Total Peripheral Vascular Resistance Research Articles

How the Deuteration of Dronedarone Can Modify Its Cardiovascular Profile: In Vivo Characterization of Electropharmacological Effects of Poyendarone, a Deuterated Analogue of Dronedarone.

Since deuterium replacement has a potential to modulate pharmacodynamics, pharmacokinetics and toxicity, we developed deuterated dronedarone; poyendarone, and assessed its cardiovascular effects. Poyendarone hydrochloride in doses of 0.3 and 3mg/kg over 30s was intravenously administered to the halothane-anesthetized dogs (n = 4), which provided peak plasma concentrations of 108 ± 10 and 1120 ± 285ng/mL, respectively. The 0.3mg/kg shortened the ventricular repolarization period. The 3mg/kg transiently increased the heart rate at 5min but decreased at 45min, and elevated the total peripheral vascular resistance and left ventricular preload, whereas it reduced the mean blood pressure at 5min, left ventricular contractility and cardiac output. The transient tachycardic action is considered to be induced by the hypotension-induced, reflex-mediated increase of sympathetic tone. The 3mg/kg delayed both intra-atrial and intra-ventricular conductions, indicating Na+ channel inhibitory action. Moreover, the 3mg/kg transiently shortened the ventricular repolarization period at 5min. No significant change was detected in the late repolarization by poyendarone, indicating it might not hardly significantly alter rapidly activating delayed-rectifier K+ current (IKr). Poyendarone prolonged the atrial effective refractory period greater than the ventricular parameter. When compared with dronedarone, poyendarone showed similar pharmacokinetics of dronedarone, but reduced β-adrenoceptor blocking activity as well as the cardio-suppressive effect. Poyendarone failed to inhibit IKr and showed higher atrial selectivity in prolonging the effective refractory period of atrium versus ventricle. Thus, the deuteration may be an effective way to improve the cardiovascular profile of dronedarone. Poyendarone is a promising anti-atrial fibrillatory drug candidate.

Glucose reduces the osmopressor response in connection with the tyrosine phosphorylation of focal adhesion kinase in red blood cells.

Glucose ingestion attenuates the water ingestion-induced increase in the total peripheral vascular resistance and orthostatic tolerance. We investigated the gastrointestinal physiology of glucose by examining the effect of glucose ingestion on the functional expression of focal adhesion kinase (FAK) in red blood cell (RBC) membrane. This study was performed in 24 young, healthy subjects. Blood samples were collected at 5 min before and 25 min and 50 min after an ingestion of 10% glucose water 500 mL, water 500 mL, or normal saline 500 mL. We determined glucose and osmolality in plasma, and phosphorylation of aquaporin 1 (AQP1), glucose transporter 1 (Glut1), and FAK in RBC membrane. Our results showed that glucose ingestion reduced the rise of peripheral vascular resistance after water ingestion and upregulated the serine phosphorylation of Glut1. It also lowered both the serine phosphorylation of FAK and tyrosine phosphorylation of AQP1, compared with the ingestion of either water or saline. In an ex vivo experiment, glucose activated the Glut1 receptor and subsequently reduced the expression of FAK compared with 0.8% saline alone. We concluded that glucose activates Glut1 and subsequently lowers the functional expression of FAK, a cytoskeleton protein of RBCs. The functional change in the RBC membrane proteins in connection with the attenuation of osmopressor response may elucidate the pathophysiology of glucose in postprandial hypotension.

ВЛИЯНИЕ ДЖЕМА ИЗ ПЛОДОВ АЛЫЧИ С ВЫСОКИМ СОДЕРЖАНИЕМ БИОЛОГИЧЕСКИ АКТИВНЫХ ВЕЩЕСТВ НА СОСТОЯНИЕ ЗДОРОВЬЯ ПОДРОСТКОВ. ВОСПРОИЗВОДИМОСТЬ РЕЗУЛЬТАТОВ

The goal is to study the effect of jam from cherry plum with a high content of biologically active substances on the health of adolescents and to establish the reproducibility of the effect obtained. Methods. 62 teenagers (pupils of the 7th and 8th grades of the school) were examined, the average age was 13.02±0.71 years old, boys – 36 (58.1 %), girls – 26 (41.9 %). A part of teenagers at school daily for 15 days received 30 g of cherry plum jam containing high concentrations of flavonoids (anthocyanins, leucoanthocyanins), pectins, vitamins (ascorbic acid), macro- and microelements (potassium, copper, zinc, iron, etc.). The state of the circulatory and respiratory organs, the psychomotor properties of the nervous system (NS) and the mental performance of adolescents has been studied. Results. The achieved values of indicators in adolescents who used and did not use cherry plum in the 1st and 2nd year of the study are compared. In the first year of the study, adolescents who used jam showed achievement of optimal values of arterial pressure, stroke volume of the heart and minute volume of blood circulation, total peripheral vascular resistance, peak expiratory flow rate, average rate of tapping test tapping and of the nervous system lability compared to adolescents, not using jam. Similar achievements in the health status of adolescents who used cherry plum jam were recorded in the 2nd year of the study, but less pronounced. Conclusions. The use of cherry plum with a high content of biologically active substances as an additional food leads to improved physical health, psychomotor properties of the nervous system and mental health of adolescents. The resulting healing effect of the use of jam from the fruit of cherry plum is replicable in subsequent studies.

Impact of winter savory essential oil on the functioning of cardiovascular system of the elderly

Objective. To study the effects of winter savory essential oil on the functioning of cardiovascular system of the elderly. Materials and methods. The study includes 97 women of older age with increased systolic blood pressure, which were divided into control (session of relaxation therapy only), and experimental (session of relaxation therapy combined with aromatherapy of winter savory essential oil) groups. Before and after the sessions, systolic and diastolic blood pressure, heart rate of the testees were measured and the following indices were determined: pulse blood pressure, minute blood volume, mean dynamic blood pressure, total peripheral vascular resistance, heart index, systolic index, Robinson index, Kerdo index, circulatory efficiency coefficient. Results. The study found that the use of winter savory essential oil led to a significant decrease in systolic blood pressure (exposure for 10 and 30 minutes) and heart rate (all time periods). The values of pulse and average dynamic blood pressure significantly decreased during aromatherapy for 10 or 30 minutes, there was also a significant decrease in the values of minute blood volume after 10 and 30-minute session of aromarelaxation. After 30-minute aromarelaxation there was an increase in the total peripheral vascular resistance. The change of Kerdo index value in the direction of parasympathetic after 30 minutes of aromatherapy was revealed. The value of the coefficient of efficiency of blood circulation significantly decreased after 10 and 30 minutes of aromarelaxation, Robinson index decreased during all time periods of exposure. Conclusion. On the basis of the obtained data, it can be concluded that the essential oil of winter savory has a pronounced normalizing effect on the circulatory function of the elderly women with systolic hypertension.

Features of changes in volume-impedance hemodynamic indicators during the tilt test in young males with a history of vasovagal syncopes

The direction of changes in hemodynamic parameters during the tilt test (TT) nin individuals with history of vasovagal syncope (VVS) is a subject of discussion. to study changes of volume-impedance hemodynamic indicators in the process of tilt test in somatically healthy young men with history of VVS. A total of 102 men aged 18-30 years were divided into 4 groups, taking into account the specific features of fainting history and response to TT. Persons of group 1 (n=14) had history of VVS and positive response to TT (syncope). Subjects of group 2 (n=14) had history of VVS and a pattern of postural tachycardia without fainting during TT. Persons of group 3 (n=42) had history of VVS and negative response to TT. Subjects of group 4 (n=32) had no history of VVS and negative response to TT. During TT, we studied dynamics of some indicators, including cardiac output (CO) and total peripheral vascular resistance (TPVR). In individuals of all groups in the initial horizontal phase of TT values of CO and TPVR corresponded to the norm. Subjects of group 1 had significantly lower CO compared with subjects of groups 2, 3, 4 (p<0.05, p<0.01, p<0.05, respectively). Values of TPVR in subjects of group 1 were significantly higher than in subjects of groups 2, 3, 4 (p<0.05; p<0.05; p<0.05, respectively). In response to orthostasis CO values increased in groups 1, 2, 4 (by 18%, 10%, 5%, respectively) and did not change in group 3; TPVR values decreased in groups 1, 2 (by 8%, 0.5%, respectively), and increased in groups 3, 4 (by 8%, 4% respectively). In the final horizontal phase of TT, CO values in group 1 were significantly lower than in groups 3, 4 (p<0.05), while TPVR values did not significantly differ between all groups (p>0.05). In tilt-positive and tilt-negative subjects with history of VVS, standardized postural stress leads to unidirectional changes in cardiac output, but to multidirectional changes in total peripheral vascular resistance.

Development of basic criteria for assessing the adaptation level of athletes-mountaineers’ organism to a mountain climate

Introduction. Mountain climbers’ activity is constantly accompanied by harsh ambient conditions. Changeable exogenous factors joint by reduced oxygen pressure considerably complicate athletes’ medical support and demand objective appraisal elaboration for the purpose of adaptation level timely correction. Aim. To develop the athletes’ body adaptation level’s criteria under extreme conditions of sport work. Materials and methods . Mathematical-statistical analysis of results of examenation of 62 climbers at the age of 30.5±3.6 years old was carried out using volumetric compression oscillometry method before, during and after sporting event. Results. As a result of the obtained data of volumetric compression oscillometry indicators’ analysis, mountain climbers were divided into three groups of kinetic blood circulation types, which were hypokinetic, eukinetic and hyperkinetic. Climbers with hyperkinetic blood type were not admitted to take part in sporting event. Statistically significant (p<0.05) signs allowing to determine athlete’s organism adaptation level to external environment exogenous factors were specified. These features are diastolic blood pressure, lateral systolic blood pressure, average hemodynamic arterial pressure, arterial pulse pressure, energy consumption indicators for the movement of one liter of blood, total peripheral vascular resistance, specific peripheral vascular resistance, systolic pressure and linear circulation time. Conclusion. The analysis of volumetric compression oscillometry revealed significant (p<0.05) criteria for evaluating the level of adaptation, where the change of adaptation level from the optimum condition to the violation of the regulation mechanisms of the organism was accompanied by an increase in myocardial contractility, heart rate, blood pressure, minute volume of blood flow and a decrease in stroke volume. These changes were confirmed by the transition to a more energy-intensive type of regulation of blood circulation at rest. Correlation between the increased intensity of the training process in the conditions of mountain climate and the increase of long-term hemodynamics was found, and the lack of timely correction of the adaptation level of organism contributed to the increase in infectious morbidity.

Mechanism of Thiazide Diuretic Arterial Pressure Reduction: The Search Continues.

Thiazide diuretic (TZD)-mediated chronic reduction of arterial pressure is thought to occur through decreased total peripheral vascular resistance. Further, the decreased peripheral vascular resistance is accomplished through TZD activation of an extrarenal target, resulting in inhibition of vascular constriction. However, despite greater than five decades of investigation, little progress has been made into the identification of the TZD extrarenal target. Proposed mechanisms range from direct inhibition of constrictor and activation of relaxant signaling pathways in the vascular smooth muscle to indirect inhibition through decreased neurogenic and hormonal regulatory pathways. Surprisingly, particularly in view of this lack of progress, comprehensive reviews of the subject are absent. Moreover, even though it is well recognized that 1) several types of hypertension are insensitive to TZD reduction of arterial pressure and, further, TZD fail to reduce arterial pressure in normotensive subjects and animals, and 2) different mechanisms underlie acute and chronic TZD, findings derived from these models and parameters remain largely undifferentiated. This review 1) comprehensively describes findings associated with TZD reduction of arterial pressure; 2) differentiates between observations in TZD-sensitive and TZD-insensitive hypertension, normotensive subjects/animals, and acute and chronic effects of TZD; 3) critically evaluates proposed TZD extrarenal targets; 4) proposes guiding parameters for relevant investigations into extrarenal TZD target identification; and 5) proposes a working model for TZD chronic reduction of arterial pressure through vascular dilation.

Is it possible to augment myocardial protection during cardiopulmonary bypass by administration of inhalational anesthetics?

Aim: To evaluate the possibility to augment myocardial protection with desflurane and sevoflurane by prolongation of their delivery into the oxygenator of the cardiopulmonary bypass (CPB) pump during surgical myocardial revascularization.Materials and methods: This randomized prospective study included 75 patients with ischemic heart disease who underwent aortocoronary and mammary coronary bypass grafting with extracorporeal circulation from 2014 to 2017. The patients were allocated into the three study group by means of a random number table generated by Statistica 10.0 software, depending on the anesthetic agent used: group 1, desflurane (n=30), group 2, sevoflurane (n=28), and group 3 (control), propofol (n=17). Desflurane and sevoflurane were delivered into the oxygenator during the artificial circulation. Hemodynamic parameters were assessed, such as cardiac index, total peripheral vascular resistance index, pulmonary artery wedge pressure. Changes in lactate, pyruvate, alanine, glutamate, glutamine, aspartate, asparagine, taurine, leucine, isoleucine and valine levels over time were assessed in blood taken from the heart coronary sinus before aortal clamping, before release of the clamp and after 30 minutes of reperfusion. During the first 24 hours post perfusion, we assessed the incidence of postperfusion heart failure (PPHF), duration of mechanical ventilation and duration of stay in the intensive care unit. Troponin I levels were measured at 12 and 24 hours after the intervention.Results: There were no significant differences in the changes of the hemodynamic parameters over time in all the groups. The PPHF incidence and the course of the postoperative period were similar in all the groups. Irrespective on the type of the anesthesia, lactate and pyruvate levels increased during the CPB, with no significant differences between the groups, as well as the postoperative troponin I levels at 12 and 24 hours after surgery. No differences between the groups were found for the changes of amino acid levels over time, except a significant reduction of alanine levels during the aortal clamp in the group 3.Conclusion: Prolongation of desflurane and sevoflurane delivery into the CPB pump oxygenator does not augment myocardial protection during myocardial revascularization surgery.

Vascular-ventricular coupling during exercise is not affected by exaggerated blood pressures in endurance-trained athletes.

This study sought to examine whether cardiovascular performance during exercise, assessed using the vascular-ventricular coupling index (VVC), was affected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. Subjects were middle-aged endurance-trained men and women. Blood pressure measurements and left ventricular echocardiography were performed in a semiupright position at rest and during steady-state cycling at workloads that elicited 100-110 beats/min (stage 1) and 130-140 beats/min (stage 2). These data were used to calculate effective arterial elastance index (EaI), left ventricular end-systolic elastance index (ELVI), and their ratio (VVC). Additional measurements of left ventricular volumes and function (i.e., stroke volume, cardiac output, and longitudinal strain) and indirect assessments of peripheral vascular function (i.e., total arterial compliance and peripheral vascular resistance) were examined. Fourteen subjects with EBP (EBP+, 50% men) and 14 sex-matched subjects without EBP (EBP-) participated, with results presented as EBP+ versus EBP-. EaI and ELVI increased from rest to exercise while VVC decreased, but only ELVI was different between groups at stage 1 [7.6 (1.8) vs. 6.4 (1.0) mmHg·ml-1·m-2, P = 0.045] and stage 2 [10.3 (1.6) vs. 8.0 (1.7) mmHg·ml-1·m-2, P < 0.001]. Additional comparisons revealed no group difference in the contribution of the Frank-Starling mechanism or left ventricular and peripheral vascular function during exercise. The cardiovascular adjustment to exercise in athletes with EBP is achieved through a matched increase in both EaI and ELVI, and the absence of between-group differences in left ventricular or peripheral vascular function suggests that other factors may contribute to the EBP response.NEW & NOTEWORTHY Cardiovascular performance during submaximal exercise, assessed using vascular-ventricular coupling, is unaffected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. The underlying mechanisms of EBP in athletes remain unknown as changes in left ventricular and peripheral vascular function during exercise were similar in athletes with and without EBP.

The benefits of a challenge approach on match day: Investigating cardiovascular reactivity in professional academy soccer players

This study assessed physiological (cardiovascular) and psychological (confidence, control, and approach focus) data in professional academy soccer players prior to performance in competitive matches. A challenge state is characterised by an increase in cardiac output (CO), and a decrease in total peripheral vascular resistance (TPR). Data were collected from 37 participants, with 19 of these providing data on two separate occasions. Performance was measured using coach and player self-ratings. Challenge reactivity was positively, and significantly, associated with performance. Participants who demonstrated blunted cardiovascular (CV) responses performed significantly worse than participants who displayed either challenge or threat reactivity. There was mixed consistency in CV reactivity for those participants whose data were collected on more than one occasion, suggesting that some participants responded differently across the competitive matches. The association between self-report data and CV responses was weak. This study supports previous research demonstrating that challenge reactivity is associated with superior performance.

Hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome

To explore the hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome (POTS) and to compare hemodynamic parameters of POTS patients with decreased cardiac index (CI) and those with not-decreased CI. A retrospective study was conducted to show the trends of CI, total peripheral vascular resistance index (TPVRI), heart rate and blood pressure in standing-up test of 26 POTS patients and 12 healthy controls, and to compare them between the two groups. The POTS patients were divided into two groups based on CI decreasing or not in standing-up test, namely decreased CI group (14 cases) and not-decreased CI group (12 cases). The trends of the above mentioned hemodynamic parameters in standing-up test were observed and compared between decreased CI group and not-decreased CI group. In standing-up test for all the POTS patients, CI (F=6.936, P=0.001) and systolic blood pressure (F=6.049, P<0.001) both decreased significantly, and heart rate increased obviously (F=113.926, P<0.001). However, TPVRI (F=2.031, P=0.138) and diastolic blood pressure (F=2.018, P=0.113) had no significant changes. For healthy controls, CI (F=3.646, P=0.016), heart rate (F=43.970, P<0.001), systolic blood pressure (F=4.043, P=0.020) and diastolic blood pressure (F=8.627, P<0.001) all increased significantly in standing-up test. TPVRI (F=1.688, P=0.190) did not change obviously. The changing trends of CI (F=6.221, P=0.001), heart rate (F=6.203, P<0.001) and systolic blood pressure (F=7.946, P<0.001) over time were significantly different between the patients and healthy controls, however, no difference was found in TPVRI and diastolic blood pressure (P > 0.05). Among the POTS patients, CI was significantly different between decreased CI group and not-decreased CI group (F=14.723, P<0.001). Systolic blood pressure of the former decreased obviously (F=8.010, P<0.001), but it did not change obviously in the latter (F=0.612, P=0.639). Furthermore, none of the changes of TPVRI, heart rate and diastolic blood pressure in standing-up test were significantly different between the two groups (P > 0.05). Age was an independent factor for decreased CI patients (P=0.013, OR=2.233; 95% CI, 1.183 to 4.216). POTS patients experience vital hemodynamic changes in standing-up test, part of them suffering from decreased CI, but others from not-decreased CI. Age is an independent factor for patients suffering from decreased CI.

Potentiation of general multimodal anesthesia by contact laser effects on the body in the red range in patients with lower limb high amputations

Objective. The aim of the study is to develop a technique of potentiating traditional multimodal anesthesia with contact laser exposure to the body in the red range (650 nm) in patients with critical lower limb ischemia (CLI).Materials and methods. Multimodal anesthesia in the main group was performed with the potentiation of modern laser technology in 70 to 94 years old 35 patients [7 (20.0 %) women and 28 (80.0 %) men] with CLI and associated diseases. As a comparison group, a retrospective group of 23 patients was selected who underwent a high amputation of the lower extremities without potentiation of multimodal anesthesia with laser blood radiation. Multimodal anesthesia was additionally potentiated with quantum hemotherapy sessions. Sessions were carried out using a fifth-generation semiconductor contact laser irradiation of blood LASPOT (PRC) in the form of a wristwatch with an additional effect on the acupuncture points Nei-Guan, Tun-li – the heart meridian, connection with the inner world, Ling-dao – the meridian hearts, the road of the spirit. The first session was performed to patients before surgery — a duration of 15 minutes; the second — during surgery — a duration of 30 minutes.Results. The obtained data on the shifts of peripheral hemodynamic parameters at the stages of surgical interventions in patients of both groups practically did not demonstrate significant differences from the baseline values, reflecting the adequacy of the degree of anesthesiological protection. In patients of the main group, central hemodynamic indices: the cardiac index (CI) significantly increased from 2.81 ± 0.49 to 3.15 ± 0.58 (p &lt; 0.05) l/min∙m2, and total peripheral vascular resistance (TPVR) decreased from 1587.5 ± 494.3 to 1492.7 ± 427.8 dyn∙s∙cm-5. In patients of the comparison group, CI increased during surgery from 2.83 ± 0.53 to 3.02 ± 0.35 l/min∙m2, and at the end of the operation it returned to baseline. Potentiation of multimodal anesthesia with modern laser technologies in patients of the main group made it possible to reduce during surgical interventions the average dose of fentanyl, which was 0.98 ± 0.12 mcg/kg/h, while in patients of the comparison group, the consumption of fentanyl was 3.28 ± 0.18 mcg/kg/h (with traditional combined general anesthesia, the flow rate of fentanyl during surgery is on average 5–12 mcg/kg/h or more).Conclusion. The method of potentiation of the traditional scheme of general combined anesthesia with optical radiation of the red range (650 nm) allows to achieve more pronounced effects of hemodynamic control, makes it possible to reduce the dose of fentanyl, reduce the pharmacological load on the operated patient.

Recovery Time Profiling After Short-, Middle- and Long-Distance Swimming Performance.

Piras, A, Cortesi, M, Campa, F, Perazzolo, M, and Gatta, G. Recovery time profiling after short-, middle- and long-distance swimming performance. J Strength Cond Res 33(5): 1408-1415, 2019-We investigated cardiac autonomic responses and hemodynamic parameters on recovery time after short-, middle- and long-swimming performance. Ten male regional-level swimmers were tested to estimate time and frequency domains of arterial baroreflex sensitivity (BRS) and heart rate variability after 100, 200, and 400 m of front crawl. We found a BRS reduction for 90 minutes after a maximal 100- and 200-m front crawl event, meanwhile the reflex was restored back to the baseline value approximately 70 minutes after 400 m. The vagally mediated high-frequency power of R-R intervals was significantly reduced for 30 minutes after 400 m, and more than 90 minutes after 100 and 200 m, with a concomitant increase of sympathetic modulation. After 400 m, athletes have reduced their stroke volume for 50 minutes, which remained at the baseline level after 100 and 200 m. Heart rate was restored back after 90 minutes in all conditions, whereas total peripheral vascular resistance was significantly reduced for 50 minutes after 200 and 400 m, with a persistent reduction after 100 m. Time course of autonomic recovery after 3 different swimming performances is influenced by exercise intensity and duration, showing a rapid recovery after 400 m, an intermediate recovery after 200 m, and a significantly delayed recovery after a more strictly anaerobic performance like 100 m of front crawl. These results could encourage coaches to consider that athlete might be affected by the specific recovery time of the previous exercise performed, suggesting that the management of the exercise intensity, and appropriate monitoring of cardiac autonomic parameters might be helpful to know the physical condition of each athlete.

EFFECT OF PROPRANOLOL ON AEROBIC-HEMODYNAMIC SUPPORT OF PHYSICAL ACTIVITY IN PATIENTS WITH EFFORT ANGINA, POSITIVE ANTIANGINAL ACTION AND THE ABSENCE OF CLINICAL EFFECT AFTER PROPRANOLOL-BASED TREATMENT

Aim. To analyze the changes in the aerobic-hemodynamic parameters during physical exercise in patients with effort angina administered with reference non-selective beta-blocker propranolol (Obsidan) with positive antianginal action and the absence of clinical effect after the drug intake.Material and Methods. A total of 58 patients (mean age of 54.2 [48.5; 59.5] years) with effort angina of functional class II–IV were examined with spiro-veloergometry tests before and after administration of propranolol (Obsidan: manufactured by Isis Pharma GmbH, Germany) at a dose of 40 mg. At threshold physical activity the following parameters were assessed: oxygen consumption (VO2 ), specific oxygen consumption, cardiac index (CI), rate pressure product (RPP); total peripheral vascular resistance (TPVR), arteriovenous oxygen difference (a-vDО2 ) and mechanical work of the heart (HW).Results. The efficacy of single-dose obsidian was observed in 58.6% of patients with angina (group 1); in this, tolerance to physical exercise increased from 50.0 [25.0; 75.0] W to 75.0 [50.0; 100.0] W. In the rest of patients (group 2), no antianginal effect was registered. At the first stage (at initial threshold physical activity level), administration of propranolol was characterized by saving pattern of heart function: statistically significant decrease in the heart rate, mean arterial pressure, CI and HW. This naturally resulted in reduction of myocardial oxygen demand (decrease in RPP from 163.0 [134.5; 218.5] U to 102.0 [90.0; 142.5] U; p&lt;0.001) and predetermined the drug anti-ischemic action. At the second stage (maximum physical effort), an increase in the physical activity, caused by increase in VO2 from 738.0 [604.5; 1148.0] mL/min to 972.0 [774.5; 1458.0] mL/min, occurred due to higher oxygen extraction from peripheral blood (a-vDО2 increase; p&lt;0.002). In group 2, despite the absence of an increase in tolerance to physical exercise, administration of propranolol was characterized by low RPP threshold i.e. the physical effort similar to the initial level was performed at a lower cardiac energy consumption.Conclusion. Therefore, anti-ischemic effect of Obsidan was due to a decrease in theenergy expenditure of the cardiac function along with a limitation in the hemodynamic productivity efficiently compensated by an increase in the oxygen extraction from circulating blood during physical activity.

EFFECT OF PROPRANOLOL ON AEROBIC-HEMODYNAMIC SUPPORT OF PHYSICAL ACTIVITY IN PATIENTS WITH EFFORT ANGINA, POSITIVE ANTIANGINAL ACTION AND THE ABSENCE OF CLINICAL EFFECT AFTER PROPRANOLOL-BASED TREATMENT

Aim. To analyze the changes in the aerobic-hemodynamic parameters during physical exercise in patients with effort angina administered with reference non-selective beta-blocker propranolol (Obsidan) with positive antianginal action and the absence of clinical effect after the drug intake.Material and Methods. A total of 58 patients (mean age of 54.2 [48.5; 59.5] years) with effort angina of functional class II–IV were examined with spiro-veloergometry tests before and after administration of propranolol (Obsidan: manufactured by Isis Pharma GmbH, Germany) at a dose of 40 mg. At threshold physical activity the following parameters were assessed: oxygen consumption (VO2 ), specific oxygen consumption, cardiac index (CI), rate pressure product (RPP); total peripheral vascular resistance (TPVR), arteriovenous oxygen difference (a-vDО2 ) and mechanical work of the heart (HW).Results. The efficacy of single-dose obsidian was observed in 58.6% of patients with angina (group 1); in this, tolerance to physical exercise increased from 50.0 [25.0; 75.0] W to 75.0 [50.0; 100.0] W. In the rest of patients (group 2), no antianginal effect was registered. At the first stage (at initial threshold physical activity level), administration of propranolol was characterized by saving pattern of heart function: statistically significant decrease in the heart rate, mean arterial pressure, CI and HW. This naturally resulted in reduction of myocardial oxygen demand (decrease in RPP from 163.0 [134.5; 218.5] U to 102.0 [90.0; 142.5] U; p&lt;0.001) and predetermined the drug anti-ischemic action. At the second stage (maximum physical effort), an increase in the physical activity, caused by increase in VO2 from 738.0 [604.5; 1148.0] mL/min to 972.0 [774.5; 1458.0] mL/min, occurred due to higher oxygen extraction from peripheral blood (a-vDО2 increase; p&lt;0.002). In group 2, despite the absence of an increase in tolerance to physical exercise, administration of propranolol was characterized by low RPP threshold i.e. the physical effort similar to the initial level was performed at a lower cardiac energy consumption.Conclusion. Therefore, anti-ischemic effect of Obsidan was due to a decrease in theenergy expenditure of the cardiac function along with a limitation in the hemodynamic productivity efficiently compensated by an increase in the oxygen extraction from circulating blood during physical activity.

Renal Microvascular Rarefaction Accompanies Interstitial Fibrosis and Tubular Damage in One Kidney‐Deoxycorticosterone Acetate‐Salt (1K/DOCA/salt)‐Dependent Hypertension

High dietary salt intake is a risk factor for hypertension and chronic kidney disease. However, the mechanisms involved remain poorly understood. Microvascular rarefaction ‐ defined as the loss of arterioles and capillaries within a tissue ‐ has the potential to increase total peripheral vascular resistance and cause local hypoxia and tissue damage. Here we utilised one kidney‐deoxycorticosterone acetate‐salt (1K/DOCA/salt)‐treated mice to investigate whether the development of hypertension and renal damage are associated with microvascular rarefaction. C57BL6/J mice were uninephrectomised and treated for 21 d with DOCA (2.4 mg/day, s.c.) and 0.9% NaCl in the drinking water. Normotensive controls were uninephrectomized and received a placebo pellet and normal drinking water (1K/placebo). Blood pressure (BP) was measured via tail cuff; renal vascular density was assessed immunohistochemically as the percentage area of CD31‐positive staining; renal collagen was detected with picrosirius red; and hematoxylin and eosin were used to visualise renal inflammation and histopathology. 1K/DOCA/salt‐treated mice had higher BPs (160±4 vs. 126±4 mmHg; n≥7; P≤0.0001) and renal weights (321±16 vs. 251±13 mg; n≥7; P&lt;0.05) than 1K/placebo mice. 1K/DOCA/salt‐treated mice also displayed marked renal fibrosis, inflammation and damage as evidenced by a 10‐fold increase in interstitial collagen (n≥7; P&lt;0.05), the presence of inflammatory cells, tubular dilatation and atrophy, and a loss of epithelial brush borders. Importantly, 1K/DOCA/salt‐treatment was associated with a 50% reduction in microvascular density (n≥7; P&lt;0.05), mainly due to a loss of peritubular capillaries. Correlation analyses revealed a trend for an inverse association of peritubular capillary density with collagen deposition (n≥7; r= −0.7058; P= 0.117), but not with BP or inflammatory cell infiltration. Low magnification analysis of kidney sections revealed that peritubular capillary loss occurred in bands emanating from the arcuate arteries. Moreover, collagen deposition, inflammatory cell infiltration and tubular atrophy displayed a similar banding pattern. In summary, these studies reveal a likely association between microvascular rarefaction and fibrosis during the development of 1K/DOCA/salt‐dependent hypertension and renal damage. Future studies will assess whether strategies aimed at maintaining renal microvascular density can minimise renal fibrosis and damage.Support or Funding InformationThe work was funded by the National Health and Medical Research Council of Australia (GNT1143674)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Peculiarities of hemodynamic status of healthy newborns in early neonatal period

The study is devoted to the assessment of hemodynamic parameters in healthy newborns in the early neonatal period. The authors examined 76 healthy newborns aged up to 7 days. 12 (15.7%) of 76 children were diagnosed with intrauterine growth retardation of hypotrophic type and 14 children (18.49%) were premature. The authors evaluated the diameter of the outgoing tract of the left ventricle, pulmonary artery trunk, mitral and tricuspid valve rings. The disc method was used to determine the final diastolic volume of the left ventricle. The pulse Doppler was used to determine the integrated flow rate in the outflow tract of the left ventricle, the pulmonary artery trunk, on the mitral and tricuspid valves. After US there were calculated the stroke volume index, cardiac index, total peripheral vascular resistance and oxygen delivery index. The results. It integral flow rate was found to be a key indicator of central hemodynamics, which determines the magnitude of the stroke volume. Body weight and the presence of functioning fetal communications do not have a significant impact on the indexed systemic blood flow in healthy newborns. There is a direct correlation between the integral blood flow velocity and the stroke volume index, which is characteristic of all intracardiac anatomical structures.

Changes in parameters of hemodynamics in abdominal delivery with different methods of anesthesia

Aim. To study and evaluate changes in the basic parameters of central and peripheral hemodynamics of the maternal organs in caesarean section (CS) with different methods of anesthesia.Materials and methods. 127 pregnant women were divided into 4 subgroups: Ia (n=31) – general anesthesia (GA) using Ketamine, Ib (n=31) – GA with Sodium Thiopental, IIa (n=31) – spinal anesthesia (SA), IIb (n=34) – SA with Ondansetron 8 mg intravenous. The assessment was performed in 5 stages: 1 – initial; 2 – beginning of operation; 3 – fetal extraction; 4 – end of operation; 5 – 12 hours after operation. The main indicators of hemodynamics were analyzed: systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure, stroke volume of the heart (SV), cardiac output (CO), cardiac index (CI), total peripheral vascular resistance (TPR).Results. Maximum increase of SAP, DAP, MAP, CI, CO in GA groups was found at the prenatal stage. Decrease of SAP, DAP, MAP in SA groups was indicated. Hypotension in IIa subgroup required correction with Mesatone in 23 women, while only five patients from IIb subgroup had a correction of hypotension with Mesatone.Conclusion. In subgroups Ia and Ib, major changes were noted at the prenatal stage, which is manifested in energetically less favorable functioning of the cardiovascular system. CS with SA using Ondansetron was accompanied by favorable shifts at all the stages (especially at the prenatal stage), what is indicating hemodynamic safety of that method of anesthesia

Age-related features of central hemodynamics in sepsis. Article

Objective. To study the effect of the age of patients with sepsis on the level of central hemodynamic parameters (CHD) recorded in them upon admission to the intensive care unit and intensive care (ICU). Materials and methods. Retrospectively analyzed the survey data of 54 patients with sepsis diagnosed in accordance with the criteria of “Sepsis-3”. The age of patients was 22–83 (49.6 ± 2.17) years; the severity of the condition upon admission to ICU on the APACHE II scale of 6–19 (12.3 ± 0.47) points, on the SOFA scale — 4–14 (8 [6.10]) points. In patients with sepsis, a number of indicators characterizing the pumping function of the heart (cardiac function index (CFI), global ejection faction (GEF), cardiac power index (CPI), cardiac index (CI)) are inversely correlated with age, and the global end-diastolic volume Index (GEDI) — in direct connection. Results. In patients with sepsis, a number of CHD indicators had correlation with age: CFI — rho = −0.681 (p &lt; 0.0001), GEF — rho = −0.488 (p = 0.0002), CPI — rho = −0.438 (p = 0.0009), CI — rho = −0.395 (p = 0.0031) and GEDI — rho = 0.427 (p = 0.0013). Age &gt; 62 years was a predictor of CFI &lt; 4.5 min-1 (OR 1.1817, 95% CI 1.0642–1.3121; p &lt; 0.0001) and GEF &lt; 20 % (OR 1, 0741, 95% CI 1.0251-1.1255; p &lt; 0.0006). Age &gt; 64 years was a predictor of CI levels &lt; 2.5 L / min / m2 (OR 1.0834, 95% CI 1.0200-1.1508; p &lt; 0.0024). At the age of about 60, the likelihood of a decrease in heart rate and an increase in total peripheral vascular resistance also increased. Patients older than 62 years were more often diagnosed with concomitant hypertension (78 % and 12.5 %; p &lt; 0.001), coronary heart disease (64 % and 7.5 %; p &lt; 0.01) and post-infarction cardiosclerosis (7 % and 0 %; p = 0.02). Conclusion. The high probability of a decrease in the efficiency of the pumping function of the heart, as well as comorbidity for cardiovascular diseases, should be taken into account when choosing optimal measures for intensive treatment and monitoring in geriatric patients with sepsis.

The specificity of the antihypertensive action of the renin-angiotensin system inhibitors

Objective: the determination of the presence and character of action of the agents suppressing the renin-angiotensin system activity, their ability not only induce antihypertensive effect but also influence on the atherogenic blood potential and vascular remodeling in patients with arterial hypertension.Material and methods. 97 patients with stage 1 and 2 arterial hypertension were enrolled in the investigation. All patients were divided into 3 groups: 1) persons who were treated with receptor angiotensin II blockers 2) patients who were treated with ACE inhibitors (50 persons) 3) (control, 20 persons) patients who were treated with calcium channel blockers. All patients additionally received hydrochlorothiazide. The duration of the investigation was 1+0,1 year. There were measured the levels of SAP, DAP and pulse pressure. There was also determined the blood content of glucose, cholesterol, triglyceride, cholesterol of high-density lipoproteins with the use of analyzer BioSystems A‑25 (Spain). Level of low and very low density lipoprotein cholesterol was calculated according to the Freedwald formula. The echocardiographic investigation was carried out in M and B regimes according to the standard protocol. The cardiac activity, double product, total peripheral vascular resistance were calculated. The obtained data were analyzed statistically with the application of the program Excel 2003. The changes were considered as significant in р&lt;0,05. Results. The development of arterial hypertension was the result of functional and structural remodeling of the arterial vessels wall with an increase of total vascular resistance on the background of unchanged central hemodynamics in conjunction with the increase of cardiac activity and its demand in blood supply, which meant the decrease of the economy of heart activity. In parallel rose the blood atherogenic potential with increasing of the blood content of low and very low-density lipoprotein cholesterol, decreasing of high-density lipoprotein cholesterol and growth of atherogenic index. Application of calcium channel blockers with diuretics had pronounced antihypertensive effect but nevertheless, SAP pulse pressure and the level of total vascular resistance remained higher in comparison with normal values. That pointed only to the partial elimination of vascular remodelling. There was not also marked the influence on increased atherogenic potential. On the contrary, the application of renin-angiotensin system inhibitors led to the achievement of the target level of AP with a primary decrease of SAP and pulse pressure in conjunction with almost complete normalization of vascular resistance that witnessed about the pronounced regression of vascular remodeling. As a result, there was marked the significant decrease of the heart work and his blood supply demand, which pointed to the optimization of heart activity. There was also marked the significant decrease in blood atherogenic potential. Conclusions. The data proves the significant priority of the antihypertensive therapy with application of renin-angiotensin system inhibitors. That was proved by more pronounced AP normalization, more pronounced regression of the vascular remodelling, significant decrease of blood atherogenic potential and lowering as a result the risk of ischemic heart disease development.