Monitoring of Cardiorespiratory Parameters in Rats-Validation Based on Pharmacological Stimulation.

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.

Blood Pressure Control and Antihypertensive Treatment among Hemodialysis Patients-Retrospective Single Center Experience.

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.

Individual variability of vascularization of the anterior papillary muscle within the right ventricle of human heart.

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.

The structure of the vascular system of the septomarginal trabecula in the heart of an adult.

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.

Promising effects of xanthine oxidase inhibition by allopurinol on autonomic heart regulation estimated by heart rate variability (HRV) analysis in rats exposed to hypoxia and hyperoxia.

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.