PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study.

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.

[Asymmetric dimethylarginine: predictor of cardiovascular diseases?]. / Aszimmetrikus dimetilarginin: a cardiovascularis betegségek prediktora?

Cardiovascular diseases are the most common diseases worldwide. They are responsible for one third of global deaths and they are the leading cause of disability, too. The usage of different levels of prevention in combination with effective risk assessment improved these statistical data. Risk assessment based on classic risk factors has recently been supported with several new markers, such as asymmetric dimethylarginine, which is an endogenous competitive inhibitor of nitric oxide synthase. Elevated levels of asymmetric dimethylarginine have been reported in obese, smoker, hypercholesterolemic, hypertensive and diabetic patients. According to previous studies, asymmetric dimethylarginine is a suitable indicator of endothelial dysfunction, which is held to be the preceding condition before atherosclerosis. Several researches found positive correlation between higher levels of asymmetric dimethylarginine and coronary artery disease onset, or progression of existing coronary disease. According to a study involving 3000 patients, asymmetric dimethylarginine is an independent risk factor of cardiovascular mortality in patients with coronary artery disease. This article summarizes the role of asymmetric dimethylarginine in prediction of cardiovascular diseases, and underlines its importance in cardiovascular prevention.

The effect of physical exercise on arterial stiffness parameters in young sportsmen.

OBJECTIVE: This study aimed to determine the effect of single-bout exercise on aortic stiffness parameters in young basketball players. METHOD AND RESULTS: A total of 108 young male subjects (mean age 14.2 ± 3.4 years) were enrolled into the study. Simultaneous measure- ment of aortic pulse wave velocity (PWVao) and augmentation index (Alxao) were performed with the oscillometric, occlusive device. Echocardiographic parameters of left ventricular systolic and diastolic function at rest were also measured in sportsmen. We did not find significant differences of resting PWVao in comparison with young sportsmen (S) and age-matched healthy volunteers (V): 5.82 ± 0.14 m/s vs 5.83 ± 0.12 m/s for S and V groups, respectively. The values of PWVao measured after dynamic exercise, isometric exercise, and rest were 8.0 ± 0.5 m/s, 5.86 ± 0.1 m/s and 5.82 ± 0.1 m/s, respectively. We confirmed that values after dynamic exercise are significantly different from those after isometric exercise (P < 0.01) and those after rest (P < 0.01). The Alxao values exhibited a considerable, but statistically non-significant, decrease during dynamic exercise in the three groups (11.7 ± 7% vs 3.8 ± 3% vs- 0.9 ± 0.9% for groups 1, 2, and 3, respectively). CONCLUSION: We applied a feasible, clinically useful method which allowed us to measure changes in aortic PWV and Alx during acute, single-bout exercise on the basketball court in young sportsmen.

Simple and choice reaction times are prolonged following extracorporeal circulation: a potential method for the assessment of acute neurocognitive deficit.

BACKGROUND: Cognitive deficit related to open heart surgery came into the focus of interest according to professional and social expectations. The negative effects on quality of life and the large number of involved patients emphasize the need its investigation. MATERIAL/METHODS: The bedside measurement of simple and choice reaction times (sRT and cRT) has the objectivity of cortical evoked potential analysis without the need for EEG instrumentation and laboratory. This is a functional assessment similar to neuropsychological tests, but requires a significantly shorter time and is less demanding for the patient. RESULTS: Fifty patients who had undergone open heart surgery were investigated. Statistically significant positive correlation of sRT and cRT prolongation and perfusion time was found. At the same time there were no statistically significant changes in mean sRT and cRT values before (sRT: 208+/-54 s, cRT: 369+/-59 s) and after (sRT: 229+/-67 s, cRT: 392+/-105 s) the surgery, probably due to the inhomogeneous patient population. The weak correlation (coefficients: 0.1418-0.8484) for sRT and cRT changes as a function of perfusion time confirms the presence of other factors of postoperative brain damage. CONCLUSIONS: The investigated bedside test is clinically feasible, simple, and can be completed within 30 minutes. Further studies are encouraged to compare this method with other tests in a larger, stratified cardiac surgery population.

[Association between birth weight and childhood obesity in a Budapest metropolitan survey]. / A születési testtömeg és a gyermekkori elhízás kapcsolata egy fôvárosi felmérés alapján.

INTRODUCTION: According to epidemiological investigations, association between birth weight and overweight and obesity in childhood/adolescence is ambiguous. AIM: The purpose of the study was to investigate the association between birth weight and overweight and obesity in childhood and adolescence. METHODS: Birth and actual anthropometric data of school children and secondary school students from metropolitan schools were analyzed. Overweight/obesity were established by standardized (sex, age) body mass index, and obesity also by body fat percent. RESULTS: Data of 1,334, 7- to 19-year-old children and adolescents (725 boys and 609 girls) were evaluated. Prevalence of overweight/obesity was similar in the case of persons with low (19.36%) and normal birth weight (18.96%), while in the case of persons with high birth weight this rate was 25.98%. Based on body fat percent, the prevalence of obesity in the latter group was also higher than in groups with low and normal birth weight (18.11% vs. 12.89% and 12.66%). CONCLUSIONS: Among macrosomic babies the rate of overweight and obesity is higher than among normal or low-birth-weight babies, particularly in childhood.

Cellular Phone Irradiation of the Head Affects Heart Rate Variability Depending on Inspiration/Expiration Ratio.

BACKGROUND: Mobile phones may have harmful health effects and clinical examinations report ambiguous results of exposure concerning neurophysiological and cardiovascular actions. MATERIALS AND METHODS: This study investigated heart rate asymmetry (HRA) and heart rate variability (HRV) parameters with 1:2 and 1:1 metronome-paced inspiration/expiration ratios during short-term 1,800MHz GSM cellular phone exposure in 20 healthy volunteers. RESULTS: Significant HRA changes by Porta and Guzik indices were not found on exposure compared to sham exposure. Time-domain HRV parameters on exposure showed significant differences at 1:1 paced, but not at 1:2 paced breathing compared to sham exposure. A mild post-exposure effect was observed regarding root mean square of successive RR-differences. CONCLUSION: The findings reflect persisting acute effects of GSM handset emission on the autonomic nervous system. Exploring its influences on health status and survival needs further studies. Symmetrical breathing can be used as a sensitizing factor in other HRV/HRA analysis studies.

Monitoring urinary orosomucoid in patients undergoing cardiac surgery: A promising novel inflammatory marker.

BACKGROUND: Urinary biomarkers might provide non-invasive tool for monitoring of systemic processes. We aimed to investigate the time-course of urinary orosomucoid (u-ORM) excretion after cardiac surgery hypothesizing that u-ORM is an early and sensitive marker of systemic inflammatory activation. METHODS: During a 5-day follow-up study we monitored u-ORM levels in cardiovascular patients who underwent on-pump cardiac surgery (n=38). The patients baseline data were compared to healthy control individuals (n=40). u-ORM was measured by a newly developed automated turbidimetric assay and values were referred to urinary creatinine and expressed as u-ORM/u-CREAT (mg/mmol). RESULTS: The cardiovascular patients showed slightly increased baseline u-ORM excretion compared to healthy controls (0.29 vs 0.08mg/mmol, p<0.001). After cardiac surgery, a rapid 10-fold elevation in u-ORM/u-CREAT levels was found. The values remained high till the 3rd postoperative day, and they then decreased significantly (p<0.01) on the 5th day after surgery. u-ORM/u-CREAT mirrored well the perioperative tendency of hs-CRP levels, but it did not follow the non-decreasing kinetics of serum ORM concentrations during the follow-up. u-ORM/u-CREAT correlated significantly (p<0.001) with inflammatory parameters (hs-CRP, se-ORM, WBC). CONCLUSIONS: We described u-ORM as an early and sensitive marker of inflammatory activation. The rapid elevation of u-ORM/u-CREAT after surgery and its postoperative kinetics could reflect the magnitude of inflammatory response better than serum ORM and similar to hs-CRP. u-ORM measurements might provide a novel non-invasive tool for real-time monitoring of systemic inflammation, however further investigations are required to confirm it.

Monitoring of L-Arginine and Endogenous Dimethylarginines in Survivor Septic Patients - A Pilot Study.

BACKGROUND/AIM: Nitric oxide (NO) pathway plays a major role in the development and advancement of inflammation. We aimed to design a study and investigate its feasibility to show the changes of L-arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), which are important regulators of the NO pathway. PATIENTS AND METHODS: Concentrations of L-arginine, ADMA and SDMA were measured by liquid chromatography-tandem mass spectrometry. Seventeen septic survival patients were enrolled and blood samples were obtained on the first, third and fifth day after the diagnosis of sepsis. Sixteen non-septic matched controls were recruited. RESULTS: ADMA levels on admission correlated well with sequential organ failure assessment (SOFA) score. During the follow-up, L-arginine/ADMA ratio increased significantly from day 1 to day 3 (p=0.005), then decreased from day 3 to day 5 (p=0.023). CONCLUSION: This study design seems feasible to investigate changes of L-Arginine, ADMA and SDMA in sepsis survival patients.

Short-term response of metabolic hormones to coronary artery bypass surgery.

PURPOSE: To explore the response pattern of plasma adipokine and ghrelin levels to coronary artery bypass graft (CABG) surgery in patients with (on-pump) and without (off-pump) cardiopulmonary bypass (CPB). MATERIAL/METHODS: Sixteen consecutive patients (age: 62 ± 10 years, male: 10) with obstructive coronary artery disease (CAD) who underwent elective CABG surgery with CPB and intraoperative GIK infusion were selected for on-pump group and 19 CAD patients (age: 63 ± 10 years, male: 16) were included in the off-pump group. Blood samples were taken before, during and after surgery. Intraoperative samples were withdrawn simultaneously for peripheral vein and sinus coronarius (SC). Plasma adipokine concentrations were measured by ELISA, those of ghrelin by RIA kits. RESULTS: In response to surgical intervention there was an early, transient fall in plasma levels of adiponectin (p<0.0001) and resistin (p=0.002) followed by an increase to approach their initial values. Plasma ghrelin also increased (p=0.045), this increase, however, was confined to the period of GIK supported CPB. Plasma insulin (p=0.003) and resistin (p=0.009) was significantly higher in the peripheral vein than in SC. The perioperative hormone profile of patients without CPB (off-pump) proved to be comparable to that of on-pump patients in spite of the insulin administration and greater oxidative and inflammatory stress. CONCLUSIONS: Adipose tissue-derived factors appear to mediate the metabolic and vascular changes that occur in patients with CABG surgery. Epicardial adipose tissue is unlikely to have major contribution to the development of CAD as adipokines are not elevated in SC independent of the mode of intervention.

The assessment of neural injury following open heart surgery by physiological tremor analysis.

INTRODUCTION: The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor. MATERIAL AND METHODS: We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3(rd) to 5(th) post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test. RESULTS: We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p < 0.01). The magnitude of the shift was not significantly higher for females than for males (p < 0.157). We found no significant difference between the shift and the cross-clamp or perfusion time (p < 0.6450). CONCLUSIONS: The assessment of physiological tremor by means of our novel, feasible method may provide a deeper insight into the mechanism of central nervous system damage associated with open heart surgery.

Effects of coronary revascularization with or without cardiopulmonary bypass on plasma levels of asymmetric dimethylarginine.

OBJECTIVES: We measured and compared serum asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-arginine levels in patients undergoing coronary artery revascularization. METHODS: Two groups of patients with coronary artery disease were subjected to coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB; n = 20) or with off-pump CABG surgery (OPCABG; n = 21). Blood samples for measurements of ADMA, SDMA, and L-arginine were withdrawn and determined by liquid chromatography-tandem mass spectrometry from the coronary sinus (CS) and from the peripheral vein. RESULTS: On the basis of the intraoperative (CS) samples, ADMA levels rose in the CPB group (F = 0.416, P < 0.685 and F = 14.751, P < 0.001 for OPCABG and CPB groups, respectively). A similar significant increase of ADMA was observed in the peripheral blood (F = 30.738, P < 0.001) during CPB, whereas ADMA levels remained unchanged during OPCABG. The time course of L-arginine levels was significantly different in the blood samples from CS (F = 3.255, P<0.05), when compared with samples from the peripheral blood (F = 3.255, P < 0.05). The values of the L-arginine/ADMA ratio were significantly higher in the OPCABG group at baseline and on the first postoperative day compared with the results of the CPB group (178.29 ± 11.56 vs. 136.28 ± 13.72 and 129.43 ± 7.08 vs. 106.8 ± 6.9 for OPCABG and CPB groups, respectively). CONCLUSION: Plasma levels of ADMA, SDMA, L-arginine, and L-arginine/ADMA ratio are reliable and feasible markers of an early ischemia-reperfusion injury. During CPB operation, the plasma concentration of ADMA increased significantly and remained elevated until the first postoperative day due to extensive ischemia-reperfusion injury caused by CPB.

Invasive validation of a new oscillometric device (Arteriograph) for measuring augmentation index, central blood pressure and aortic pulse wave velocity.

BACKGROUND: The importance of measuring aortic pulse wave velocity (PWVao), aortic augmentation index (Aix) and central systolic blood pressure (SBPao) has been shown under different clinical conditions; however, information on these parameters is hard to obtain. The aim of this study was to evaluate the accuracy of a new, easily applicable oscillometric device (Arteriograph), determining these parameters simultaneously, against invasive measurements. METHODS: Aortic Aix, SBPao and PWVao were measured invasively during cardiac catheterization in 16, 55 and 22 cases, respectively, and compared with the values measured by the Arteriograph. RESULTS: We found strong correlation between the invasively measured aortic Aix and the oscillometrically measured brachial Aix on either beat-to-beat or mean value per patient basis (r = 0.9, P < 0.001; r = 0.94, P < 0.001), which allowed the noninvasive calculation of the aortic Aix without using generalized transfer function. Similarly strong correlation (r = 0.95, P < 0.001) was found between the invasively measured and the noninvasively calculated central SBPao; furthermore, the BHS assessment of the paired differences fulfilled the 'B' grading. The PWVao values measured invasively and by Arteriograph were 9.41 ± 1.8 m/s and 9.46 ± 1.8 m/s, respectively (mean ± SD); furthermore, the Pearson's correlation was 0.91 (P < 0.001). The limits of agreement were 11.4% for aortic Aix and 1.59 m/s for PWVao. CONCLUSION: Aix, SBPao and PWVao, measured oscillometrically, showed strong correlation with the invasively obtained values. The observed limits of agreement are encouragingly low for accepting the method for clinical use. Our results suggest that the PWVao values, measured by Arteriograph, are close to the true aortic PWV, determined invasively.

Effects of stent implementation on plasma levels of asymmetric dimethylarginine in patients with or without ST-segment elevation acute myocardial infarction.

The study was designed to compare the response pattern of plasma l-arginine and methylarginines to stent placement in patients with or without ST segment elevation myocardial infarction (STEMI). Two groups of patients with obstructive coronary artery disease (OCAD) undergoing percutaneous coronary intervention (PCI) with stenting were enrolled in the study. Group I consisted of 16 patients with STEMI, whereas group II included 24 patients without STEMI (controls). Before PCI and at <1 h, 5 and 30 days after reperfusion, blood samples were taken for measurement of l-arginine and methylarginines. L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethylarginine (MMA) and l-ornithine plasma levels were measured by LC-MS-MS. Arginine methylation index (Arg-MI) was calculated according to the formula, Arg-MI = (ADMA+SDMA)/MMA. In patients without STEMI, stenting induced a prompt and sustained depression of ADMA (p<0.000), and l-ornithine (p<0.000) with simultaneous increase of l-arginine (p<0.001), l-arginine/ADMA ratio (p<0.000) and an inconsistent change in MMA. Arg-MI remained at the baseline value. By contrast, STEMI patients responded to stent placement with a variable increase in l-arginine (p<0.01), ADMA (p<0.069), SDMA, MMA (p<0.01) and l-ornithine (p<0.000), whereas there was an early fall of Arg-MI after stenting, followed by a steady increase approaching the initial values. The differences in the time-course for ADMA (p<0.000), MMA (p<0.007), Arg-MI (p<0.01) and l-ornithine (p<0.003) proved to be significant between the STEMI and control group. It can be concluded therefore, that stent placement improves endothelial dysfunction in patients with OCAD when it is not complicated by STEMI.