In-vitro antiplatelet effect of melatonin in healthy individuals and patients with type 2 diabetes mellitus.

PURPOSE: The incidence of acute myocardial infarctions (AMI) shows circadian variation typically peaking during morning hours with a decline at night. However, this variation does not occur in patients with diabetes mellitus (DM). The night's decline of AMI may be partially explained by melatonin-related platelet inhibition. Whether this effect is absent in diabetic patients is unknown. The aim was to study the effect of melatonin on in-vitro platelet aggregation in healthy individuals and patients with type 2 DM. METHODS: Platelet aggregation was measured in blood samples from healthy individuals (n = 15) and type 2 DM patients (n = 15) using multiple electrode aggregometry. Adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin (TRAP) were used as agonists. Aggregability for each subject was tested after adding melatonin in two concentrations. RESULTS: In healthy individuals, melatonin inhibited platelet aggregation in both higher (10-5 M) and lower concentrations (10-9 M) induced by ADP, ASPI, and TRAP (p < 0.001, p = 0.002, p = 0.029, respectively). In DM patients, melatonin did not affect platelet aggregation in both concentrations induced by ADP, ASPI, and TRAP. Melatonin decreased platelet aggregation induced by ADP, ASPI, and TRAP significantly more in healthy individuals compared to patients with DM. (p = 0.005, p = 0.045 and p = 0.048, respectively). CONCLUSION: Platelet aggregation was inhibited by melatonin in healthy individuals. In-vitro antiplatelet effect of melatonin in type 2 DM patients is significantly attenuated.

Preoperative NT-proBNP values in patients with atrioventricular septal defect and its role as a predictor of early postoperative course.

OBJECTIVES: Atrioventricular septal (AVSDC) defect presents by excessive pulmonary blood flow and congestive heart failure in children. This study was designed to identify and compare N-terminal pro-brain natriuretic peptide (NT-proBNP) values in complete and incomplete form at the time of surgery, and evaluation of postoperative course. METHODS: The prospective study included thirty-one patients with complete and fifteen with intermediate forms, undergoing surgery in the period from May 2009 to January 2014. Pre- and post-operative variables were statistically analyzed. RESULTS: The median value of NT-proBNP was 1420.0 pg/mL, with elevated levels in complete form (1656.0 vs 488.0 pg/mL, p < 0.001); age and weight with negative correlation. Other preoperative variables (genetic disorder, atrioventricular valve regurgitation, borderline ventricle) were not significant. Higher incidence of postoperative variables was present in complete form, namely mechanical ventilation (p < 0.03), dose and length of vasopressors (p < 0.002), ICU stay (p < 0.04), and complications (p < 0.05). NT-proBNP analysis as a predictor of postoperative course showed an association with longer ventilatory (> 48 hours) and inotropic forms of support, ICU stay, and presence of infection. CONCLUSION: NT-proBNP value might be helpful in the decision-making process of early surgical treatment of complete form of AVSDC, and useful as a predictor of early post-operative course (Tab. 4, Fig. 3, Ref. 14).

[Natriuretic peptides in patients with aortic stenosis]. / Nátriuretické peptidy pri aortovej stenóze.

INTRODUCTION: The aim of this research was to, in patients with severe (tight) aortic stenosis (AoS), evaluate a) an association between clinical and some haemodynamic characteristics and natriuretic peptides (ANP, BNP) concentrations and b) usefulness of these hormones in the decision making on the next therapeutic steps. METHODS: Echocardiography and 6-minut exertion walking test were performed in 23 consecutive patients (12 men, 11 women; age 67 +/- 7 years) and 20 controls together with ANP and BNP measurements from three plasma samples before, immediately after and 20 minutes after the exertion test. RESULTS: There was high inter-individual variability in the ANP and BNP concentrations in patients with AoS. All ANP and BNP were significantly higher than in the controls (ANP 1, 2, 3, p < 0.001; BNP 1, 2, 3, p < 0.001). Only the ANP levels increased significantly after the exercise (ANP 1 vs. ANP 2 = 0.011; ANP 2 vs. ANP 3 p = 0.037). We identified significant correlations between aortic peak gradient and BNP 1, 2 (r = 0.821, p < 0.001) and ANP 1, with BNP correlations being stronger. We did not find any correlations with aortic valve area and the left ventricle mass. The hormone levels were non-significantly increased depending on NYHA classification. Exercise did not improve validity ofANP and BNP measurement. Their values had high sensitivity but low specificity in detecting critical AoS. CONCLUSION: ANP and mainly BNP helped to exclude severe AoS but they were not useful in detecting lower, orderline gradients. We did not prove ANP and BNP to be significant factors in decision making about the timing of AoS surgery.

Long-term cardiac effects of treatment for childhood leukemia.

Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Biochemical correlates of minimal myocardial changes can be analyzed using a commercially available rapid assay. Biomarkers are considered more sensitive markers of subclinical cardiotoxicity than conventional electrocardiographic and echocardiographic methods. The aim of this study was to determine the values of plasma N-terminal pro brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T (cTnT) in asymptomatic childhood leukemia survivors after anthracycline therapy in comparison with healthy volunteers. The survivors also underwent a detailed echocardiography. Twenty six survivors of leukemia previously treated with anthracyclines with total cumulative dose 95-600 (median 221) mg/m(2) were evaluated. Analyses of cTnT and NT-proBNP from blood samples and echocardiography were performed 5-25 years after completion of therapy for childhood leukemia. Control group for biochemical analyses consisted of 22 age- and gender- matched apparently healthy volunteers. Values of NT-proBNP were significantly elevated in ANT group compared to controls (35.1 +/- 37.8 vs. 9.6 +/- 6.7 pg/ml, P<0.010). CTnT remained below the diagnostic cut-off values in both groups. All echocardiographic parameters of patients remained normal. In conclusion, differences in NT-proBNP values between patients treated with anthracyclines and healthy volunteers might signal an initial stage of anthracycline-induced myocardial damage. The potential of this biomarker to detect subclinical anthracycline-induced myocardial alterations before development of echocardiographic and clinical changes is promising.

Natriuretic peptides: biochemical markers of anthracycline cardiac toxicity?

Patients with cancer are often treated with potentially cardiotoxic chemotherapeutics. Cardiotoxicity ranges from relatively benign arrhythmias to serious conditions such as myocardial ischemia/infarction, congestive heart failure, and cardiomyopathy. In spite of different diagnostic methods, with echocardiography as a gold standard, there is an intensive search for new diagnostic tools for the early detection of myocardial abnormalities. Available data suggest that the levels of circulating cardiomarkers can monitor the extent and severity of the myocardial damage. The role of routinely used cardiomarkers is controversial and limited in this setting. Natriuretic peptides have shown promising results in assessment and monitoring of both acute and late clinical and subclinical damage of the myocardium in association with chemotherapy. This article reviews clinical studies evaluating the role of natriuretic peptides in the early diagnosis of anthracycline cardiotoxicity, and their use in the management of cancer survivors.

Natriuretic peptides and endothelin-1 in patients undergoing coronary artery bypass grafting.

Off-pump coronary artery bypass grafting (CABG) is an alternative to conventional CABG using cardiopulmonary bypass. Off-pump technique reduces the complications of CABG performed with extracorporeal circulatory assistance (Lancey et al. 2000; Mack et al. 2004a,b). The object of this study was to compare peri- and postoperative time courses of vasoactive peptides - atrial natriuretic poptide (ANP), brain natriuretic poptide (BNP) and endothelin-1 (ET-1) in off-pump versus on-pump CABG. 22 patients, who underwent on-pump (group A, n = 11) or off-pump CABG (group B, n = 11) were studied. The peri- and postoperative time courses of plasma ANP and BNP were similar in both groups. A statistically significant difference between ET-1 plasma level 2 h after surgery in the group A and ET-1 plasma level 2 h after surgery in the group B (2.46 + or - 1.14 pg/ml/Ht versus 0.74 + or - 0.09 pg/ml/Ht, p < 0.0001) was found. Different CABG techniques were not associated with significant changes in peri- and postoperative plasma ANP and BNP. By contrast, plasma ET-1 significantly rose in the group A 2 h after surgery, indicating endothelial damage.

Antioxidant status of patients after on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: It has been convincingly established that cardiopulmonary bypass routinely used in cardiac surgery induces an oxidative stress. The extensive production of reactive oxygen species occurring during cardiopulmonary bypass has a deleterious effect on the endogenous antioxidant defense pool. The recovery of antioxidant enzyme activities as well as other antioxidatively substances is one of the important tasks for the effective defense of patients in the postoperative period. AIM OF THE STUDY: Oxidative stress markers and the antioxidant status and the activities of some antioxidant enzymes were studied in patients during one-week period after cardiac revascularization performed using cardiopulmonary bypass and the results were compared with patients operated by off-pump technique. PATIENTS AND METHODS: Thirty-nine patients undergoing elective surgical revascularization (coronary artery bypass grafting) were divided in two groups: twenty-two patients operated using cardiopulmonary bypass (group A) and a group B of seventeen patients undergoing pump-off surgery. Blood samples were drawn before operation and then in course of the first week after surgery. The following biochemical parameters were estimated: plasma levels of total antioxidant status (TAS) and of thiobarbituric acid reactive substances (TBARS) as well as erythrocyte activities of two antioxidant enzymes--superoxide dismutase (SOD) and glutathione peroxidase (GPx). RESULTS: There was a significantly decreased preoperative and also postoperative levels of TAS associated with a preoperatively increased level of TBARS in group A only. In both groups of patients (especially in group B), markedly decreased activity of SOD was observed. The increase of GPx activity--especially on the third postoperative day--was not significant. CONCLUSIONS: Regardless of the surgical technique, both groups of patients had a markedly decreased antioxidant capacity with a significantly increased production of lipid peroxides especially in patients operated with cardiopulmonary bypass. The decreased antioxidant status was connected with decreased erythrocyte activity of SOD. Therefore, we recommend the regular supply of antioxidant acting substances (antioxidant vitamins and coenzyme Q10) be included in their standard therapeutic strategy especially in the preoperative period. (Tab. 2, Fig. 4, Ref: 22.)

Cytokine levels in patients with a very low left ventricular ejection fraction after open heart surgery.

INTRODUCTION: Cardiopulmonary bypass and cardiac operations are obligatorily connected with systemic inflammatory reaction. Production of proinflammatory cytokines is responsible also for negative effects on the myocardial function. OBJECTIVE OF STUDY: Follow-up of the dynamic changes of proinflammatory and antiinflammatory cytokine levels in patients with left ventricular dysfunction during the first week after cardiac surgery. PATIENTS AND METHODS: A total of nine patients with a very low left ventricular ejection fraction (22.75 +/- 0.65%) who had undergone cardiac surgery (for coronary artery bypass grafting or aortic valve reconstruction) were investigated during the first after week operation. The preoperative and postoperative plasma levels of tumor necrosis factor (TNF), interleukin-8 (IL-8) and interleukin-10 (IL-10) were estimated by means of ELISA technique. RESULTS: With respect to the preoperative levels, on the first postoperative day the levels IL-8 (from 9.36 to 16.65 pg/ml) (p < 0.05) and of IL-10 (from 6.93 to 28.09 pg/ml) (p < 0.02) significantly rose with a stepwise decrease down to the seventh day after surgery. From the third to seventh day an insignificant increase in TNF level was also noted. CONCLUSIONS: The results have shown that open heart surgery in patients with a severe left ventricular dysfunction evoked a systemic inflammatory response demonstrated by early increase in proinflammatory cytokine IL-8 and was accompanied by increased level of antiinflammatory cytokine IL-10. Despite stepwise decrease in IL-8 levels, they did not reach the preoperative levels, not even on the seventh postoperative day. (Tab. 1, Fig. 3, Ref. 21.)

[Biochemical markers of perioperative myocardial infarct in non-cardiac surgery]. / Biochemické markery perioperacného infarktu myokardu v nesrdcovej chirurgii.

Perioperative myocardial infarction as well as other major cardiac events induced by myocardial ischemia during and after a more complex or long-lasting operation represents a permanent threat for a successful outcome. High number of cardiac ischemic events especially following major vascular surgery and in elder subjects requires early, sensitive and specific diagnostic markers. This review paper presents conventional as well as novel biochemical methods fulfilling the above mentioned criteria. Until now used estimations of traditional enzyme activities (aspartate aminotransferase and lactate dehydrogenase) are either entirely discarded or subsequently lose their importance (i.e. activities of total creatine kinase and its MB-isoenzyme) an instead modern methods that estimate the amounts of specific cardiac proteins--troponins T and I, constituents of myocardial contractile apparatus--released from ischemized heart are used. Patient's monitoring by means of these cardiac markers allows an early, rapid and reliable estimation of perioperative myocardial infarction enabling possible to arrange an immediate effective treatment. Recently the myocardial regulatory protein troponin I is considered the most specific cardiac marker the plasma level of which does not increase in acute damage and chronic diseases of skeletal muscles, nor in chronic renal failure. (Ref. 52.)

Carnitine level and several lipid parameters in venous blood of newborns, cord blood and maternal blood and milk.

To obtain a rather complex picture on fat metabolism in newborns, fundamental characteristics of this metabolism as well as the carnitine level in their blood was correlated with corresponding values from cord blood, maternal blood and milk. The concentrations of cholesterol (CHOL), triglycerides (TGL) and apolipoprotein B (Apo-B) in 4 days old infants were higher than in cord blood (P < 0.01 and P < 0.001, resp.), but were only 50% of those in blood of the respective mothers. No differences in HDL-CHOL were observed, whereas the level of apolipoprotein A (Apo-A) in cord blood exceeded that in newborn blood (P < 0.05). The level of carnitine in milk was about twice as high as in maternal blood (P < 0.001) which was the consequence of the high acylcarnitine content in milk. Our results represent a basis for comparison of normal and pathologically altered metabolic situation, e.g. in hypotrophic newborns and potentially in newborns in need of parenteral nutrition.