaluated by means of light microscopy, and surface tension of bronchoalveolar lavage fluid was measured by means of a Wilhelmy balance. Neonatal ACE inhibition lowered the surface tension of bronchoalveolar lavage fluid and caused widening of respiratory airspaces and thinning of alveolar septa. Our results suggest that early postnatal ACE inhibition in rats interferes with lung development.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Neonatal losartan treatment suppresses renal expression of molecules involved in cell-cell and cell-matrix interactions.

Lack of neonatal angiotensin II type 1 receptor (AT(1)) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT(1) receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, approximately 30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, alpha-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin alpha6 and caused relocalization of integrins alpha6 and alpha3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT(1) receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and alpha-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.

Actins↗
PubMed2004

Increased arterial stiffness in cyclosporine-treated lung transplant recipients early after transplantation.

BACKGROUND: The majority of patients undergoing solid organ transplantation develop hypertension, to which cyclosporine (CsA)-induced peripheral vasoconstriction may contribute. We hypothesized that CsA-treated transplant recipients have an increased basal vascular tone and an altered response to nitric oxide. To test this hypothesis arterial resistance, non-endothelial dependent relaxation and arterial stiffness were investigated in CsA-treated lung transplant recipients within 18 months after transplantation. METHODS: In study 1, forearm blood flow (FBF) was measured by venous occlusion plethysmography at baseline and during glyceryl trinitrate (GTN) and N(G)-monomethyl-l-arginine acetate (l-NMMA) infusion in seven lung transplant recipients and nine healthy subjects. In study 2, arterial stiffness in carotid (CCA) and radial artery (RA) was measured by ultrasound (echo-tracking) in 10 lung transplant recipients, 12 healthy subjects and six patients waiting for lung transplantation. RESULTS: Basal FBF (3.1 +/- 0.2 vs. 3.0 +/- 0.3 mL/min, p = 0.79) and forearm arterial resistance (36 +/- 3 vs. 33 +/- 3 mmHg/mL/min, p = 0.60) did not differ between transplant recipients and controls. GTN infusion increased and l-NMMA decreased blood flow equally in both groups. Transplant recipients had increased arterial stiffness compared to both pre-transplant patients and healthy subjects (CCA stiffness index 11.7 +/- 1.1 vs. 8.5 +/- 0.2 and 8.6 +/- 0.6, p < 0.05 both; RA stiffness index 14.7 +/- 1.5 vs. 8.9 +/- 1.3 and 10.6 +/- 0.7, p < 0.05 both). CONCLUSIONS: Forearm blood flow and arterial resistance did not differ between healthy subjects and cyclosporine-treated lung transplant recipients early after transplantation. Increased arterial stiffness was demonstrated in transplant recipients, which may have implications for future development of transplant hypertension.

Adult↗
PubMed2003

Growth hormone aggravates renal abnormalities induced by neonatal enalapril treatment.

Lack of neonatal angiotensin II type-1 receptor stimulation produces irreversible abnormalities of renal function and morphology, which can be prevented by simultaneous administration of insulin-like growth factor-I (IGF-I). Given the fact that growth hormone (GH) is the strongest secretagogue for IGF-I, we wanted to explore whether GH could reproduce the effect of IGF-I. Rats were treated from 3 to 13 days of age with the angiotensin-converting enzyme inhibitor enalapril (10 mg/kg/day) and GH (4 mg/kg/day), alone or in combination. Renal gene expression of IGF-I and IGF-binding proteins (IGFBP) was determined during and after treatment. Renal function and morphology were investigated at adult age. In contrast to the beneficial effect of IGF-I, GH treatment in combination with enalapril further deteriorated both renal function and morphology as compared with enalapril treatment alone, demonstrating: reduced glomerular filtration rate, increased tubular dilation and further expansion of the outer medulla. Enalapril decreased medullary expression of IGF-I and increased renal expression of IGFBP-1, changes that were not affected by concomitant GH treatment. These findings indicate that GH and IGF-I have different roles in the renin-angiotensin system-mediated kidney development.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Perturbed medullary tubulogenesis in neonatal rat exposed to renin-angiotensin system inhibition.

BACKGROUND: Pharmacological interruption of the angiotensin II type-1 receptor (AT(1)) signalling during nephrogenesis in rats induces irreversible abnormalities in kidney morphology, comprising papillary atrophy and tubulointerstitial damage, which are characterized by tubular dilatation/atrophy and interstitial inflammation/fibrosis. This study determined the time course for development of tubular structural and inflammatory changes and possible cytokine production in the renal medulla of newborn rats exposed to angiotensin-converting enzyme (ACE) inhibition. Additionally, medullary expression of E-cadherin, a marker for tubular formation, was investigated in ACE-inhibited rats. METHODS: Newborn rats were exposed (postnatal days 0-12) to ACE inhibitor enalapril and killed at days 1, 2, 4, 9 and 13. One kidney was used for morphological evaluation and the other for immunohistochemistry, using antibodies directed against monocytes/macrophages, T cells and E-cadherin on frozen sections. In a separate experiment, rats were treated for 9 days and had their kidneys processed for western immunoblot and immunohistochemistry, where antibodies directed against monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor-alpha (TNF-alpha) were used on paraffin sections. RESULTS: In renal medulla from enalapril-treated rats, volume fractions of tubular lumens and interstitium were increased from postnatal days 2 and 4, respectively, while that of tubular cells was decreased from 4 days of age. Concomitant loss and/or reduction in E-cadherin expression (from day 2) was observed in dilated medullary tubules of enalapril-treated rats. Furthermore, in the medulla of enalapril-treated rats, the increased number of ED2+ (resident macrophages) cells, followed by the increase in ED1+ (monocytes/macrophages) and CD4+ T cells, was observed at days 9 and 13, respectively. This was accompanied by increased medullary expression of TNF-alpha at day 9. CONCLUSIONS: Neonatal ACE inhibition perturbs medullary tubulogenesis, as indicated by tubular dilatation and a lack of E-cadherin expression in these tubules. Macrophage/monocyte-mediated immune response is a secondary event, coincidentally associated with the up-regulation of TNF-alpha.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Regional norepinephrine spillover in response to angiotensin-converting enzyme inhibition in healthy subjects.

OBJECTIVES: Even though most previous studies have shown that central nervous angiotensin II causes sympatho-excitation, there are data suggesting that blockade of the renin-angiotensin system (RAS) could activate the renal sympathetic nerves. The aim of the present study was to investigate overall, cardiac and renal sympathetic nerve activity, before and after intravenous enalaprilat, in healthy normotensive subjects without an activated RAS. METHODS: Thirty healthy subjects underwent catheterization of the radial artery, right renal and coronary sinus veins with blood sampling at baseline and 30-40 min after 1.25 or 2.5 mg of intravenous enalaprilat, respectively. Regional and overall sympathetic nervous activity was estimated using isotope dilution, calculating spillovers of norepinephrine. RESULTS: Mean arterial blood pressure decreased by 5% (P < 0.05) after the higher dose and remained unchanged after the lower dose of enalaprilat, whereas renal norepinephrine spillover increased after both doses by 49 and 26% respectively (P < 0.05 for both). Cardiac and total body norepinephrine spillover remained unchanged after both doses of enalaprilat. Pulmonary capillary wedge pressure, which was measured in eight subjects after 2.5 mg enalaprilat, fell by 43% (P < 0.05). CONCLUSIONS: In the absence of, or after a minor, blood pressure fall, intravenous enalaprilat selectively activates the renal nerves in healthy subjects without an activated RAS. Unloading of the low-pressure baroreceptor system and/or a central nervous effect of enalaprilat may be responsible for this differentiated sympathetic nervous response.

Adult↗
PubMed2003

Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results.

Measurements of plasma normetanephrine and metanephrine provide a highly sensitive test for diagnosis of pheochromocytoma, but false-positive results remain a problem. We therefore assessed medication-associated false-positive results and use of supplementary tests, including plasma normetanephrine responses to clonidine, to distinguish true- from false-positive results. The study included 208 patients with pheochromocytoma and 648 patients in whom pheochromocytoma was excluded. Clonidine-suppression tests were carried out in 48 patients with and 49 patients without the tumor. Tricyclic antidepressants and phenoxybenzamine accounted for 41% of false-positive elevations of plasma normetanephrine and 44-45% those of plasma and urinary norepinephrine. High plasma normetanephrine to norepinephrine or metanephrine to epinephrine ratios were strongly predictive of pheochromocytoma. Lack of decrease and elevated plasma levels of norepinephrine or normetanephrine after clonidine also confirmed pheochromocytoma with high specificity. However, 16 of 48 patients with pheochromocytoma had normal levels or decreases of norepinephrine after clonidine. In contrast, plasma normetanephrine remained elevated in all but 2 patients, indicating more reliable diagnosis using normetanephrine than norepinephrine responses to clonidine. Thus, in patients with suspected pheochromocytoma and positive biochemical results, false-positive elevations due to medications should first be eliminated. Patterns of biochemical test results and responses of plasma normetanephrine to clonidine can then help distinguish true- from false-positive results.

Adrenal Gland Neoplasms↗
PubMed2002

Biochemical diagnosis of pheochromocytoma: which test is best?

CONTEXT: Diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor. However, the best test to establish the diagnosis has not been determined. OBJECTIVE: To determine the biochemical test or combination of tests that provides the best method for diagnosis of pheochromocytoma. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cohort study of patients tested for pheochromocytoma at 4 referral centers between 1994 and 2001. The analysis included 214 patients in whom the diagnosis of pheochromocytoma was confirmed and 644 patients who were determined to not have the tumor. MAIN OUTCOME MEASURES: Test sensitivity and specificity, receiver operating characteristic curves, and positive and negative predictive values at different pretest prevalences using plasma free metanephrines, plasma catecholamines, urinary catecholamines, urinary total and fractionated metanephrines, and urinary vanillylmandelic acid. RESULTS: Sensitivities of plasma free metanephrines (99% [95% confidence interval [CI], 96%-100%]) and urinary fractionated metanephrines (97% [95% CI, 92%-99%]) were higher than those for plasma catecholamines (84% [95% CI, 78%-89%]), urinary catecholamines (86% [95% CI, 80%-91%]), urinary total metanephrines (77% [95% CI, 68%-85%]), and urinary vanillylmandelic acid (64% [95% CI, 55%-71%]). Specificity was highest for urinary vanillylmandelic acid (95% [95% CI, 93%-97%]) and urinary total metanephrines (93% [95% CI, 89%-97%]); intermediate for plasma free metanephrines (89% [95% CI, 87%-92%]), urinary catecholamines (88% [95% CI, 85%-91%]), and plasma catecholamines (81% [95% CI, 78%-84%]); and lowest for urinary fractionated metanephrines (69% [95% CI, 64%-72%]). Sensitivity and specificity values at different upper reference limits were highest for plasma free metanephrines using receiver operating characteristic curves. Combining different tests did not improve the diagnostic yield beyond that of a single test of plasma free metanephrines. CONCLUSION: Plasma free metanephrines provide the best test for excluding or confirming pheochromocytoma and should be the test of first choice for diagnosis of the tumor.

Adolescent↗
PubMed2002

Monoamine metabolism and sympathetic nervous activation following subarachnoid haemorrhage: influence of gender and hydrocephalus.

Subarachnoid haemorrhage is a serious condition, often accompanied by cerebral vasospasm and hydrocephalus, which may result in delayed cerebral ischaemia and neurological deterioration. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system, leading to elevated levels of circulating catecholamines is, at least in part, implicated. In this study, we sought to examine the importance of sympathetic nervous activation and its relation to brain monoaminergic neurotransmission in 25 patients following subarachnoid haemorrhage by examining plasma and cerebrospinal fluid levels of the catecholamines noradrenaline, adrenaline and dopamine, and their metabolites. Total body sympathetic activity was concurrently assessed using isotope dilution methodology. In the early phase following subarachnoid haemorrhage patients exhibited markedly elevated rates of spillover of noradrenaline to plasma (9.11 +/- 1.12 vs. 3.39 +/- 0.26 nmol/min, p < 0.01), with rates being higher in those patients in whom hydrocephalus developed (11.15 +/- 1.40 vs. 7.90 +/- 1.41 nmol/min, p = 0.05). The degree of sympathetic nervous activation tended to be higher in females compared with males. Lower cerebral perfusion pressures were observed in those patients in whom cerebrospinal fluid concentrations of noradrenaline and dopamine metabolites were high. A marked sympathetic nervous activation, more pronounced in women and in those with hydrocephalus, occurs following subarachnoid haemorrhage. The diminished cerebral perfusion seen following subarachnoid bleeding may occur as a result of activation of central catecholaminergic neurones.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2002

Reduced spontaneous baroreceptor sensitivity in patients with renovascular hypertension.

OBJECTIVE: Sympathetic nerve activity is increased in hypertensive patients with renal artery stenosis. Less is known about cardiac vagal function in these patients before and after renal angioplasty. The aim of the present study was to investigate cardiac baroreceptor reflex sensitivity together with total body noradrenaline (NA) spillover in hypertensive patients with renal artery stenosis before, and in some patients, 1 year after renal angioplasty. MATERIAL AND METHODS: Spontaneous baroreceptor reflex sensitivity and total body noradrenaline (NA) spillover were measured in patients with renovascular hypertension before intervention (n = 18), patients being cured/improved 1 year after renal angioplasty (n = 5) and age-matched healthy subjects (n = 25). RESULTS: Hypertensive patients with renal artery stenosis had higher total body NA spillover (4630 +/- 619 versus 3132 +/- 210 pmol/min, P < 0.05) and reduced cardiac baroreceptor reflex sensitivity (6.1 +/- 1.0 versus 10.7 +/- 1.0 ms/mmHg, P < 0.01) compared with healthy subjects. Similar results were obtained (before intervention) in a subgroup of patients (n = 9) with renovascular hypertension defined as cured/improved 1 year following renal angioplasty. Baroreceptor reflex sensitivity improved after renal angioplasty in a subset of patients showing good blood pressure control 1 year after intervention (6.4 +/- 0.7 to 9.4 +/- 1.7 ms/mmHg, P < 0.05). CONCLUSIONS: Patients with renovascular hypertension showed reduced cardiac baroreceptor reflex sensitivity and increased noradrenergic activity, which to some extent was reversed 1 year following successful renal angioplasty.

Angioplasty, Balloon↗