Background and Objectives: Hypertension affects at least 80% of hemodialysis patients. Inappropriate control of blood pressure is mentioned as one of the essential cardiovascular risk factors associated with development of cardiovascular events in dialysis populations. The aim of the cross-sectional, retrospective study was the evaluation of the antihypertensive treatment schedule and control of blood pressure in relation to the guidelines in the group of hemodialysis patients. Additionally, we assessed the level of decrease in blood pressure by each group of hypotensive agents. Materials and Methods: 222 patients hemodialyzed in a single Dialysis Unit in three distinct periods of time—2006, 2011, and 2016—with a diagnosis of hypertension were enrolled in the study. The analysis of the antihypertensive treatment was based on the medical files and it consisted of a comparison of the mean blood pressure results reported during the six consecutive hemodialysis sessions. Results: The mean values of blood pressure before hemodialysis were as follows: 134/77, 130/74, and 140/76 mmHg, after hemodialysis 124/74, 126/73, and 139/77 mmHg in 2006, 2011, and 2016 respectively. The goal of predialysis blood pressure control (<140/90) was achieved by up to 64.3% of participants in 2006 as compared to 49.4% in 2016. Additionally, the postdialysis goal (<130/90) reached 57.1% of the study population in 2006 as compared to 27.1% of patients in 2016. The differences in percentage of patients using single, double, triple, and multidrug therapy during observation were not statistically significant. The most often used drugs were ß-blockers, diuretics, and calcium channel blockers in all points of the study. Blockades of the renin–angiotensin–aldosterone system in 2006 and calcium channel blockers in 2011 and 2016 were the drugs with highest impact on lowering blood pressure. Conclusions: The goal of predialysis or postdialysis blood pressure control was achieved in a lower percentage of patients during the period of the study. Blockade of renin–angiotensin–aldosterone system and calcium channel blockers decrease the blood pressure significantly. It is necessary to achieve better control of blood pressure in prevention of cardiovascular incidents.

The methods used in preclinical studies should minimize the suffering and the number of animals but still provide precise and consistent results enabling the introduction of drug candidates into the phase of clinical trials. Thus, we aimed to develop a method allowing us to perform preliminary safety and toxicity studies of candidates for human medicines, while reducing the number of animals. We have devised a method based on a combination of two devices: Plugsys (Transonics System Inc., Ithaca, NY, USA) and PhysioSuite (Kent Scientific Corporation, Torrington, CT, USA), which allow simultaneous registration of nine circulatory and respiratory parameters, and body temperature. Vehicle and adrenaline, or nitroglycerin, as reference substances were administered into the right femoral vein of Wistar rats. Physiological conditions were registered over 60 min after drug administration by measuring systolic, diastolic and mean blood pressure, heart rate (HR), blood perfusion of paw vessels, blood oxygen saturation, respiratory rate, average and peak exhaled CO2, and body temperature. Blood pressure was measured by cannula placed in the left common carotid artery and connected to the pressure transducer (Plugsys). The other parameters were measured by the PhysioSuite. Adrenaline-induced immediate dose-related hypertension and nitroglycerin hypotension were correlated with the change in blood perfusion. They both increased HR. Adrenaline decreased blood oxygen saturation and slightly affected respiratory parameters, while nitroglycerin caused a progressive increase in respiratory rate and a decrease in the peak of exhaled CO2. Our method may become an inseparable part of the preliminary safety and toxicity studies of tested drugs, while being an important step towards improving animal welfare.

L-carnitine which shuttles fatty acid into the mitochondria is known diet supplement used by athletes to improve physical performance. It is also used in supplementary treatment in cardiac insufficiency. Since effect of L-carnitine on cardiovascular regulation is unclear we investigated whether its prolonged supplementation would affect autonomic nervous system (ANS) control upon the heart in healthy elderly volunteers.Thirteen apparently healthy women aged 64 to 71 were supplemented in the double-blinded fashion with either 1.5 g of L-carnitine or placebo for 24 weeks. High resolution electrocardiogram was recorded before and after the supplementation. Time- and frequency-domain heart rate variability (HRV) analysis was performed to assess ANS control on the heart.Following L-carnitine supplementation the overall HRV represented by TSP or SDNN insignificantly decreased with a significant reduction of parasympathetic-related HRV indexes: rMSSD, HF and SD1. Consistently, a tendency towards an increase of indexes of sympathovagal balance: SDNN/rMSSD and SD2/SD1 may reflect vagal withdrawal. Reduction of autonomic control on the heart after L-carnitine chronic supplementation may be regarded as its adverse effect related to reported increased risk of severe cardiac events.

Regulatory synchronization between the heart and the arterial walls is essential for optimal blood delivery to tissues. We investigated functional coherence between heart rhythm and aortic wall compliance in 30 volunteers aged 65 – 74. ECG, carotid and iliac pulse-wave were recorded and digitized at 2 kHz. Carotid-femoral pulse-wave transit time (cfTT) which reflects aortic compliance was assessed using the intersecting tangent algorithm at time-point of the maximal upstroke of the second derivative of the filtered pulse signal. Time-series of 256 heart cycles were used for analysis of heart rate variability (HRV) and cfTT variability analysis. Averaged power spectral density (aPSD) was estimated within selected frequency ranges by fast Fourier transform (FFT) approach. Magnitude squared coherence (MSC) between the both spectra was estimated. All volunteers exhibited variable temporal patterns of both HRV and cfTT variability. aPSD was reduced along with decreasing of time-window from 60 to 240 s. High coherent states between HRV and cfTT variability were observed as a short time prominent MSC peaks in almost all participants. Individual patterns of irregular MSC changes in time but not a generalized model of its fluctuations seem to reflect dynamic functional interaction between the heart and aortic compliance at an advanced age.

Even trivial changing of body position from supine to sitting triggers complex cardiovascular adaptive response to prevent brain ischemiaThe study was performed to investigate heart rate asymmetry (HRA) and entropy-based heart rate variability (HRV) in stationary conditions in two body positions. Forty male students, aged 18-20 participated in this study. High resolution (4 kHz) ECG was recorded for 15 minutes; first in supine and after that in sitting position. 512 beat-to-beat interval (RRi) time-series were selected from each recording. Entropy-based parameters such as sample entropy (SampEn) and approximate entropy (ApEn) were computed. Heart cycles shorter (acceleration) or longer (deceleration) from the previous ones and sequential monotonic changes of RRi were also discriminated. Number of HR sequential runs significantly correlated with SampEn and ApEn both in sitting and supine position. Postural change from supine to sitting position resulted in a significant HR increase from 69 to 77 bpm. Both SampEn and ApEn were decreased after changing position (from 1.54 to 1.20 and from 1.23 to 1.08, respectively)Our data obtained from nonlinear HRV analysis indicate a reduction of cardiac control complexity following postural upright changing of body position.

Background.In cardiology, the paths of the arteries penetrating the septomarginal trabecula (SMT) are especially important.They provide blood supply to the apparatus of the right atrioventricular orifice and often form anastomoses with the system of the right coronary artery.Despite this, only a few publications discuss the morphological aspect of the septomarginal trabecula, and available histological analyses seldom deal with its blood supply.Objectives.The aim of this study was to analyze the vessel structure of the septomarginal trabecula in terms of the variability of the area of the cross-section of the lumen and the muscular layer of the artery. Material and methods.The study was carried out on the material of 50 human hearts from adults of both sexes.The material was divided into 4 morphological types.Histological examinations were conducted by means of classic staining methods.Results.At the initial cross-section of the septomarginal trabecula, the area of the cross-section increased to half of the length of the trabecula, and then it started to decrease.This is connected with the thickening of the inner muscular layer of the artery, which proportionally takes up more area of the cross-section of the whole artery of the SMT.The total area of the cross-section of all vessels in both types examined was also the largest in the middle part of the SMT.Furthermore, the results of this study confirm the presence of a connection between both systems of coronary arteries. Conclusions.As the septomarginal trabecula passes through the lumen of the right ventricle, its arteries become exposed to the influence of the factors which may evoke a biological response from the walls of this vessel, causing the thickening of the muscular layer and, as a result, of the section of the whole artery, in particular its middle part.

BACKGROUND:To date there is scarce published evidence reporting the dual blood supply reaching anterior papillary muscle (APM), which descends from both major coronary arteries. Such a vascular configuration can prevent the dysfunction of right ventricular entire valvular system in case of the occlusion of proximal part of either right coronary artery (RCA) or left coronary artery (LCA). The aim of our study was to determine the vascular pattern of APM blood supply which originates from two main coronary arteries, in the context of the APM and septomarginal trabecula (SMT) topography.METHODS:The study was carried out using tissue obtained from 36 human hearts. The material was divided into four morphological types of SMT/APM arrangement. Vascularization and blood supply pattern of papillary muscle was investigated following the analysis of multiple tissue cross sections. The origin of APM arterial supply was traced back to both main coronary arteries. Cross-sectional area of the arteries was estimated at the base of APM and compared within mixed male-female population, aged 18-76.RESULTS:We noted that as much as 78% of entire APM material had a blood supply vasculature originating from both LCA and RCA branches. In contrast, 22% of cases APM was supplied by a single coronary artery, while in each case it proved to be LCA. We have never found APM arterial supply provided exclusively by RCA. In case of double AMP blood supply an average of total cross-section area of the arteries branching from LCA, was noted to be in excess of two and a half times bigger in type III and more than two times bigger in type IV, as compared with the arteries originating from RCA.CONCLUSIONS:Our research confirm the possibility of double blood supply which vascularizes APM, but the finding does not necessarily apply in all cases. However, APM seems to be predominantly vascularized by arteries deriving from LCA, regardless of their morphological type.

BACKGROUND:It has long been suggested that reactive oxygen species (ROS) play a role in oxygen sensing via peripheral chemoreceptors, which would imply their involvement in chemoreflex activation and autonomic regulation of heart rate. We hypothesize that antioxidant affect neurogenic cardiovascular regulation through activation of chemoreflex which results in increased control of sympathetic mechanism regulating heart rhythm. Activity of xanthine oxidase (XO), which is among the major endogenous sources of ROS in the rat has been shown to increase during hypoxia promote oxidative stress. However, the mechanism of how XO inhibition affects neurogenic regulation of heart rhythm is still unclear.AIM:The study aimed to evaluate effects of allopurinol-driven inhibition of XO on autonomic heart regulation in rats exposed to hypoxia followed by hyperoxia, using heart rate variability (HRV) analysis.MATERIAL AND METHODS:16 conscious male Wistar rats (350 g): control-untreated (N = 8) and pretreated with Allopurinol-XO inhibitor (5 mg/kg, followed by 50 mg/kg), administered intraperitoneally (N = 8), were exposed to controlled hypobaric hypoxia (1h) in order to activate chemoreflex. The treatment was followed by 1h hyperoxia (chemoreflex suppression). Time-series of 1024 RR-intervals were extracted from 4kHz ECG recording for heart rate variability (HRV) analysis in order to calculate the following time-domain parameters: mean RR interval (RRi), SDNN (standard deviation of all normal NN intervals), rMSSD (square root of the mean of the squares of differences between adjacent NN intervals), frequency-domain parameters (FFT method): TSP (total spectral power) as well as low and high frequency band powers (LF and HF). At the end of experiment we used rat plasma to evaluate enzymatic activity of XO and markers of oxidative stress: protein carbonyl group and 8-isoprostane concentrations. Enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measures in erythrocyte lysates.RESULTS:Allopurinol reduced oxidative stress which was the result of hypoxia/hyperoxia, as shown by decreased 8-isoprostane plasma concentration. XO inhibition did not markedly influence HRV parameters in standard normoxia. However, during hypoxia, as well as hyperoxia, allopurinol administration resulted in a significant increase of autonomic control upon the heart as shown by increased SDNN and TSP, with an increased vagal contribution (increased rMSSD and HF), whereas sympathovagal indexes (LF/HF, SDNN/rMSSD) remained unchanged.CONCLUSIONS:Observed regulatory effects of XO inhibition did not confirm preliminary hypothesis which suggested that an antioxidant such as allopurinol might activate chemoreflex resulting in augmented sympathetic discharge to the heart. The HRV regulatory profile of XO inhibition observed during hypoxia as well as post-hypoxic hyperoxia corresponds to reported reduced risk of sudden cardiovascular events. Therefore our data provide a new argument for therapeutical use of allopurinol in hypoxic conditions.

Superoxide dismutase (SOD) is a crucial enzyme for endogenous oxidative balance. We tested how diethylthiocarbamate (DETC), a nonspecific SOD inhibitor and oxidant, influence heart rate variability (HRV). Fourteen Wistar rats (divided into two groups) with implanted subcutaneous ECG electrodes, maintained unrestrained in experimental setup. Time-series of 1024 RR intervals (RRi) were extracted from continuous ECG recording for HRV analysis. SOD activity was measured by dedicated assay kit. Intraperitoneal injection of DECT resulted in SOD inhibition by 30%. HRV analysis confirms a role of ROS in the regulation of sinoatrial rhythm. Increased HR after DETC injection was followed by a reduction in overall HRV including LF/HF. A significant reduction of the recurrence quantification analysis (RQA) parameters: %REC, %DET, DFAal and DFAa2 is indicative of some loss of complexity and self-similarity within the tested RRi time-series. The reduction of intrinsic harmonic correlations can be interpreted as a simplification of the regulatory feedback loops with more random heart rhythm poorly controlled by autonomic nervous system. Nonlinear dynamics methods such as RQA have a potential to increase the reliability of data in experimental studies.

Different approaches based on spectral and time-domain analysis of heart rate variability (HRV) were used to evaluate cardiac rhythm regulatory response to hypoxia. Nineteen male Wistar rats with previously implanted subcutaneous ECG electrodes, were maintained unrestrained in originally designed experimental setup, during normoxia and hypobaric hypoxia (-400 mmHg). RR intervals were extracted from continuous ECG recording. Time- and frequency-domain HRV estimates were computed from time-series of 1024 consecutive RRi. Power spectrum was obtained using both, fast Fourier transformation and autoregressive (AR) modeling. Compared to normoxia, hypoxia resulted in a significant increase of mean RRi, SDNN, rMSSD. AR and FFT analyses provided concordant power spectra across all tested bands. TP, including VLF, HF and predominantly LF, was increased in hypoxia, whereas LF/HF index of the sympatho-vagal balance remained unchanged. Changes in spectral power (TP, VLF, LF, HF) evoked by hypoxia correlated positively with simultaneous changes in SDNN and rMSSD. Interestingly, correlation coefficients derived from AR and FFT did not vary.

Subject of this study is the predictive value of baseline heart rate (HR) response to simulated diving. Twenty-seven male volunteers aged 20-25 performed apneic face immersion in cold water, while ECG was recorded. Both the initial HR increase and the following bradycardic response significantly correlated to resting HR. To optimally estimate the reference HR (mean HR or the longest 512-RR-interval-long time series or minimum of moving HR average at given lengths), we compared three different approaches, based on the best correlations between the evoked responses, HRV measures and resting baseline. Our data indicate lack of universal HR reference useful to predict resulting diving response. The longest RRi observed across preceding time window is apparently the best indicator of the diving bradycardic response, while the initial HR increase and time of voluntary apnea corresponds to the longtime HR average.