Attila Cziraki

Reference values of aortic pulse wave velocity in a large healthy population aged between 3 and 18 years.

Objective: The measurement of aortic pulse wave velocity (PWVao) is an accepted marker in stratifying individual cardiovascular risk in adults. There is an increasing volume of evidence concerning impaired vascular function in different diseases in paediatric populations, but, unfortunately, only a few studies are available on the measurement of normal PWVao values in children. The aim of our study was to determine the reference values of PWVao in a large healthy population using a newly developed technique. Methods: Three thousand, three hundred and seventy-four healthy individuals (1802 boys) aged 3–18 years were examined by an invasively validated, occlusive, oscillometric device. Results: The mean PWVao values increased from 5.5 ± 0.3 to 6.5 ± 0.3 m/s (P < 0.05) in boys and from 5.6 ± 0.3 to 6.4 ± 0.3 m/s (P < 0.05) in girls. The increase, however, was not constant, and the values exhibited a flat period between the ages of 3 and 8 years in both sexes. The first pronounced increase occurred at the age of 12.1 years in boys and 10.4 years in girls. Moreover, between the ages of 3 and 8 years, the brachial SBP and mean blood pressures increased continuously and gradually, whereas the PWVao remained unchanged. By contrast, beyond the age of 9 years, blood pressure and aortic stiffness trends basically moved together. Conclusion: Our study provides the largest database to date concerning arterial stiffness in healthy children and adolescents between the ages of 3 and 18 years, and the technology adopted proved easy to use in large paediatric populations, even at a very young age.

cGMP Accumulation and Gene Expression of Soluble Guanylate Cyclase in Human Vascular Tissue

Gene expression of soluble guanylate cyclase (sGC) and cGMP accumulation in response to sodium nitroprusside (SNP) were studied in cultured human vascular cells and freshly harvested vascular tissue. As revealed by reverse transcriptase‐polymerase chain reaction, cultured smooth muscle and endothelial cells, as well as freshly isolated human vascular tissue, express mRNA for the α3 and β3 subunits but not for the α2 or β2 sGC. In cultured human cells, expression of the α3 and β3 subunits is evident even in the absence of increased cGMP accumulation in response to SNP. cGMP accumulation in cultured human cells from different vascular beds typically increased two‐ to fivefold (maximum of 11.4‐fold) over baseline following stimulation with 100 μM SNP. Bovine, murine, canine, and avian vascular smooth muscle cells accumulated similar or lower amounts of cGMP than human cells, whereas porcine, rat, and rabbit smooth muscle cells accumulated greater amounts of cGMP. In freshly harvested human vessels, cGMP accumulation in response to SNP was found to increase fifteenfold over baseline. In contrast to the SNP‐induced cGMP accumulation, cGMP levels in response to the particulate guanylate cyclase activator atriopeptin II were equal or greater in cultured human cells than in fresh human vascular tissue. We conclude that human vascular cells (fresh and cultured) express the mRNA for both a large (α3) and a small (β3) sGC subunit and that fresh human cells are more sensitive to SNP stimulation.

Quantification of pulmonary capillary endothelium-bound angiotensin converting enzyme inhibition in man

Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme expressed abundantly on the pulmonary capillary endothelium and recognized as the site for the conversion of circulating angiotensin I to II. In the present study, we have applied recently developed methodologies for assaying pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product (3H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage, at baseline (T(0)) and at 15 min (T(15)) and 2 h (T(120)) after intravenous administration of 1.5 g/kg enalaprilat in 12 normotensive subjects. This treatment had no significant effect on mean arterial pressure (91+/- 6 vs. 84 +/- 7 vs. 88 +/- 6 mm Hg for T(0), T(15) and T(120), respectively), but significantly decreased serum and PCEB ACE activities. When normalized to predrug (T(0)) activity levels, enalaprilat inhibited PCEB and serum ACE activities at T(15) 74 +/- 6% and 68 +/- 6%, respectively. However, 2 h after enalaprilat (T(120)), PCEB ACE inhibition was maintained at 66 +/- 7%, whereas serum ACE inhibition was reduced to 46 +/- 8% (P<.01 from PCEB ACE), suggesting a preferential PCEB ACE inhibitory effect of enalaprilat.

Inhibition of pulmonary endothelial angiotensin converting enzyme activity by trandolaprilat in vivo

The purpose of the present study was to contrast a commonly used ACE inhibitor (enalaprilat) with a novel ACE inhibitor (trandolaprilat) in their ability to inhibit 1) pulmonary capillary endothelial‐bound ACE activity in vivo, 2) arterial pressure responses to i.v. angiotensin I and bradykinin, and 3) selected tissue ACE activity ex vivo, in rabbits. Pulmonary capillary endothelium‐bound ACE activity in vivo was estimated via the single pass transpulmonary hydrolysis of the substrate 3H‐Benzoyl‐Phenylalanyl‐Alanyl‐Proline (BPAP). Doses of acutely administered trandolaprilat (8 μg/kg) or enalaprilat (10 μg/kg) were equieffective in reducing the pressor response to angiotensin I. At these doses, trandolaprilat produced a greater inhibition of pulmonary capillary endothelial‐bound ACE activity (66.5 ± 4.7% reduction of baseline BPAP metabolism vs. 52.7 ± 4.2% by enalaprilat, P < 0.05). Chronically administered trandolaprilat (8 μkg/day for 8 days) was more effective than enalaprilat (either 8 μg/kg/day or 10 μg/kg/day for 8 days) in reducing the angiotensin‐1 induced increase in mean arterial pressure (increases of 9.7 ± 1.4 mmHg vs. 20.3 ± 2.3 mmHg and 19.1 ± 5.7 mmHg respectively; P < 0.01), as well as in reducing BPAP metabolism. In agreement with in vivo data, trandolaprilat was 5.5‐, 3.6‐, and 2.5‐times more effective than enalaprilat in reducing ACE activities in the aorta, left ventricle, and lung, respectively. We conclude that trandolaprilat is a more potent, longer acting, and more tissue‐selective ACE inhibitor than enalaprilat, and that the method outlined here can be used to aid in the development of tissue‐specific ACE inhibitors. Drug Dev. Res. 41:22–30, 1997.

Unaltered pulmonary capillary surface area in the presence of changing arterial resistance

We hypothesized that capillary recruitment may not be solely dependent on extracapillary factors. To test this hypothesis, rabbits were anesthetized and placed on total cardiac bypass at a constant, physiological pulmonary blood flow. Vascular occlusion techniques were combined with measurement of the transpulmonary metabolism of an angiotensin-converting enzyme substrate, allowing the concomitant assessment of changes in segmental resistances and dynamically perfused capillary surface area. Intra-arterial serotonin infusion increased upstream pulmonary vascular resistances without affecting dynamically perfused capillary surface area. Intra-arterial isoproterenol infusion diminished serotonin-induced increased upstream resistances, also without affecting capillary surface area. These findings support the hypothesis that pulmonary capillary recruitment may not be solely dependent on extracapillary factors.We hypothesized that capillary recruitment may not be solely dependent on extracapillary factors. To test this hypothesis, rabbits were anesthetized and placed on total cardiac bypass at a constant, physiological pulmonary blood flow. Vascular occlusion techniques were combined with measurement of the transpulmonary metabolism of an angiotensin-converting enzyme substrate, allowing the concomitant assessment of changes in segmental resistances and dynamically perfused capillary surface area. Intra-arterial serotonin infusion increased upstream pulmonary vascular resistances without affecting dynamically perfused capillary surface area. Intra-arterial isoproterenol infusion diminished serotonin-induced increased upstream resistances, also without affecting capillary surface area. These findings support the hypothesis that pulmonary capillary recruitment may not be solely dependent on extracapillary factors.

Early Detection of Lung Endothelial Dysfunction in Man

Pulmonary vascular endothelial cells express a variety of transporter and enzyme proteins which are known or suspected modulators of cardiovascular homeostasis and are susceptible to injury (Ryan, U.S., 1987). Over the past decade, studies by us and other investigators have accumulated considerable experimental evidence suggesting that the activity of pulmonary capillary endothelium-bound angiotensin converting enzyme (ACE), a prominent endothelial ectoenzyme which is uniformly distributed throughout the vasculature, can be assayed repeatedly, accurately and reproducibly, in vivo (Ryan, J. W., 1977, 1991; Catravas et alt 1981, 1983). Reduced endothelium-bound ACE activity is the earliest yet known manifestation of impeding lung injury in various animal models of lung damage, in vivo (e.g., hyperoxia, irradiation, bleomycin, activated neutrophil, etc.) (Bakhle, 1979; Catravas et al, 1984, 1989; Gillisetal, 1986; McCormick etal, 1987; Tovvonen etal, 1981). Based on these findings, we have hypothesized that monitoring of changes in pulmonary capillary endothelium-bound ACE activity may be used as a diagnostic test to aid in the early detection of lung injury in man.

Transcutaneous Carbon Dioxide Treatment Is Capable of Reducing Peripheral Vascular Resistance in Hypertensive Patients

Aim: We aimed to investigate the effects of a single carbon dioxide (CO2) treatment on arterial stiffness by monitoring the changes of aortic pulse-wave velocity (PWV) and aortic augmentation index (AIXao), which are indicators of arterial stiffness. Patients and Methods: PWV and AIXao were measured by an invasively validated oscillometric device. The measurements of stiffness parameters were performed before the CO2 treatment, and at 1, 4 and 8 h after the first treatment. Results: Thirty-one patients were included. No significant changes were found in PWV. AIXao decreased significantly 1 h and 4 h after CO2 treatment compared to baseline values (p=0.034 and p<0.001). AIXao increased 8 h after the CO2 treatment, but remained significantly lower than baseline AIXao values (p=0.016). Conclusion: CO2 treatment is capable of reducing peripheral vascular resistance. We hypothesize that CO2 is not only a temporal vasodilator but is also capable of activating vasodilation pathways.

Prevalence of Overweight and Obesity in Hungarian Children and Adolescents

Background/Aims: The prevalence of overweight and obesity in children and adolescents is increasing worldwide, and this condition is a risk factor for cardiovascular mortality. The aim of this study was to assess the prevalence of overweight and obesity among the 3–18-year-old population in Szolnok City and the surrounding areas. Methods: Anthropometric data from healthy, white individuals recruited from nursery, elementary, and secondary schools were used to assess the prevalence of obesity and overweight in Szolnok City and the surrounding area, Jász-Nagykun-Szolnok county, Hungary. Healthy subjects numbering 6,824 (54% boys) were included; overweight and obesity were defined according to the relevant guidelines. Results: Overweight individuals constituted 13.4% of the population and 6.6% were obese. The total prevalence was higher in boys (21.6%) than in girls (18.1%). The peak of the prevalence was observed at age 10 in both sexes (boys 33%, girls 27%) followed by a gradual decrease, which was more significant in the case of girls. Conclusions: On the basis of the recent Hungarian data, we have not detected any changes in overweight and obesity in the age group 3–9 years and we have found a significant decrease in the age group 7–14 years. Prevention of overweight and obesity in early childhood is essential.

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.

Preoperative Care, Anesthesia and Early Postoperative Care of Vascular Patients

The changes in the operation technic in the last twenty years may reduce morbidity and mortality of traditionally high – risk vascular surgical procedures. (White CJ&Gray WA, 2007) The indrease of median age, the number of elderly patients will also elevate the number of vascular procedures. Careful preoperative evaluation of patients undergoing vascular surgical intervention holds great significance since this group of patients has almost the highest percentage of accompanying diseases with poor outcome. It is wellknown that vascular disease – irrespectively of its manifestation – is a generalized disorder, the majority of patients with vascular disease smoke and have chronic pulmonary disease, also suffers from diabetes and hypertension. Hypertension and diabetes are often associated with coronary artery disease which determines the short and long-term survival of vascular procedures. Coronary artery disease is one of the most frequent cause of the perioperative mortality and morbidity (1-5%). Goldman et al.( drew the attention to the frequency of cardiac complication of vascular operations as far back as 1977 and aimed to establish a multi-factorial score index. Based on detailed surveys which covered a large patient population the perioperative incidence of myocardial infarction among patient undergoing vascular surgical procedures is 2, 1 – 8, 0 %, whilst the mortality is 0, 6 – 5, 4 %. These examinations did not consider the type of operations – open or endovascular. Beside Goldman’s classic risk index numerous task forces have established their own score system for the assessment of perioperative cardiac risk. All of these highlight the significance of the fact that after being aware of the clinical risk, consultation and mutual decision making of cardiologists, anesthetists and vascular surgeons in evaluation the long-term efficiency and risk ratio is essential. The most important weak point of all score system is the utilization of data derived from patients underwent elective operations. Kertai et al. developed a simplified risk index, which is suitable for the assessment of perioperative mortality of either acute or elective patients undergoing vascular surgical operations. The American College of Cardiologist and the American Heart Association has developed a guideline (2007) for the assessment of Cardiovascular risk among patients with different diseases who are undergoing non-cardiac surgery. This guideline includes the risk assessment for the patient undergoing vascular surgery. Three categories of cardiac risk have been classified in the guideline, high, intermediate and low. High cardiac risk involves the history of acute