Simultaneous biventricular pressure-volume analysis in rats.

The pressure-volume (PV) analysis is used for an accurate assessment of load-independent cardiac function and is important for the study of cardiovascular diseases and various therapeutic modalities. PV analysis is often performed on one of the ventricles, or on both ventricles but sequentially. Since both ventricles interact with each other and their functions are mutually interdependent, especially in various disease conditions such as pulmonary hypertension or heart failure, it is important to quantify the function of both ventricles at the same time. Therefore, our aim was to describe a standardized protocol for simultaneous right (RV) and left (LV) ventricle of PV analysis, including an especially controllable preload reduction manoeuver. Our second aim was to test whether simultaneous catheterization of both LV and RV is necessary for the determination of biventricular PV relationship compared to sequential measurement of both ventricles separately. In this article, we showed the feasibility and the value of simultaneous biventricular PV analysis in the measurement of contractility parameters (end-systolic pressure-volume relationship (ESPVR), ventricular pressure over time (dP/dt)max, divided by end-diastolic volume (dP/dt max-EDV)) with a comparison to the sequential measurement of the RV and LV ventricles separately. We described in detail the protocol for simultaneous biventricular PV analysis in rats using a pair of conductance-micromanometer catheters with a preload-reducing manoeuver using balloon catheter inflation in the inferior vena cava. We also described technical tips and show examples of PV loop data obtained in normotensive and hypertensive rats, with and without heart failure due to volume overload. This protocol could be useful for scientists studying hemodynamics and cardiac contractility in various models of cardiovascular diseases with a focus on biventricular differences and ventricular interdependence.

Intraventricular placement of a spring expander does not attenuate cardiac atrophy of the healthy heart induced by unloading via heterotopic heart transplantation.

An important complication of the prolonged left ventricle assist device support in patients with heart failure is unloading-induced cardiac atrophy which proved resistant to various treatments. Heterotopic heart transplantation (HTx) is the usual experimental model to study this process. We showed previously that implantation of the newly designed intraventricular spring expander can attenuate the atrophy when examined after HTx in the failing heart (derived from animals with established heart failure). The present study aimed to examine if enhanced isovolumic loading achieved by implantation of the expander would attenuate cardiac post-HTx atrophy also in the healthy heart. Cardiac atrophy was assessed as the ratio of the transplanted-to-native heart weight (HW) and its degree was determined on days 7, 14, 21 and 28 after HTx. The transplantation resulted in 32±3, 46±2, 48±3 and 46±3 % HW loss when measured at the four time points; implantation of the expander had no significant effect on these decreases. We conclude that enhanced isovolumic loading achieved by intraventricular implantation of the expander does not attenuate the development of cardiac atrophy after HTx in the healthy heart. This indicates that such an approach does not represent a useful therapeutic measure to attenuate the development of unloading-induced cardiac atrophy.

Detection and quantitation of iron in ferritin, transferrin and labile iron pool (LIP) in cardiomyocytes using 55Fe and storage phosphorimaging.

Dysregulated iron metabolism has a detrimental effect on cardiac function. The importance of iron homeostasis in cardiac health and disease warrants detailed studies of cardiomyocyte iron uptake, utilization and recycling at the molecular level. In this study, we have performed metabolic labeling of primary cultures of neonatal rat cardiomyocytes with radioactive iron coupled with separation of labeled iron-containing molecules by native electrophoresis followed by detection and quantification of incorporated radioiron by storage phosphorimaging. For the radiolabeling we used a safe and convenient beta emitter 55Fe which enabled sensitive and simultaneous detection and quantitation of iron in cardiomyocyte ferritin, transferrin and the labile iron pool (LIP). The LIP is believed to represent potentially dangerous redox-active iron bound to uncharacterized molecules. Using size-exclusion chromatography spin micro columns, we demonstrate that iron in the LIP is bound to high molecular weight molecule(s) (≥5000 Da) in the neonatal cardiomyocytes.

Effect of angiotensin-converting enzyme blockade, alone or combined with blockade of soluble epoxide hydrolase, on the course of congestive heart failure and occurrence of renal dysfunction in Ren-2 transgenic hypertensive rats with aorto-caval fistula.

We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR. The treatment regimens were started one week after ACF creation and the follow-up period was 50 weeks. RAS was blocked using angiotensin-converting enzyme inhibitor (ACEi, trandolapril, 6 mg/l) and sEH with an sEH inhibitor (sEHi, c-AUCB, 3 mg/l). Renal hemodynamics and excretory function were determined two weeks post-ACF, just before the onset of decompensated phase of CHF. 29 weeks post-ACF no untreated animal survived. ACEi treatment greatly improved the survival rate, to 84 % at the end of study. Surprisingly, combined treatment with ACEi and sEHi worsened the rate (53 %). Untreated ACF TGR exhibited marked impairment of renal function and the treatment with ACEi alone or combined with sEH inhibition did not prevent it. In conclusion, addition of sEHi to ACEi treatment does not provide better protection against CHF progression and does not increase the survival rate in ACF TGR: indeed, the rate decreases significantly. Thus, combined treatment with sEHi and ACEi is not a promising approach to further attenuate renal dysfunction and retard progression of CHF.

Effects of increased myocardial tissue concentration of myristic, palmitic and palmitoleic acids on the course of cardiac atrophy of the failing heart unloaded by heterotopic transplantation.

The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HT(x)) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HT(x) was determined on days 7, 14, 21 and 28 after HT(x) in recipients of either healthy or failing hearts. HT(x) of healthy hearts resulted in 23+/-3, 46+/-3, 48+/-4 and 46+/-4 % HW loss at the four time-points. HT(x) of the failing heart resulted in even greater HW losses, of 46+/-4, 58+/-3, 66+/-2 and 68+/-4 %, respectively (P<0.05). Activation of "fetal gene cardiac program" (e.g. beta myosin heavy chain gene expression) and "genes reflecting cardiac remodeling" (e.g. atrial natriuretic peptide gene expression) after HT(x) was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HT(x) failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy.

Inhibition of soluble epoxide hydrolase does not improve the course of congestive heart failure and the development of renal dysfunction in rats with volume overload induced by aorto-caval fistula.

The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/l in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue.

L-arginine in combination with sildenafil potentiates the attenuation of hypoxic pulmonary hypertension in rats.

Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels correlates with concentration of L-arginine as well as activity of phosphodiesterase-5 enzyme (PDE-5). We tested a hypothesis whether a combination of L-arginine and PDE-5 inhibitor sildenafil has an additive effect in reduction of the hypoxic pulmonary hypertension (HPH) in rats. Animals were exposed to chronic normobaric hypoxia for 3 weeks. In the AH group, rats were administered L-arginine during chronic hypoxic exposure. In the SH group, rats were administered sildenafil during chronic hypoxic exposure. In the SAH group, rats were treated by the combination of L-arginine as well as sildenafil during exposure to chronic hypoxia. Mean PAP, structural remodeling of peripheral pulmonary arterioles (%DL) and RV/LV+S ratio was significantly decreased in the SAH group compared to hypoxic controls even decreased compared to the AH and the SH groups in first two measured parameters. Plasmatic concentration of cGMP and NOx were significantly lower in the SAH group compared to hypoxic controls. We demonstrate that NO synthase substrate L-arginine and phosphodiesterase-5 inhibitor sildenafil administered in combination are more potent in attenuation of the HPH compared to a treatment by substances given alone.

Associations between cardiac fibrosis and permanent atrial fibrillation in advanced heart failure.

Atrial fibrosis is considered as the basis in the development of long-standing atrial fibrillation (AF). However, in advanced heart failure (HF), the independent role of fibrosis for AF development is less clear since HF itself leads to atrial scarring. Our study aimed to differentiate patients with AF from patients without AF in a population consisting of patients with advanced HF. Myocardial samples from the right atrial and the left ventricular wall were obtained during heart transplantation from the explanted hearts of 21 male patients with advanced HF. Long-standing AF was present in 10 of them and the remaining 11 patients served as sinus rhythm controls. Echocardiographic and hemodynamic measurements were recorded prior to heart transplantation. Collagen volume fraction (CVF), transforming growth factor-beta (TGF-beta), and connective tissue growth factor (CTGF) expression in myocardial specimens were assessed histologically and immunohistochemically. The groups were well matched according to age (51.9+/-8.8 vs. 51.3+/-9.3 y) and co-morbidities. The AF group had higher blood pressure in the right atrium (13.6+/-7.7 vs. 6.0+/-5.0 mmHg; p=0.02), larger left atrium diameter (56.1+/-7.7 vs. 50+/-5.1 mm; p=0.043), higher left atrium wall stress (18.1+/-2.1 vs. 16.1+/-1.7 kdynes/m(2); p=0.04), and longer duration of HF (5.0+/-2.9 vs. 2.0+/-1.6 y, p=0.008). There were no significant differences in CVF (p=0.12), in CTGF (p=0.60), and in TGF-beta expression (p=0.66) in the atrial myocardium between the two study groups. In conclusions, in advanced HF, atrial fibrosis expressed by CVF is invariably present regardless of occurrence of AF. In addition to atrial wall fibrosis, increased wall stress might contribute to AF development in long-standing AF.

Is severe pulmonary hypertension a contraindication for orthotopic heart transplantation? Not any more.

Pulmonary hypertension (PH) unresponsive to pharmacological intervention is considered a contraindication for orthotopic heart transplantation (OHTX) due to risk of postoperative right-heart failure. In this prospective study, we describe our experience with a treatment strategy of improving severe PH in heart transplant candidates by means of ventricular assist device (VAD) implantation and subsequent OHTX. In 11 heart transplantation candidates with severe PH unresponsive to pharmacological intervention we implanted VAD with the aim of achieving PH to values acceptable for OHTX. In all patients we observed significant drop in pulmonary pressures, PVR and TPG (p < 0.001 for all) 3 months after VAD implantation to values sufficient to allow OHTX. Seven patients underwent transplantation (mean duration of support 216 days) while none of patients suffered right-side heart failure in postoperative period. Two patients died after transplantation and five patients are living in very good condition with a mean duration of 286 days after OHTX. In our opinion, severe PH is not a contraindication for orthotopic heart transplantation any more.

Sildenafil is more selective pulmonary vasodilator than prostaglandin E1 in patients with pulmonary hypertension due to heart failure.

In some patients, heart failure (HF) is associated with increased pulmonary vascular resistance (PVR). The magnitude and the reversibility of PVR elevation affect the HF management. Sildenafil has been recently recognized as potent PVR-lowering drug in HF. The aim of the study was to compare hemodynamic effects and pulmonary selectivity of sildenafil to prostaglandin E(1) (PGE(1)). Right-heart catheterization was performed in 13 euvolemic advanced HF patients with elevated PVR (6.3+/-2 Wood's units). Hemodynamic parameters were measured at the baseline, during i.v. infusion of PGE1 (alprostadil 200 ng · kg(-1) · min(-1)) and after 40 mg oral dose of sildenafil. Both drugs similarly reduced systemic vascular resistance (SVR), but sildenafil had higher effect on PVR (-28 % vs. -49 %, p = 0.05) and transpulmonary pressure gradient than PGE(1). The PVR/SVR ratio--an index of pulmonary selectivity, did not change after PGE(1) (p = 0.7) but it decreased by -32 % (p = 0.004) after sildenafil. Both drugs similarly reduced pulmonary artery mean and wedge pressures and increased cardiac index (+27 % and +28 %). Sildenafil led more often to transplant-acceptable PVR while causing smaller drop of mean systemic pressure than PGE(1). In conclusion, vasodilatatory effects of sildenafil in patients with heart failure are more pronounced in pulmonary than in systemic circulation.

New insights into mechanisms of atrial fibrillation.

Although atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, precise mechanisms that lead to the onset and persistence of AF have not completely been elucidated. Over the last decade, outstanding progress has been made in understanding the complex pathophysiology of AF. The key role of ectopic foci in pulmonary veins as a trigger of AF has been recognized. Furthermore, structural remodeling was identified as the main mechanism for AF persistence, confirming predominant role of atrial fibrosis. Systemic inflammatory state, oxidative stress injury, autonomic balance and neurohormonal activation were discerned as important modifiers that affect AF susceptibility. This new understanding of AF pathophysiology has led to the emergence of novel therapies. Ablative interventions, renin-angiotensin system blockade, modulation of oxidative stress and targeting tissue fibrosis represent new approaches in tackling AF. This review aims to provide a brief summary of novel insights into AF mechanisms and consequent therapeutic strategies.

Hyperlipidemia is associated with altered levels of insulin-like growth factor-I.

Previous studies revealed altered levels of the circulating insulin-like growth factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3 alterations in subjects with moderate/severe hyperlipidemia but without any clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed in 56 patients with mixed hyperlipidemia (MHL; cholesterol >6.0 mmol/l, triglycerides >2.0 mmol/l), in 33 patients with isolated hypercholesterolemia (IHC; cholesterol >6.0 mmol/l, triglycerides <2.0 mmol/l), and in 29 healthy controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from controls by lower total IGF-I (164+/-60 vs. 209+/-73 ng/ml, p=0.01) and IGF-I /IGFBP-3 ratio (0.14+/-0.05 vs. 0.17+/-0.04, p=0.04). Compared to controls, MHL subjects had lower total IGF-I (153+/-54 ng/ml, p=0.0002) and IGFBP-3 (2.8+/-0.6 mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25+/-0.06, p<0.0001). Differences remained significant after the adjustment for clinical and biochemical covariates, except for triglycerides. Patients with both IHC and MHL have lower total IGF-I compared to controls. The mechanism is presumably different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP-3 ratio as a surrogate of free IGF-I.

Second derivative of the finger arterial pressure waveform: an insight into dynamics of the peripheral arterial pressure pulse.

The study investigated second derivative of the finger arterial pressure waveform (SDFAP) in 120 healthy middle-aged subjects and in 24 subjects with essential hypertension. SDFAP consists of 5 sequential waves 'a'-'e'. Their normalized magnitudes (B/A, C/A, D/A, and E/A) were calculated. In multivariate regression analysis, B/A and C/A correlated only with age. D/A independently correlated with age, heart period, mean blood pressure (MBP), body height, and gender. E/A independently correlated with age and MBP. D/A and E/A were higher (0.42+/-0.16 vs. 0.33+/-0.14, p = 0.05 and 0.63+/-0.15 vs. 0.45+/-0.14, p < 0.001), while B/A and C/A were lower (1.04+/-0.16 vs. 1.20+/-0.17, p = 0.002 and 0.09+/-0.15 vs. 0.26+/-0.20, p = 0.001) in hypertensives compared to sex- and age-matched controls. After the adjustment for MBP, heart period, and body mass index (ANCOVA), independent discriminative power was preserved only for indices B/A and C/A (p = 0.001 and 0.021, respectively). Therefore, B/A and C/A provide additional information about simple clinical characteristics and might reflect the structural alteration of the arterial wall in hypertensive subjects.

[Heart rate turbulence--a new ECG predictor for risk of sudden death]. / Turbulence srdecní frekvence--nový EKG prediktor rizika náhlé smrti.

Heart Rate Turbulence (HRT) is a newly described physiological chronotropic response of sinus rhythm following a single ventricular premature beat (VPB) consisting of early acceleration and later deceleration of heart rate. Using two large independent cohorts of postinfarction patients, the absence of HRT was retrospectively validated to be a potent multivariate risk predictor, stronger than a number of currently available risk stratifiers. Although exact pathophysiological mechanism of HRT remains speculative, it is now believed that HRT arises from the haemodynamic changes and baroreceptor reflexes that occur following a VPB. Therefore, HRT descriptors (Turbulence Onset and Turbulence Slope) may serve as very reasonable, Holter--based surrogates of baroreflex sensitivity available in clinical practice. The aim of this review is to summarise the current knowledge on pathophysiological mechanisms of HRT and to discuss practical problem of its detection.

Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT).

OBJECTIVE: It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia. Studies assessing the effects of fibrates on endothelium have been neglected. Therefore, we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia. METHODS: 29 otherwise healthy males (aged 47.4+/-7.8 years) with combined hyperlipidaemia (total cholesterol 7.55+/-1.20 mmol/l, triglycerides 5.41+/-4.54 mmol/l) were included into the randomised, single-blind, cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily--each of the drugs for a period of 10 weeks. Analysed biochemical parameters were as follows: serum total-, LDL- and HDL-cholesterol, apolipoproteins A-I and B, triglycerides, fibrinogen, uric acid, C-reactive protein (CRP), insulin, and homocysteine. Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery. Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow (PBF) representing the level of reactive hyperaemia and traditional flow-mediated dilatation (FMD). RESULTS: We observed a small improvement in FMD after both fenofibrate and atorvastatin (from 2.26% to 2.98% and 2.87%, respectively; NS). PBF increased from 448 ml/min to 536 ml/min after fenofibrate (P=0.04) and to 570 ml/min after atorvastatin (P=0.03). The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly (P-values of 0.82 and 0.47 for FMD and PBF, respectively). Significant correlations (P<0.01) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP (r=-0.60) and between both FMD and PBF, and insulinaemia (r=-0.48 and -0.56, respectively) only during treatment with fenofibrate. CONCLUSIONS: Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference. The PBF was superior to FMD for the detection of this improvement. The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy. The improvement of vascular reactivity during treatment with fenofibrate (opposed to atorvastatin) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance. The PBF was more reproducible than FMD because of considerably lower intra-subject variability.

Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy.

BACKGROUND: Homocysteine is associated with an increased risk of atherosclerosis. The administration of fibrates has been reported to significantly increase plasma homocysteine levels, a potentially adverse effect of fibrates. We investigated the hypothesis that concomitant treatment with fenofibrate and folic acid leads to a smaller increase in plasma total homocysteine levels than treatment with fenofibrate alone. METHODS: A randomized, open-label study compared the effect of micronized fenofibrate (200 mg daily) alone versus fenofibrate plus folic acid (10 mg every other day) on plasma homocysteine levels. Twenty-two patients with mixed hyperlipidemia participated. The 9-wk treatment period was preceded by a 4-wk wash-out period without hypolipidemic drugs. RESULTS: In patients treated with fenofibrate only, plasma homocysteine levels increased by 6.85 +/- 5.23 micromol/L (from 12.27 +/- 3.15 to 19.13 +/- 7.20 micromol/L); in patients treated with fenofibrate and folic acid, plasma homocysteine levels increased by 2.01 +/- 2.88 micromol/L (from 10.14 +/- 2.32 to 12.15 +/- 3.08 micromol/L). The difference in the homocysteine increase between the two groups was statistically significant at P = 0.014. CONCLUSIONS: Folic acid supplementation in patients treated with fenofibrate significantly reduced the increase in plasma homocysteine levels. More studies are needed to clarify whether amelioration of this side effect increases the clinical benefit of fibrates.

The changes of IGF binding proteins after rhGH administration to patients totally dependent on parenteral nutrition.

The objective was to study the effect of recombinant human growth hormone (rhGH) administration to patients with chronic malnutrition maintained on total parenteral nutrition (TPN) on the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) during a double-blind trial. After 1 week of TPN the patients were randomized into group I (placebo) or group II (rhGH). Samples were collected on the first day (start of the TPN) to measure basal values, the seventh day to study the effect of TPN and the 10th, 14th and 21st days to evaluate the rhGH effect. Basal laboratory evaluation, nutritional status and glucose tolerance were assessed using standard laboratory techniques. Radioimmunoassays were used to analyse IGF-I, free IGF-I (fIGF-I) and IGFBP1-3. Electrophoresis with Western ligand blotting and Western immunoblotting was applied to find the pattern of IGFBPs. TPN had no effect on the circulating IGF-I concentration and the pattern of IGFBPs present in the studied groups of patients. The rhGH administration led to significant increases of IGF-I, total IGFBP-3, glycosylated IGFBP-3 (39, 42 kDa) and the 29 kDa fragment of IGFBP-3 and the decrease of IGFBP-2 during the trial (P<0.05). The mean levels of IGFBP-1, fIGF-I and the parameters of nutritional status in group II during the trial were not significantly influenced by rhGH. However, it has been found that IGFBP-1 and fIGF-I levels were correlated with the levels of the weekly nitrogen balance of each patient in group II at the end of the trial. In spite of the significant changes of IGF-I, IGFBP-2, total IGFBP-3 and IGFBP-3 (29 kDa proteolytic fragment) after rhGH administration to patients with malnutrition, maintained on parenteral nutrition, the increase of nitrogen balance was seen only in patients who decreased their IGFBP-1 and increased bioavailable IGF-I as reflected by measurement of fIGF-I. The levels of IGFBP-1 may provide a useful marker of IGF-I bioavailability in monitoring the efficiency of the rhGH therapy in malnourished patients.

Cross-spectral analysis of heart rate and blood pressure modulations.

The cross-spectral analysis of heart rate (HR) and blood pressure (BP) variabilities provides "amplitude" and "phase" related measures. Compared to the amplitude measure, that is the baroreflex gain, the phase related measure characterizing the time lag between HR and BP oscillations has been studied to a much lesser extent. A population of 103 patients (73 men, 30 women, aged 53 +/- 12, range 20-82 years) referred for the management of coronary artery disease and/or hypertension were studied. In each subject, electrocardiogram and BP recordings were obtained in the supine and sitting positions of 5 minutes of rest (spontaneous respiration), 3 minutes of controlled respiration at 0.1 Hz (slow-controlled respiration), and 3 minutes of controlled respiration at 0.33 Hz (fast-controlled respiration). The frequency of maximum coherence (above the arbitrary threshold of 0.5) of BP and RR interval variabilities was searched between 0.033-0.133 Hz and 0.200-0.400 Hz to obtain baroreflex gain and phase shift in low and high frequency bands, respectively. Mean phase shifts of -79.1 and -67.0 degrees (-2.4 and -2.1 s) were found during slow-controlled respiration in the supine and sitting body positions, respectively. The mean phase shift between systolic BP and RR interval in the low frequency band was found between 83 and -109 degrees for body positions and respiration regimes. The actual baroreflex related time lag between systolic BP and RR variations was found between 3.5 and 5.1 seconds. The study concludes that the appropriate, and not always easy, selection of the frequency of maximum coherence between BP and HR oscillation is crucial for an accurate cross-spectral assessment of baroreflex sensitivity.

[Function and dysfunction of the endothelium]. / Funkce a dysfunkce endotelu.

Endothelium is a multi-functional barrier separating blood from interstitium. It plays a role in coagulation, inflammation, angiogenesis and it has vasomotor functions. The endothelial dysfunction can be considered as an initial stage of atherosclerosis. Using morphological and biochemical methods it is possible to study the influence of cardiovascular risk factors on the vessels and the effect of therapeutic interventions. A short review of endothelial functions, endothelial dysfunction and its quantification methods is presented in this article.

Stability of the noninvasive baroreflex sensitivity assessment using cross-spectral analysis of heart rate and arterial blood pressure variabilities.

BACKGROUND: Depressed baroreflex sensitivity (BRS), usually estimated using the invasive phenylephrine method or the nitroprusside test, is significantly and independently associated with an increased risk of malignant ventricular arrhythmias and sudden cardiac death in patients surviving acute myocardial infarction. Several investigators have compared the standard phenylephrine test and different noninvasive methods. HYPOTHESIS: This study evaluated the influence of different body positions with different breathing regimes on cross-spectral baroreflex indices (coherence between the spectral densities of blood pressure and cardiac cycle variabilities) in both low- and high-frequency bands. METHODS: The data were obtained in 103 patients (73 males, aged 53 +/- 12 years) with coronary artery disease and/or hypertension. Simultaneous electrocardiographic and noninvasive blood pressure recordings were obtained in each subject in both supine and sitting positions during both spontaneous and slow and fast controlled respiration (0.1 and 0.33 Hz). RESULTS: The results show a significant bias and disagreement between noninvasive baroreflex sensitivity (BRS) indices. The mean values of the baroreflex in low frequency ranged from 5.0 +/- 5.3 to 10.1 +/- 7.9 ms/mmHg, while in high frequency, the mean values ranged from 6.6 +/- 6.1 to 10.1 +/- 7.9 ms/mmHg. The limits of agreement ranged from +/-1.7 to +/-4.1 ms/mmHg with bias from -1.0 to +0.7 ms/mmHg. CONCLUSION: A comprehensive comparison of different methods shows that BRS estimated in low-frequency band in sitting position during spontaneous respiration is the most representative part of the global baroreflex gain.