Jane Angel Simonsen

Mechanisms of acute natriuresis in normal humans on low sodium diet

This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin‐angiotensin‐aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day−1) received isotonic saline intravenously (NaLoading: 20 μmol Na+ kg−1 min−1 or ≈11 ml min−1 for 240 min). NaLoading did not change MAP or GFR (by clearance of 51Cr‐EDTA). Significant natriuresis occurred within 1 h (from 9 ± 3 to 13 ± 2 μmol min−1). A 6‐fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related (R= 0.997) as were ANGII and aldosterone (R= 0.999). The slopes were 0.40 pm ANGII (mi.u. renin activity)−1 and 22 pm aldosterone (pm ANGII)−1. Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NOx). In conclusion, sodium excretion may increase 7‐fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP‐ and NOx excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII‐mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.

Normotensive sodium loading in normal man: regulation of renin secretion during β-receptor blockade

Saline administration may change renin-angiotensin-aldosterone system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by beta1-receptors (beta1-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium concentration (Na+ loading; 12 micromol Na+.kg(-1).min(-1) for 4 h). Normal subjects were studied on low-sodium intake with and without beta1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na+ loading decreased plasma renin concentration (PRC) by one-third, plasma ANG II by one-half, and plasma aldosterone by two-thirds (all P < 0.05); surprisingly, these changes were found without, as well as during, acute metoprolol administration. Concomitantly, sodium excretion increased indistinguishably with and without metoprolol (16 +/- 2 to 71 +/- 14 micromol/min; 13 +/- 2 to 55 +/- 13 micromol/min, respectively). Na+ loading did not increase plasma atrial natriuretic peptide, glomerular filtration rate (GFR by 51Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by approximately 2.0 mmHg (P < 0.05). During Na+ loading, sodium excretion increased with CVP at an average slope of 7 micromol.min(-1).mmHg(-1). Concomitantly, plasma vasopressin decreased by 30-40% (P < 0.05). In conclusion, beta1-adrenoceptor blockade affects neither the acute saline-mediated deactivation of RAAS nor the associated natriuretic response, and the RAAS response to modest saline loading seems independent of changes in MAP, CO, GFR, beta1-mediated effects of norepinephrine, and ANP. Unexpectedly, the results do not allow assessment of the relative importance of RAAS-dependent and -independent regulation of renal sodium excretion. The results are compatible with the notion that at constant arterial pressure, a volume receptor elicited reduction in RSNA via receptors other than beta1-adrenoceptors, decreases renal tubular sodium reabsorption proximal to the macula densa leading to increased NaCl concentration at the macula densa, and subsequent inhibition of renin secretion.

Impact of Personal Characteristics and Technical Factors on Quantification of Sodium 18F-Fluoride Uptake in Human Arteries: Prospective Evaluation of Healthy Subjects

Sodium 18F-fluoride (18F-NaF) PET/CT imaging is a promising imaging technique for the assessment of atherosclerosis but is hampered by a lack of validated quantification protocols. Both personal characteristics and technical factors can affect quantification of arterial 18F-NaF uptake. This study investigated whether blood activity, renal function, injected dose, circulating time, and PET/CT system affect quantification of arterial 18F-NaF uptake. Methods: Eighty-nine healthy subjects were prospectively examined by 18F-NaF PET/CT imaging. Arterial 18F-NaF uptake was quantified at the level of the ascending aorta, aortic arch, descending thoracic aorta, and coronary arteries by calculating the maximum 18F-NaF activity (NaFmax), the maximum/mean target-to-background ratio (TBRmax/mean), and the maximum blood-subtracted 18F-NaF activity (bsNaFmax). Multivariable linear regression assessed the effect of personal characteristics and technical factors on quantification of arterial 18F-NaF uptake. Results: NaFmax and TBRmax/mean were dependent on blood activity (β = 0.34 to 0.44, P < 0.001, and β = −0.68 to −0.58, P < 0.001, respectively) and PET/CT system (β = −0.80 to −0.53, P < 0.001, and β = −0.80 to −0.23, P < 0.031, respectively). bsNaFmax depended on PET/CT system (β = −0.91 to −0.57, P < 0.001) but not blood activity. This finding was observed at the level of the ascending aorta, aortic arch, descending thoracic aorta, and the coronary arteries. In addition to blood activity and PET/CT system, injected dose affected quantification of arterial 18F-NaF uptake, whereas renal function and circulating time did not. Conclusion: The prospective evaluation of 89 healthy subjects demonstrated that quantification of arterial 18F-NaF uptake is affected by blood activity, injected dose, and PET/CT system. Therefore, blood activity, injected dose, and PET/CT system should be considered to generate accurate estimates of arterial 18F-NaF uptake.

Cardiac Abnormalities in Adult Patients With Polymyositis or Dermatomyositis as Assessed by Noninvasive Modalities

Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction.

Traditional Cardiovascular Risk Factors and Coronary Artery Calcification in Adults With Polymyositis and Dermatomyositis: A Danish Multicenter Study

To determine the occurrence of traditional cardiovascular (CV) risk factors and coronary artery calcification (CAC) in adults with polymyositis (PM) or dermatomyositis (DM) compared to healthy controls and to assess the association between CV risk factors, PM/DM, and CAC score.

Quantitative myocardial perfusion by O-15-water PET: individualized vs. standardized vascular territories

AIMS Reporting of quantitative myocardial blood flow (MBF) is typically performed in standard coronary territories. However, coronary anatomy and myocardial vascular territories vary among individuals, and a coronary artery may erroneously be deemed stenosed or not if territorial demarcation is incorrect. So far, the diagnostic consequences of calculating individually vs. standardly assessed MBF values have not been reported. We examined whether individual reassignment of vascular territories would improve the diagnostic accuracy of MBF with regard to the detection of significant coronary artery disease (CAD). METHODS AND RESULTS Forty-four patients with suspected CAD were included prospectively and underwent coronary CT-angiography and quantitative MBF assessment with O-15-water PET followed by invasive, quantitative coronary angiography, which served as reference. MBF was calculated in the vascular territories during adenosine stress according to a standardized 17-segment American Heart Association model and an individualized model, using CT-angiography to adjust the coronary territories to their feeding vessels. Individually defined territories deviated from standard territories in 52% of patients. However, MBF in the three coronary territories defined by standard and individualized models did not differ significantly, except in one patient, in whom the MBF of an individualized coronary territory deviated sufficiently as to change the test from a false positive to a true negative result in this particular territory. CONCLUSION Disparity between standardized and individualized vascular territories was present in half of the patients, but had little clinical impact. Still, caution should be taken not always to rely on standard territories, as this may at times cause misinterpretation.

Outcome with invasive versus medical treatment of stable coronary artery disease: influence of perfusion defect size, ischaemia, and ejection fraction

AIMS Our aim was to address the combined influence of myocardial perfusion defects and left ventricular ejection fraction (LVEF) on outcome with coronary revascularisation in stable CAD patients. METHODS AND RESULTS Of 527 patients with ischaemia by myocardial perfusion scintigraphy, 343 had medical therapy (Med) and 184 revascularisation (Revasc). During 5.3 years of follow-up, there was no intergroup difference in rates of death/myocardial infarction. Propensity score adjustment demonstrated a benefit of Revasc over Med with large defects (>14% of the myocardium), marked ischaemia (>10% of the myocardium), or LVEF <50%. However, defect size, ischaemia, and LVEF were correlated. In multivariate models, the Med versus Revasc hazard ratio (HR) was 4.06 times larger for LVEF <50% than for LVEF ≥50% (p=0.04) and 3.01 times larger for marked compared to mild/moderate ischaemia (p=0.11), whereas the effect of large compared to small/moderate defects vanished when adjusted for LVEF and ischaemia (HR=1.01, p=0.99). Considering the outcome difference as a function of both LVEF and ischaemia, we found no advantage or even a disadvantage of revascularisation in patients with mild/moderate ischaemia and preserved LVEF. CONCLUSIONS A benefit of revascularisation was found only in case of marked ischaemia or LVEF <50%. For treatment triage, both perfusion parameters and LVEF should be considered.

Systemic nitric oxide clamping in normal humans guided by total peripheral resistance

Aim:  We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels.

Tc-99m-Human Serum Albumin Transit Time as a Measure of Arm Breast Cancer-Related Lymphedema

Background: Lymphoscintigraphy has often been used for evaluating arm lymphatic dysfunction, but no optimal approach for quantification has so far emerged. We propose a quantifiable measure of lymphatic function that we applied in patients treated for breast cancer. Methods: Eleven patients, aged 34–68 years, with unilateral arm lymphedema following breast cancer treatment underwent bilateral lymphoscintigraphy using intradermal injection in both hands of technetium-99m–labeled human serum albumin and sequential 5 min imaging for 5 hours. The mean transit time (MTT) in the arms was calculated based on time activity curves generated from injection site and arm regions. Visual lymphedema scoring was performed based on dermal backflow and lymph node presence. Excess arm volume was calculated from circumference measurements. Results: The MTT (mean ± SD) was significantly longer in the lymphedema arm than in the normal arm: 60.1 ± 27.7 versus 5.4 ± 2.5 minutes (mean difference, 54.7 minutes; 95% confidence interval, 36.5–72.9 minutes; P < 0.0001). Patients with previous erysipelas infection had significantly longer MTT than other patients (mean difference, 43.7 minutes; 95% confidence interval, 18.6–68.7 minutes; P < 0.001). There was a positive correlation between MTT and excess arm volume (r = 0.64; P = 0.04) and number of lymph nodes removed (r = 0.65; P = 0.03) but no correlation between visual score and MTT. Conclusion: Measurements of MTT were able to discriminate lymphedema from healthy arm and MTT correlated with relevant markers for lymphedema severity. We encourage further research using the MTT approach for monitoring lymphedema and evaluation of treatment response.

111 Indium-transferrin for localization and quantification of gastrointestinal protein loss

Objective. To evaluate the indium-111 (111In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss. Methods. Fourteen patients and 15 healthy subjects underwent an 111In-transferrin study consisting of abdominal scintigraphy, whole-body counting measurement and determination of plasma activity of 111In during the course of 5 days. Two of the patients went through a subsequent chromium-51–trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods. Results. The patients had a mean±SEM whole-body loss of 111In of 10.9±2.9% for 96 h, while the healthy controls lost 1.8±1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0±1.0 h in patients and 12.1±1.5 h in controls (p=0.0007). Scintigraphically, patients had obvious abdominal foci of activity, while the control subjects showed diffuse activity. Anatomic localization of the leaking spot seemed more uncertain. By comparison with the 51Cr trichloride test, the loss of radio-labelled protein appeared to be in the same order of magnitude. Conclusions. Quantification of gastrointestinal protein loss can be done without collecting faeces. Normal subjects have a loss of a few per cent, making the 111In-transferrin method comparable with the former standard using 51CrCl3–trichloride. Plasma measurements of 111In are not predictive of the magnitude of the loss. Scintigraphic localization of the site of the loss needs to be optimized, for instance by serial imaging or image fusion with an anatomical modality.