ABSTRACT
Congestive heart failure is accompanied by increased cardiac brain natriuretic peptide (BNP) gene expression with elevated plasma concentrations of BNP and its precursor, proBNP. We ...investigated if myocardial ischemia in the absence of overt heart failure may be another mechanism for increased myocardial BNP expression. The BNP expression was examined in hypoxic myocardium of patients undergoing coronary bypass grafting surgery, in patients with coronary artery disease and normal left ventricular function undergoing percutaneous transluminal intervention therapy, and in heart failure patients without coronary artery disease. BNP mRNA was quantified by real‐time PCR, and plasma BNP and proBNP concentrations were measured with radioimmunoassays. Quantitative analysis of BNP mRNA in atrial and ventricular biopsies from coronary bypass grafting patients revealed close associations of plasma BNP and proBNP concentrations to ventricular, but not atrial, BNP mRNA levels. Plasma BNP and proBNP concentrations were markedly increased in patients with coronary artery disease but without concomitant left ventricular dysfunction. These results are compatible with the notion that myocardial ischemia, even in the absence of left ventricular dysfunction, augments cardiac BNP gene expression and increases plasma BNP and proBNP concentrations. Thus, elevated BNP and proBNP concentrations do not necessarily reflect heart failure but may also result from cardiac ischemia.
To explore the putative associations of plasma copeptin, the C-terminal portion of provasopressin and a surrogate marker for arginine vasopressin secretion, with obesity-related health problems, such ...as hyperlipidaemia, hyperinsulinaemia, hyperglycaemia, high blood pressure and an android fat distribution.
In 103 obese men (mean age ± standard deviation: 49.4 ± 10.2 years) and 27 normal weight control men (mean age: 51.5 ± 8.4 years), taking no medication, we measured 24-h ambulatory blood pressure, fasting blood concentrations of copeptin, lipids, glucose and insulin, and determined body composition by dual energy X-ray absorptiometry scanning.
The obese men had higher median (interquartile range) plasma copeptin concentrations 6.6 (4.6-9.5) vs. 4.9 (3.5-6.8) pmol/l, P = 0.040 compared with the normal weight men. In the obese men, plasma copeptin was not related to 24-h systolic blood pressure (r = 0.11, P = 0.29), 24-h diastolic blood pressure (r = 0.11, P = 0.28), BMI (r = 0.09, P = 0.37), total body fatness percentage (r = 0.10, P = 0.33), android fat mass percentage (r = 0.04, P = 0.66) or serum triglyceride concentrations (r = 0.04; P = 0.68). In contrast, plasma copeptin was associated with higher serum insulin concentrations (r = 0.26, P = 0.0085) and insulin resistance as assessed by the homeostasis assessment model (r = 0.28, P = 0.0051).
Plasma copeptin, a surrogate marker for arginine vasopressin secretion, is higher in obese men compared with normal weight men, and is associated with abnormalities in glucose and insulin metabolism, but not with higher blood pressure or an android fat distribution in obese men.
It is well established that cardiac failure increases cardiac B‐type natriuretic peptide (BNP) expression due to myocardial stretching. However, patients with ischemic heart disease also display ...increased plasma BNP and proBNP concentrations despite preserved cardiac function. In this study, we examined whether acute myocardial hypoxia increases cardiac BNP expression. Surgical reduction of the blood flow to an area of the anterior ventricular wall in pigs reduced the myocardial oxygen tension from 46 ± 4 to 13 ± 5 mmHg. The tissue contents of VEGF and BNP mRNA increased 1.8‐fold and 3.5‐fold, respectively (n=10, P<0.005) in hypoxic compared with normoxic ventricular myocardium after 2.2 ± 0.2 h; the magnitude of the increase in BNP mRNA expression was positively correlated with that of VEGF in hypoxic myocardium (r=0.66, P<0.05). In support of a hypoxia‐induced increase of BNP gene transcription, the content of a premature BNP mRNA was increased in hypoxic myocardium (4.8‐fold, P<0.005) and in freshly harvested ventricular myocytes when kept in culture flasks and oxygen‐deprived for 3 h (2.2‐ fold, P=0.002). ProBNP peptide accumulated in the medium of freshly harvested ventricular myocyte cultures but was undetectable in ventricular myocardium, indicating rapid release of the newly synthesized proBNP peptide. Accordingly, the plasma proBNP concentration increased after 2 h of myocardial hypoxia (P=0.028). Cumulatively, the data suggest that acute hypoxia stimulates cardiac BNP expression.
A specially designed heating system for temperature-programmed HPLC was developed based on experimental measurements of eluent temperature inside a stainless steel capillary using a very thin ...thermocouple. The heating system can be operated at temperatures up to 225
°C and consists of a preheating, a column heating and a cooling unit. Fast cycle times after a temperature gradient can be realized by an internal silicone oil bath which cools down the preheating and column heating unit. Long-term thermal stability of a polybutadiene-coated zirconium dioxide column has been evaluated using a tubular oven in which the column was placed. The packing material was stable after 50
h of operation at 185
°C. A mixture containing four steroids was separated at ambient conditions using a mobile phase of 25% acetonitrile:75% deionized water and a mobile phase of pure deionized water at 185
°C using the specially designed heating system and the PBD column. Analysis time could be drastically reduced from 17
min at ambient conditions and a flow rate of 1
mL/min to only 1.2
min at 185
°C and a flow rate of 5
mL/min. At these extreme conditions, no thermal mismatch was observed and peaks were not distorted, thus underlining the performance of the developed heating system. Temperature programming was performed by separating cytostatic and antibiotic drugs with a temperature gradient using only water as the mobile phase. In contrast to an isocratic elution of this mixture at room temperature, overall analysis time could be reduced two-fold from 20 to 10
min.
Objectives
YKL‐40 is an inflammatory biomarker associated with disease activity and mortality in patients with diseases characterized by inflammation and tissue remodelling. The aim of this study was ...to describe the prognostic value of YKL‐40 in an unselected patient population.
Design
In consecutive patients admitted to hospital during a 1‐year period, blood was collected and information regarding final diagnosis and mortality was collected. Median follow‐up time was 11.5 years.
Setting
District hospital, Copenhagen, Denmark.
Patients
A total of 1407 patients >40 years of age were admitted acutely.
Main outcome measure
All‐cause mortality.
Results
Median YKL‐40 was increased in patients (157 μg L−1, range 13–7704 μg L−1) compared to healthy controls (40 μg L−1, range 29–58 μg L−1; P < 0.001). Patients with YKL‐40 in the highest quartile had a hazard ratio (HR) of 7.1 95% confidence interval (CI) 4.2–12.0 for all‐cause mortality in the first year and 3.4 (95% CI 2.8–4.2) in the total study period, compared to those in the lowest quartile (HR = 1). The HR for death for all patients with YKL‐40 above the normal age‐corrected 95th percentile was 2.1 (95% CI 1.6–2.7) after 1 year and 1.5 (95% CI 1.3–1.7) during the total study period, compared to patients with YKL‐40 below the age‐corrected 95th percentile. The results of multivariable analysis showed that YKL‐40 was an independent biomarker of mortality; this was most significant in the first year. YKL‐40 was a marker of prognosis in all disease categories. The HR for death was increased in patients with YKL‐40 above the normal age‐corrected 95th percentile in healthy subjects independent of type of disease (all P < 0.001).
Conclusion
The level of YKL‐40 at admission is a strong predictor of overall mortality, independent of diagnosis and could be useful as a biomarker in the acute evaluation of all patients.
Background Increased plasma concentrations of cardiac‐derived B‐type natriuretic peptide (BNP) and N‐terminal pro‐B‐type natriuretic peptide (proBNP) are both associated with left ventricular ...dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We therefore examined the renal and peripheral extraction of N‐terminal proBNP and BNP.
Materials and methods The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N‐terminal proBNP and BNP.
Results Neither the peripheral N‐terminal proBNP (13, 11, 19 pmol L−1, NS) nor the BNP plasma concentrations (4, 12, 9 pmol L−1, NS) differed between the patient groups. In addition, similar renal extractions were observed in the groups. The renal extraction of N‐terminal proBNP (0·16) was not different from that of BNP (0·16). In contrast, the N‐terminal proBNP extraction in the lower extremity was markedly lower compared with BNP (0·00 vs. 0·125, P = 0·007).
Conclusions A comparable renal elimination of N‐terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may explain the higher N‐terminal proBNP compared with BNP concentrations in normal plasma.
Free diving is associated with extreme hypoxia. This study evaluated the combined effect of maximal static breath holding and underwater swimming on plasma biomarkers of tissue hypoxemia: ...erythropoietin, neuron‐specific enolase and S100B, C‐reactive protein, pro‐atrial natriuretic peptide, and troponin T. Venous blood samples were obtained from 17 competing free divers before and 3 h after sessions of static apnea and underwater swimming. The heart was evaluated by echocardiography. Static apnea for 293 ± 78 s (mean ± SD) and subsequent 88 ± 21 m underwater swimming increased plasma erythropoietin from 10.6 ± 3.4 to 12.4 ± 4.1 mIU/L (P = 0.013) and neuron‐specific enolase from 14.5 ± 5.3 to 24.6 ± 6.4 ng/mL (P = 0.017); C‐reactive protein decreased from 0.84 ± 1.0 to 0.71 ± 0.67 mmol/L (P = 0.013). In contrast, plasma concentrations of S100B (P = 0.394), pro‐atrial natriuretic peptide (P = 0.549), and troponin T (P = 0.125) remained unchanged and, as assessed by echocardiography, the heart was not affected. In competitive free divers, bouts of static and dynamic apnea increase plasma erythropoietin and neuron‐specific enolase, suggesting that renal and neural tissue, rather than the heart, is affected by the hypoxia developed during apnea and underwater swimming.
Background
Cholesterol is essential for cell membrane stability, permeability, and fluidity. Cholesterol is present in seminal plasma, but whether a relationship between the level of cholesterol in ...seminal plasma and semen quality exists remains to be elucidated.
Objectives
To explore the association between cholesterol levels in seminal plasma and serum cholesterols, semen quality, and serum reproductive hormones. Secondly, to explore whether the associations are biologically plausible.
Materials and Methods
An association study between cholesterol levels in seminal plasma and semen quality in 403 men, median age 19 years, from the general population. Additionally, an immunohistochemical evaluation of proteins involved in cholesterol metabolism and transport in tissues from the male reproductive tract (testis, epididymis, prostate, and seminal vesicle). Tissue specimens were investigated by immunohistochemistry for markers of cholesterol metabolism and transport (ABCA1, ABCG1, CYP11A1, CYP51A1, HMGCR, LAL, LCAT, LDLR, and SOAT1).
Results
Trend analyses showed that total amount of total cholesterol in seminal plasma was positively associated with sperm concentration, total sperm count, sperm motility, and morphology (all p < 0.008, adjusted). Cholesterol concentrations in seminal plasma were neither associated with serum cholesterol and lipid levels nor serum reproductive hormone (FSH, LH, testosterone, estradiol, sex‐hormone‐binding globulin, inhibin b) levels. All investigated markers of cholesterol metabolism and transport were expressed in the investigated tissue specimens to varying degrees.
Discussion
Seminal plasma level of cholesterol was positively associated with semen parameters. The presence of proteins and enzymes involved in cholesterol metabolism in Leydig cells, Sertoli cells, and maturing germ cells in the seminiferous tubules supports the view that cholesterol may be important for spermatogenesis.
Conclusion
Cholesterol level in seminal plasma may be an indicator of semen quality. Investigations are needed to corroborate or refute our findings and to clarify the exact role of cholesterols for semen quality.
Background:
During abdominal surgery, traction of the mesenterium provokes mesenteric traction syndrome, including hypotension, tachycardia, and flushing, along with an increase in plasma ...prostacyclin (PGI2). We evaluated whether postoperative complications are related to mesenteric traction syndrome during esophagectomy.
Methods:
Flushing, hemodynamic variables, and plasma 6-keto-PGF1α were recorded during the abdominal part of open (n = 25) and robotically assisted (n = 25) esophagectomy. Postoperative complications were also registered, according to the Clavien-Dindo classification.
Results:
Flushing appeared in 17 (open) and 5 (robotically assisted) surgical cases (p = 0.001). Mean arterial pressure was stable during both types of surgeries, but infusion of vasopressors during the first hour of open surgery was related to development of widespread (Grade II) flushing (p = 0.036). For patients who developed flushing, heart rate and plasma 6-keto-PGF1α also increased (p = 0.001 and p < 0.001, respectively). Furthermore, severe postoperative complications were related to Grade II flushing (p = 0.037).
Conclusion:
Mesenteric traction syndrome manifests more frequently during open than robotically assisted esophagectomy, and postoperative complications appear to be associated with severe mesenteric traction syndrome.
Both impaired left ventricular (LV) global longitudinal strain (GLS) and increased plasma concentrations of natriuretic peptides(NP) are associated with a poor outcome in heart failure (HF). ...Increased levels of NP reflect increased wall stress of the LV. However, little is known about the relationship between LV GLS and NP. This aim of this study was to evaluate the relationship between the echocardiographic measure LV GLS and plasma levels of NP.
We prospectively included 149 patients with verified systolic HF at the baseline visit in an outpatient HF clinic. LV GLS was assessed by two dimension speckle tracking and plasma concentrations of N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) and pro-atrial-natriuretic-peptide (proANP) were analysed.
The patients had a median age of 70 years, 28.2 % were females, 26.5 % were in functional class III-IV, median left ventricular ejection fraction (LVEF) was 33 % and median LV GLS was -11 %. LV GLS was associated with increased plasma concentrations of NT-proBNP and proANP in multivariate logistic regression (NT-proBNP: Odds RatioGLS: 7.25, 95 %-CI: 2.48-21.1, P < 0.001 and proANP: Odds RatioGLS: 3.26, 95-%-CI: 1.28-8.30, P = 0.013) and linear regression (NT-proBNP: βGLS: 1.19, 95 %-CI: 0.62-1.76, P < 0.001 and proANP: βGLS: 0.42, 95-%-CI: 0.11-0.72, P = 0.007) models after adjustment for traditional confounders (age, gender, body-mass-index, atrial fibrillation, renal function) and left atrial volume index.
Impaired LV GLS is associated with increased plasma concentrations of NP and our data suggest that left ventricular myocardial mechanics estimated by LV GLS reflects myocardial wall stress in chronic systolic HF.
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