Age-Related Progression of Microvascular Dysfunction in Cystic Fibrosis: New Detection Ways and Clinical Outcomes.

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications.

Cardiac troponin T determination plays a dominant role in diagnosis of myocardial pathologies. Despite generally accepted use of high-sensitive cardiac troponin T assays (hscTnT) and clearly defined cut-off limit in adults, the uncertainty persists in infants. The aim of this study was to assess plasmatic concentrations of hscTnT and describe sequential age-related dynamic changes of hscTnT in healthy infants and toddlers. Seventy-eight children (52 males/26 females) from Czech Republic aged 44 to 872 days (median, interquartile range 271; 126 to 486 days) were consecutively enrolled in the single-center, prospective observational study. Plasma concentrations of hscTnT were analyzed by the electrochemiluminescent method, age-related reference intervals were calculated using the polynominal regression model. Amongst the study population (n=78), the upper limit of hscTnT concentration defined as the 99th percentile was calculated. The 99th percentile with 95 % confidence interval at the end of 2nd, 3rd, 4th, 5th, 6th and 7th month of postnatal life were: 81 (40.6 to 63.6), 61 (36.0 to 55.3), 47 (31.9 to 48.3), 37 (28.1 to 42.3), 30 (24.7 to 37.2) and 25 (21.5 to 32.7) ng/l, respectively. Concentration of adults 99th percentile (14 ng/l) was achieved approximately at 1 year of postnatal life. Statistically significant negative correlation of hscTnT concentration with age (r=-0.81, p<0.001) was found. Significant gender differences were not found (p>0.07). The study revealed substantially increased reference intervals of hscTnT levels in infants when compared with adult population. Based on our preliminary results, the age-related interpretation of hscTnT plasmatic concentration is recommended.

Plethysmographic and biochemical markers in the diagnosis of endothelial dysfunction in pediatric acute lymphoblastic leukemia survivors - new applications.

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.

How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants?

Research and clinical implications on novel cardiac biomarkers has intensified significantly in the past few years. The high-sensitive troponin T (hscTnT) assay plays a dominant role in diagnostic algorithm regarding myocardial injury in adults. Despite generally accepted use of hscTnT there are no data about physiological concentrations and cut-off limits in neonates and infants to date. The aim of this study is to assess hscTnT levels in healthy newborns and infants. Consecutively 454 healthy full termed newborns and 40 healthy infants were enrolled in the study. Samples of cord or venous blood were drawn and tested for hscTnT concentrations with high-sensitive TnT assay (Roche Cobas e602 immunochemical analyzer). The 97.5 percentile of hscTnT concentration was assessed and correlation analysis was performed in neonates. Two hundred and thirteen samples (47 %) were excluded due to blood hemolysis of various degrees in neonates. Finally, the group of 241 healthy newborns was statistically analyzed. The median concentration of hscTnT was 38.2 ng/ml, 97.5 percentile reached 83.0 ng/l (confidential interval 74.1 to 106.9 ng/l). HscTnT concentrations were statistically decreased in hemolytic samples when compared to non-hemolytic samples (34.3 ng/l [26.7 to 42.0 ng/l] and 37.1 ng/l [30.5 to 47.9 ng/l], respectively, p=0.003). Elevated plasma concentrations of hscTnT decreased to adult level within six months. This study has confirmed the higher reference levels of hscTnT in neonates and young infants when compared with adult population. Many extracardiac factors as hemolysis and age may affect the hscTnT level. Based on presented results, a careful clinical interpretation of hscTnT is recommended.

Reduction of renal function during mechanical ventilation of healthy lungs in an animal biomodel.

OBJECTIVES: To identify factors involved in reno-pulmonary interactions during mechanical ventilation. MATERIALS AND METHODS: The study included a total of 25 domestic piglets. The animals were divided into three groups based on different strategies of ventilation. Group A; spontaneously breathing piglets; group B animals ventilated with tidal volume of 6 ml.kg-1 and group C with animals ventilated with tidal volume 10 ml.kg-1. Clinical monitoring and laboratory tests were performed for all groups at baseline and then at 1 hour and 12 hours for groups B and C. Ventilation indices, hemodynamics, urine output, creatinine clearance, glomerular filtration index, fractional excretion of sodium, free water clearance and tissue samples were recorded. The data obtained were statistically analysed. RESULTS: Lower creatinine clearance and renal indices were seen in group B (p < 0.05) and in group C (p < 0.001) at 1 hour, and a difference in urine output for group C (p < 0.01) compared to group A was observed. At 12 hours, there was a further reduction in creatinine clearance and renal indices for group B (p < 0.05) and group C (p < 0.01). The lung mechanics and hemodynamics were not significantly influenced. CONCLUSIONS: The study showed a causal relationship between renal dysfunction and positive pressure mechanical ventilation with respect to tidal volume and time (Tab. 4, Fig. 2, Ref. 17).

Total body response to mechanical ventilation of healthy lungs: an experimental study in piglets.

The objective of our study was to assess the influence of mechanical ventilation on healthy body organs. Fifteen piglets (aged 6 weeks, 19-27 kg) were anesthetized, instrumented, and divided into three groups: Group A - spontaneously breathing, group B - mechanically ventilated with tidal volume 6 ml/kg, and group C - ventilated with tidal volume 10 ml/kg for 12 hours. The parameters of lung, heart, liver and kidney functions neurohumoral regulation and systemic inflammatory reaction were recorded initially (time-1) and after 12 hours (time-12) of mechanical ventilation. At the onset of experiment (time-1) the levels of soluble adhesive molecules were higher (CAM; P<0.01), glomerular filtration index and free water clearance were lower (P<0.05) in both ventilated groups than in group A. Right ventricle myocardial performance index was higher (RIMP; P<0.05) in group C when compared with group A. Levels of CAM (P<0.05) and creatinine clearance (P<0.01) were higher, free water clearance was lower (P<0.05) in group C when compared to group B. At time-12 the RIMP (P<0.05) and levels of CAM were increased (P<0.01), creatinine clearance was decreased (P<0.05) in both ventilated groups compared to the same parameter at time-1. Ventilation index was higher (P<0.05), and hypoxemic index was lower (P<0.01) in group C when compared to group B. In conclusion, this study showed that mechanical ventilation induced changes compatible with early inflammatory response in healthy animals. Higher tidal volumes had detrimental effect on ventilatory parameters, reduced myocardial performance and potentiated adverse reaction of other organs.

Asymmetric dimethylarginine and the effect of folate substitution in children with familial hypercholesterolemia and diabetes mellitus type 1.

A recently discussed cardiovascular risk factor, asymmetric dimethylarginine (ADMA), is known to act as an endogenous inhibitor of endothelial nitric oxide synthase. The aim of this study was to establish 1) the relationship between ADMA and ultrasonographically or biochemically determined endothelial dysfunction in children, and 2) the effect of folate supplementation on these parameters. The study cohort included 32 children with familial hypercholesterolemia (FH), 30 with diabetes mellitus type 1 (DM1) and 30 age-matched healthy children as the control group. Furthermore, twenty-eight randomly selected FH and DM1 children were re-examined after 3-months supplementation with folic acid. Baseline levels of ADMA and oxidized low density lipoproteins (oxLDL) were significantly higher in FH group than in DM1 and healthy children. Children in DM1 group had significantly lower concentration of homocysteine, but ADMA levels were normal. Folic acid supplementation significantly lowered homocysteine and hsCRP levels in both FH and DM1 group; however, ADMA and oxLDL concentrations remained unaltered. In conclusion, ADMA and oxLDL appear to be associated with endothelial dysfunction in children with FH. Administration of folic acid did not influence these markers in both FH and DM1 children.

[Pilot study of the noninvasive assessment of endothelial dysfunction by post-occlusion dopplerometry velocity curves analysis in arteria brachialis]. / Pilotní studie nové moznosti neinvazivního hodnocení dysfunkce endotelu pomocí analýzy charakteru postokluzního prutoku a. brachialis.

BACKGROUND: A new method of noninvasive assessment of endothelial dysfunction was used in this pilot study. Study has been set on a. brachialis dopplerometry velocity curves analysis. Index of blood stream deceleration between the first and second minute of the postocclusion periode was measured on a. brachialis after transient mechanical occlusion of the forearm--so called Deceleration Index. METHODS AND RESULTS: Eighteen patients with so far untreated hypercholesterolemia were involved in our study. Profile of velocity curves became significantly different after six months of fluvastatin therapy, Deceleration Index increased from 3 % to more than 7 % (p<0.05). That correlated with LDL-CH levels decrease, but also with the significant decrease of biochemical markers of endothelial dysfunction (trombomodulin, von Willebrand factor). CONCLUSIONS: The result is corresponding with previously published studies that have proved endothelial function improvement after statin therapy using another ultrasonographic methods.

[Emergency myocardial revascularization during a developing myocardial infarct]. / Urgentní revaskularizace myokardu pri rozvíjejícím se infarktu myokardu.

In 1996-1998 in our Cardiocentre urgent revascularizations were made in 28 patients with developing acute myocardial infarction (AIM) with manifestations of different grades of acute circulatory failure up to developed cardiogenic shock and cardiac arrest. In all patients complete revascularization with a mean number of 2.9 bypasses per patient was made, in one patient at the same time a rupture of the interventricular septum was closed and in two patients an insufficient mitral valve was replaced. From the whole group two patients died during the early postoperative period, two were revised on account of postoperative haemorrhage and two had signs of low cardiac output. Twenty-two patients had a postoperative course without complications. Urgent surgical revascularization in patients developing AIM and circulatory deterioration is the method of primary and definite treatment when primary PTCA is not suitable.