Decrease In Arterial Pressure Research Articles

Oscillations of Hemodynamic Parameters Induced by Negative Pressure Breathing in Healthy Humans.

INTRODUCTION: Negative pressure breathing is breathing with decreased pressure in the respiratory tract without lowering pressure acting on the torso. We lowered air pressure only during inspiration (NPBin). NPBin, used to increase venous return to the heart, is considered a countermeasure against redistribution of body fluids toward the head during spaceflight. We studied NPBin effects on circulation in healthy humans with an emphasis on NPBin-induced oscillations of hemodynamic parameters synchronous with breathing. We propose an approach to analyze the oscillations based on coherent averaging.METHODS: Eight men ages 24-42 yr participated in the NPBin and control series. During the series, to reproduce fluids shift observed under microgravity, subjects were supine and head down (-8°). Duration of NPBin was 20 min, rarefaction -20 cm H₂O. Hemodynamic parameters were measured by Finometer. Electrical impedance measurements were used to estimate changes in blood filling of cerebral vessels.RESULTS: Mean values of hemodynamic parameters virtually did not change under NPBin, but NPBin induced oscillations of the parameters synchronous with respiration. Peak-to-peak amplitude under NPBin were: mean arterial pressure, 4 ± 1 (mmHg); stroke volume, 7 ± 3 (mL); and heart rate, 4 ± 1 (bpm). Electrical impedance of the head increased during inspiration. The increase under NPBin was three times greater than under normal breathing.DISCUSSION: Analysis of oscillations gives more information than analysis of mean values. NPBin induces short-term decrease in left ventricle stroke volume and arterial blood pressure during each inspiration; the decrease is compensated by increase after inspiration. NPBin facilitates redistribution of body fluids away from the head.Semenov YS, Melnikov IS, Luzhnov PV, Dyachenko AI. Oscillations of hemodynamic parameters induced by negative pressure breathing in healthy humans. Aerosp Med Hum Perform. 2024; 95(6):297-304.

Роль ацетилхолиновой системы и ее компонентов в формировании постковидных синдромов (обзор)

According to the latest data, COVID-19 is classified as a respiratory virus. However, it has been proven to cause a significant multi-organ dysfunction. Despite the increase in the effectiveness of treatment tactics, a post-COVID-19 symptom complex has been observed in patients after recovery, manifesting itself as cephalalgia, brain fog, high fever, muscle weakness and a decrease (or increase) in arterial pressure. To describe this condition, a clinical characteristic has been proposed: post-acute COVID-19 syndrome (PACS). Approximately 57 % of patients hospitalized with COVID-19 have symptoms of PACS even one year after initial infection with COVID-19. This pathological condition is being actively studied, but the question of the causes of PACS and its development mechanisms remains open. One of the possible reasons behind this symptomatology, in our opinion, is a disorder of the body’s acetylcholine system and its components. The acetylcholine system plays an integral role in various physiological and pathophysiological processes, such as the regulation of the muscular system, immune and inflammatory reactions, wound healing, as well as the development of cardiovascular, respiratory and other diseases. A key way of translating acetylcholine signals in the body is through the use of neurotransmission via a chemical synapse. Based on current literature data, there is reason to believe that viral invasion can significantly change the functional activity of the vagus nerve by disrupting signal transmission in a synapse. We believe that the hyperimmune response caused by COVID-19 triggers a chain of pathological mechanisms that are associated with disrupted nitric oxide production and imbalance in acetylcholine and its receptors. An understanding of these processes may open up prospects for improving the effectiveness of treatment and rehabilitation of patients with COVID-19.

The impact of right ventricular energy failure on the results of pulmonary endarterectomy and balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension

Objective: We aimed to investigate the effect of right ventricular energy failure (RVEF) on hemodynamic and clinical outcomes in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) surgery or balloon pulmonary angioplasty (BPA). Patients and Methods: A total of 100 CTEPH patients planned for PEA or BPA were included in the study. Based on the presence of RVEF during diagnosis, patients divided into two groups. Hemodynamic data from right heart catheterization (RHC) were compared before and after procedures in 3-6 months follow up period. Results: Patients with RVEF revealed a decrease in mean pulmonary artery pressure (mPAP) 54.67±12.27 mmHg to 36.12±11.76 mmHg (p:

Changes in the pulmonary circulation due to gravitational loads in high altitude conditions.

The impact of gravity on the existence of all living things has long been of interest to scientists. The force of the Earth's gravity combined with hypoxia significantly affects blood circulation and blood accumulation in various parts of the human and animal body. To date, the relationship between body position and blood circulation in pulmonary circulation under hypobaric hypoxia has not been sufficiently studied. Therefore, the research aims to determine the possibility of changing the body position in space on the reactions in the pulmonary circulation in the plains and highlands. For this purpose, research was conducted on male Wistar rats, 44 of whom spent 150 days at an altitude of 3200 m above sea level, and 25 representatives of the control group - at an altitude of 164 m. The study revealed that gravitational redistribution of blood in mountainous conditions is less pronounced compared to the control group. This is explained by the remodeling of the vascular wall and an increase in its stiffness. It was found that a change in pulmonary artery pressure at the time of a change in body position was recorded both on the plains and in the highlands. On the plains, when the body position of rats was changed to passive orthostatic, a decrease in systolic and diastolic pulmonary artery pressure was noted, and when the body position was changed to passive anti-orthostatic, an increase in pulmonary artery pressure was observed. The increase in pulmonary artery pressure was a compensatory mechanism due to the increased stiffness of the pulmonary vasculature. The practical significance of this research is to expand the understanding of the pathogenesis of pulmonary hypertension in high-altitude hypoxia.

Light physical activity improves lower limb perfusion asymmetries in older sedentary adults — an exploratory study

Perfusion asymmetries between lower limbs are common even in healthy young individuals, although their physiological significance is unknown. Even in the absence of vascular disease, ageing is among the determinants that seem to accentuate those differences. While it is known that physical activity affects vascular hemodynamics, its specific impact on perfusion asymmetries in healthy elderly individuals is still unclear. This study aimed to identify vascular asymmetries and their variations after a regular program of light exercise in older individuals with age-related comorbidities in the absence of peripheral vascular disease (PVD). Ten participants, mean age 62.4 ± 5.6 years old, were selected following specific criteria. Participants were mostly sedentary, combining one or more common morbidities for this age group — in particular hypertension, overweight and / or diabetes (T2D). Exclusion criteria were an abnormal Ankle-Brachial Index assessed in a standing position at rest and evidence of compromised mobility. All procedures respected the principles of good clinical practice, being previously submitted and approved by the institutional Ethical Commission. Lower limb perfusion was assessed in both feet (anteromedial region) at two time points — day zero (D0) and thirty days later (D30) — using two optical-based technologies — Laser Doppler Flowmetry (LDF) and Polarized Spectroscopy (PSp). These two technologies measure at different depths, with LDF providing deeper tissue readings. During this evaluation period, participants underwent a daily structured program of light exercises based on the FITT principles (F, frequency; I, intensity; T, time and T, type of activity/activity performance) centred in the lower limb perfusion. The group revealed significant asymmetries at D0, where the right foot consistently showed higher values with both technologies correlating positively. At D30, LDF values increased by 57.5% in both feet, meaning that asymmetries disappeared. No significant changes were observed with PSp. Basic cardiovascular functions such as blood pressure and mean arterial pressure were also evaluated, showing significant decreases in systolic pressure and mean arterial pressure. These encouraging results suggest that regular physical activity, even if light in intensity and duration, improves overall hemodynamics and specifically raises perfusion in the lower limbs. These findings should be further explored with the aimof prevention and treatment of PVD. This research was financed by national funds through FCT - Foundation for Science and Technology, I.P. (Portugal), under the [UIDB/04567/2020] and [UIDP/ 04567/2020] programs. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The hybrid (physical-computational) cardiovascular simulator to study valvular diseases

To better understand the impact of valvular heart disease (VHD) on the hemodynamics of the circulatory system, investigations can be carried out using a model of the cardiovascular system. In this study, a previously developed hybrid (hydro-numerical) simulator of the cardiovascular system (HCS) was adapted and used. In our HCS Björk-Shiley mechanical heart valves were used, playing the role of mitral and aortic ones. In order to simulate aortic stenosis (AS) and mitral regurgitation (MR), special mechanical devices have been developed and integrated with the HCS. The simulation results proved that the system works correctly. Namely, in the case of AS − the mean pulmonary arterial pressure was increased due to increased preload of the left ventricle and the decrease in right ventricular preload was caused by a decrease in systemic arterial pressure. The severity of AS was performed based on the transaortic pressure gradient as well as using the Gorlin and Aaslid equations. In the case of severe AS, when the mean gradient was above 40 mmHg, the aortic valve orifice area was 0.5 cm2, which is in line with ACC/AHA guidelines. For the case of MR − with increasing severity of MR, there was a decrease in the left ventricular pressure and an increase in left atrial pressure. Using mechanical heart valves to simulate VHD by the HCS can be a valuable tool for biomedical research, providing a safe and controlled environment to study and understand the pathophysiology of VHD.

Systemic tolerance of intravenous milrinone administration for cerebral vasospasm secondary to non-traumatic subarachnoid hemorrhage

PurposeDelayed cerebral ischemia (DCI) is a severe subarachnoid hemorrhage (SAH) complication, closely related to cerebral vasospasm (CVS). CVS treatment frequently comprises intravenous milrinone, an inotropic and vasodilatory drug. Our objective is to describe milrinone's hemodynamic, respiratory and renal effects when administrated as treatment for CVS. MethodsRetrospective single-center observational study of patients receiving intravenous milrinone for CVS with systemic hemodynamics, oxygenation, renal disorders monitoring. We described these parameters' evolution before and after milrinone initiation (day – 1, baseline, day 1 and day 2), studied treatment cessation causes and assessed neurological outcome at 3–6 months. ResultsNinety-one patients were included. Milrinone initiation led to cardiac output increase (4.5 L/min [3.4–5.2] at baseline vs 6.6 L/min [5.2–7.7] at day 2, p < 0.001), Mean Arterial Pressure decrease (101 mmHg [94–110] at baseline vs 95 mmHg [85–102] at day 2, p = 0.001) norepinephrine treatment requirement increase (32% of patients before milrinone start vs 58% at day 1, p = 0.002) and slight PaO2/FiO2 ratio deterioration (401 [333–406] at baseline vs 348 [307–357] at day 2, p = 0.016). Milrinone was interrupted in 8% of patients. 55% had a favorable outcome. ConclusionIntravenous milrinone for CVS treatment seems associated with significant impact on systemic hemodynamics leading sometimes to treatment discontinuation.

Prospective Observational Study of Volatile Sedation with Sevoflurane After Aneurysmal Subarachnoid Hemorrhage Using the Sedaconda Anesthetic Conserving Device.

Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP). In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of - 5 to - 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed. We included 19 patients with a median age of 61years (range 46-78years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2mm Hg), PBrO2 (31.0 ± 13.2 vs. 32.2 ± 12.4mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support. Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered.

Prevention of hypotension after induction of general anesthesia using point-of-care ultrasound to guide fluid management: a randomized controlled trial.

Hypotension after induction of general anesthesia (GAIH) is common and is associated with postoperative complications including increased mortality. Collapsibility of the inferior vena cava (IVC) has good performance in predicting GAIH; however, there is limited evidence whether a preoperative fluid bolus in patients with a collapsible IVC can prevent this drop in blood pressure. We conducted a single-centre randomized controlled trial with adult patients scheduled to undergo elective noncardiac surgery under general anesthesia (GA). Patients underwent a preoperative point-of-care ultrasound scan (POCUS) to identify those with a collapsible IVC (IVC collapsibility index ≥ 43%). Individuals with a collapsible IVC were randomized to receive a preoperative 500mL fluid bolus or routine care (control group). Surgical and anesthesia teams were blinded to the results of the scan and group allocation. Hypotension after induction of GA was defined as the use of vasopressors/inotropes or a decrease in mean arterial pressure < 65mm Hg or > 25% from baseline within 20min of induction of GA. Forty patients (20 in each group) were included. The rate of hypotension after induction of GA was significantly reduced in those receiving preoperative fluids (9/20, 45% vs 17/20, 85%; relative risk, 0.53; 95% confidence interval, 0.32 to 0.89; P = 0.02). The mean (standard deviation) time to complete POCUS was 4 (2) min, and the duration of fluid bolus administration was 14 (5) min. Neither surgical delays nor adverse events occurred as a result of the study intervention. A preoperative fluid bolus in patients with a collapsible IVC reduced the incidence of GAIH without associated adverse effects. ClinicalTrials.gov (NCT05424510); first submitted 15 June 2022.

Medical Constituents of Ajwain (Trachyspermum ammi) for Human Benefits

Ajwain seed analysis has revealed it to contain fiber (11.9%), carbohydrates (38.6%), tannins, glycosides, moisture (8.9%), protein (15.4%), fat (18.1%), saponins, flavone and mineral matter (7.1%) containing calcium, phosphorous, iron and nicotinic acid. Ajwain fruits yield 2% to 4% brownish essential oil, with thymol as the major constituent (35% to 60%). The non-thymol fraction (thymine) contains para-cymene, γ-terpenine, α- and β-pinenes, diketene, α-terpinene, and carvacrol. Minute amounts of camphene, myrcene, and α-3-carene also have been found in the plant. Alcoholic extracts contain a highly hygroscopic saponin. From the fruits, a yellow, crystalline flavone and a steroid-like substance has been isolated and it also contains 6-O-β-glucopyranosyloxythymol, glucoside and yields 25% oleoresin containing 12% volatile oil (thymol, γ-terpinene, para-cymene, and α- and β-pinene). The principal oil constituents of T. Ammi are carvone (46%), limonene (38%), and dillapiole (9%). Ajwain is administered for curing stomach disorders, a paste of crushed fruits is applied externally for relieving colic pains; and a hot and dry fomentation of the fruits is applied on chest for asthma. Therapeutic uses of T. Ammi fruits include; stomachic, carminative and expectorant, antiseptic and amoebiasis, antimicrobial. Seeds soaked in lemon juice with P runs Amygdalus (badan) are given in curing amenorrhea and it is also used as antipyretic, febrifugal and in the treatment of typhoid fever. The antihypertensive effect of T. Ammi administered intravenously in vivo, and the antispasmodic and bronchodilation actions in vitro showed that calcium channel blockade has been found to mediate the spasmolytic effects of plant materials and it is being considered that this mechanism contributed to their observed result and supported the traditional use of T. Ammi in hyperactive disease states of the gut such as colic and diarrhea as well as in hypertension. Ajwain seeds revealed significant reduction of cough number which may be a result of its potent antitussive effect. The bronchodilator effect of decocted extract of Ajwain on the asthmatic patients’ airways was examined in a subsequent trial study. According to the results, the extract has a relatively bronchodilator effect on asthmatic airways compared to the effect of Theophylline at concentrations used. Ajwain was attributed to have diuretic and antilithiatic activity in ethnopharmacological reports. Accordingly, a human study was performed and in which, seeds of Ajwain were decocted in milk and given orally to volunteers suffering from urinary stone for a nine days period. The results were reported satisfactory against pure ca-oxalate stone. Another activity which has been proved for Ajwain is the antihyperlipidemic property. An in vivo study revealed that Ajwain seeds powder is extensively effective on lipid profile and can decrease total cholesterol, LDL-cholesterol, triglycerides and total lipids. Moreover, organic extract of seeds reduced atherogenic index and increased the level of HDL-cholesterol in albino rabbits. Ajwain was evaluated for the potentiality of antihypertensive and antispasmodic activity. In the related investigation, the aqueous-methanolic extract of the seeds caused a dose dependent decrease in arterial blood pressure in anaesthetized animal models. Furthermore, inhibitory effect on the K+-induced contractions was seen in isolated rabbit aorta and jejunum preparations during the application of Ajwain extract. These findings prove the potential antihypertensive and antispasmodic activity of Ajwain.

Evaluation of propofol and remifentanil combination for controlled hypotension during anesthesia in pediatric nasal endoscopic surgery

Purpose: To investigate the safety and efficacy of propofol in combination with remifentanil for controlled hypotension during pediatric nasal endoscopic surgery. &#x0D; Methods: The study involved 30 patients who underwent controlled hypotension measures with remifentanil during the operation (study group), and 30 patients who did not receive controlled hypotension measures (control group). Various parameters including vital signs, operation time, intraoperative bleeding, surgical field quality, anesthesia quality, postoperative recovery time, adverse reaction rate, pain scores, and serum C-reactive protein levels were compared between the two groups. &#x0D; Results: The results revealed a significant decrease in mean arterial pressure and heart rate in the study group during the operation compared to control group. Moreover, study group exhibited improved operation time, reduced intraoperative bleeding, and better surgical field quality compared to control group. Pain scores and serum C-reactive protein levels were also lower in the study group. However, there were no significant differences in recovery time, anesthesia quality, postoperative adverse reaction rate, or cognitive function between the two groups. &#x0D; Conclusion: Propofol in combination with remifentanil for controlled hypotension is a safe and effective anesthesia approach for pediatric nasal endoscopic surgery. Future studies will require larger sample size from different study centers to improve the robustness of the findings of this study.

Association of Shock Indices with Peri-Intubation Hypotension and Other Outcomes: A Sub-Study of the KEEP PACE Trial.

Based on current evidence, there appears to be an association between peri-intubation hypotension and patient morbidity and mortality. Studies have identified shock indices as possible pre-intubation risk factors for peri-intubation hypotension. Thus, we sought to evaluate the association between shock index (SI), modified shock index (MSI), and diastolic shock index (DSI) and peri-intubation hypotension along with other outcomes. The present study is a sub-study of a randomized controlled trial involving critically ill patients undergoing intubation. We defined peri-intubation hypotension as a decrease in mean arterial pressure <65 mm Hg and/or a reduction of 40% from baseline; or the initiation of, or increase in infusion dosage of, any vasopressor medication (bolus or infusion) during the 30-min period following intubation. SI, MSI, and DSI were analyzed as continuous variables and categorically using pre-established cut-offs. We also explored the effect of age on shock indices. A total of 151 patients were included in the analysis. Mean pre-intubation SI was 1.0 ± 0.3, MSI 1.5 ± 0.5, and DSI 1.9 ± 0.7. Increasing SI, MSI, and DSI were significantly associated with peri-intubation hypotension (OR [95% CI] per 0.1 increase = 1.16 [1.04, 1.30], P = .009 for SI; 1.14 [1.05, 1.24], P = .003 for MSI; and 1.11 [1.04, 1.19], P = .003 for DSI). The area under the ROC curves did not differ across shock indices (0.66 vs 0.67 vs 0.69 for SI, MSI, and DSI respectively; P = .586). Increasing SI, MSI, and DSI were significantly associated with worse sequential organ failure assessment (SOFA) score (spearman rank correlation: r = 0.30, r = 0.40, and r = 0.45 for SI, MSI, and DSI, respectively, all P < .001) but not with other outcomes. There was no significant impact when incorporating age. Increasing SI, MSI, and DSI were all significantly associated with peri-intubation hypotension and worse SOFA scores but not with other outcomes. Shock indices remain a useful bedside tool to assess the potential likelihood of peri-intubation hypotension. ClinicalTrials.gov identifier - NCT02105415.

Lower-Limb Perfusion and Cardiovascular Physiology Are Significantly Improved in Non-Healthy Aged Adults by Regular Home-Based Physical Activities-An Exploratory Study.

Common daily activities including walking might be used to improve cardiovascular health in the presence of disease. Thus, we designed a specific home-based physical activity program to assess cardiovascular indicators in an older, non-active, non-healthy population. Ten participants, with a mean age of 62.4 ± 5.6 years old, were chosen and evaluated twice-upon inclusion (D0), and on day 30 (D30)-following program application. Perfusion was measured in both feet by laser Doppler flowmetry (LDF) and by polarised spectroscopy (PSp). Measurements were taken at baseline (Phase 1) immediately after performing the selected activities (Phase 2) and during recovery (Phase 3). Comparison outcomes between D0 and D30 revealed relevant differences in Phase 1 recordings, namely a significant increase in LDF perfusion (p = 0.005) and a significant decrease in systolic blood pressure (p = 0.008) and mean arterial pressure (MAP) (p = 0.037). A correlation between the increase in perfusion and the weekly activity time was found (p = 0.043). No differences were found in Phase 2, but, in Phase 3, LDF values were still significantly higher in D30 compared with D0. These simple activities, regularly executed with minimal supervision, significantly improved the lower-limb perfusion while reducing participants' systolic pressure and MAP, taken as an important improvement in their cardiovascular status.

Effect of carotid corrected flow time combined with perioperative fluid therapy on preventing hypotension after general anesthesia induction in elderly patients: a prospective cohort study.

Hypotension often occurs following the induction of general anesthesia in elderly patients undergoing surgery and can lead to severe complications. This study assessed the effect of carotid corrected flow time (FTc) combined with perioperative fluid therapy on preventing hypotension after general anesthesia induction in elderly patients. The prospective cohort study was divided into two parts. The first part (Part I) consisted of 112 elderly patients. Carotid FTc was measured using Color Doppler Ultrasound 5min before anesthesia induction. Hypotension was defined as a decrease of greater than 30% in systolic blood pressure (SBP) or a decrease of greater than 20% in mean arterial pressure (MAP) from baseline, or an absolute SBP below 90mmHg and MAP below 60mmHg within 3min after induction of general anesthesia. The predictive value of carotid FTc was determined using receiver operating characteristic (ROC) curve. The second part (Part II) consisted of 65 elderly patients. Based on the results in Part I, elderly patients with carotid FTc below the optimal cut-off value received perioperative fluid therapy at a volume of 8ml/kg of balanced crystalloids (lactated Ringer's solution) in 30min before induction. The effect of carotid FTc combined with perioperative fluid therapy was assessed by comparing observed incidence of hypotension after induction. The area under the ROC for carotid FTc to predict hypotension after induction was 0.876 [95% confidence interval (CI) 0.800-0.952, P <0.001]. The optimal cut-off value was 334.95ms (sensitivity of 87.20%; specificity of 82.20%). The logistic regression analysis revealed that carotid FTc is an independent predictor for post-induction hypotension in elderly patients. The incidence of post-induction hypotension was significantly lower ( P <0.001) in patients with carotid FTc less than 334.95ms who received perioperative fluid therapy (35.71%) compared to those who did not (92.31%). Carotid FTc combined with the perioperative fluid therapy could significantly reduce the incidence of hypotension after the induction of general anesthesia in elderly patients.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event-free survival, and all-cause survival were assessed and analyzed at baseline and posttreatment. Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low-risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6-minutewalking distance(6MWD), pulmonary arterial systolic pressure,pulmonary arterial pressure, right ventricle, andeccentricity index, and significant decreases in N-terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6-month event-free survival and all-cause survival between two groups. Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH.

Anesthetic Aspects of Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Treatment of Pleural Malignancies - Experiences from IORS

Background: Cytoreductive surgery (CRS) with hyperthermic intrathoracic chemotherapy (HITHOC) is a procedure that includes surgical removal of all visible tumor implants and intrathoracic application of gradually heated cytostatic solution. Numerous changes in hemodynamic, respiratory, core body temperature and metabolic parameters are possible during this complex procedure. The aim of this retrospective study was to analyze pathophysiological changes which occur during CRS + HITHOC procedure, and to suggest efficient strategies for perioperative patient care that might reduce complication rate. Methods: The study included 7 patients who underwent CRS + HITHOC in our cancer center. Enhanced Recovery After Surgery (ERAS) guideline for Thoracic Surgery was applied to all patients. Data on intraoperative hemodynamics (mean arterial pressure, stroke volume, heart rate, cardiac output) and temperature variations were collected from medical records and analyzed in three timelines: during the CRS phase, at the beginning, and the end of cytostatic perfusion. Occurrence of respiratory, renal, and cardiac complications was monitored. Results: All patients were respiratory stable during one-lung ventilation, with adequate gas exchange. Hemodynamic stability was compromised at the beginning of cytostatic perfusion, with significant decrease of mean arterial pressure and stroke volume. Two patients required vasopressor support. Average core body temperature was satisfactory in all patients. Coagulation disorders and acute renal failure were not recorded in postoperative period. One patient developed atrial fibrillation which was successfully pharmacologically restored. Conclusion: Our results indicate that goal directed fluid management following ERAS protocol, with maintaining hemodynamic stability and normothermia, could prevent perioperative complications during HITHOC procedure.

Medical Constituents of Ajwain (Trachyspermum ammi) for Human Benefits

Ajwain seed analysis has revealed it to contain fiber (11.9%), carbohydrates (38.6%), tannins, glycosides, moisture (8.9%), protein (15.4%), fat (18.1%), saponins, flavone and mineral matter (7.1%) containing calcium, phosphorous, iron and nicotinic acid. Ajwain fruits yield 2% to 4% brownish essential oil, with thymol as the major constituent (35% to 60%). The non-thymol fraction (thymene) contains para-cymene, γ-terpenine, α- and β-pinenes, dipentene, α-terpinene, and carvacrol. Minute amounts of camphene, myrcene, and α-3-carene also have been found in the plant. Alcoholic extracts contain a highly hygroscopic saponin. From the fruits, an yellow, crystalline flavone and a steroid-like substance has been isolated and it also contains 6-O-β-glucopyranosyloxythymol, glucoside and yields 25% oleoresin containing 12% volatile oil (thymol, γ-terpinene, para-cymene, and α- and β-pinene). The principal oil constituents of T. ammi are carvone (46%), limonene (38%), and dillapiole (9%). Ajwain is administered for curing stomach disorders, a paste of crushed fruits is applied externally for relieving colic pains; and a hot and dry fomentation of the fruits is applied on chest for asthma. Therapeutic uses of T. ammi fruits include; stomachic, carminative and expectorant, antiseptic and amoebiasis, antimicrobial. Seeds soaked in lemon juice with P runus amygdalus (badam) are given in curing amenhorroea and it is also used as antipyretic, febrifugal and in the treatment of typhoid fever. The antihypertensive effect of T. ammi administered intravenously in vivo, and the antispasmodic and bronchodilating actions in vitro showed that calcium channel blockade has been found to mediate the spasmolytic effects of plant materials and it is being considered that this mechanism contributed to their observed result and supported the traditional use of T. ammi in hyperactive disease states of the gut such as colic and diarrhea as well as in hypertension. Ajwain seeds revealed significant reduction of cough number which may be a result of its potent antitussive effect. The bronchodilatory effect of decocted extract of Ajwain on the asthmatic patients’ airways was examined in a subsequent trial study. According to the results, the extract has a relatively bronchodilatory effect on asthmatic airways compared to the effect of Theophylline at concentrations used. Ajwain was attributed to have diuretic and antilithiasis activity in ethnopharmacological reports. Accordingly, a human study was performed and in which, seeds of Ajwain were decocted in milk and given orally to volunteers suffering from urinary stone for a nine days period. The results were reported satisfactory against pure ca-oxalate stone. Another activity which has been proved for Ajwain is the antihyperlipidemic property. An in vivo study revealed that Ajwain seeds powder is extensively effective on lipid profile and can decrease total cholesterol, LDL-cholesterol, triglycerides and total lipids. Moreover, organic extract of seeds reduced atherogenic index and increased the level of HDL-cholesterol in albino rabbits. Ajwain was evaluated for the potentiality of antihypertensive and antispasmodic activity. In the related investigation, the aqueous-methanolic extract of the seeds caused a dose dependent decrease in arterial blood pressure in anaesthetized animal models. Furthermore, inhibitory effect on the K+-induced contractions was seen in isolated rabbit aorta and jejunum preparations during the application of Ajwain extract. These findings prove the potential antihypertensive and antispasmodic activity of Ajwain.

Neurotoxic pesticides change respiratory parameters in early gill-breathing, but not in skin-breathing life-stages of zebrafish (Danio rerio)

Neurotoxic compounds can interfere with active gill ventilation in fish, which might lead to premature death in adult fish, but not in skin-breathing embryos of zebrafish, since these exclusively rely on passive diffusion across the skin. Regarding lethality, this respiratory failure syndrome (RFS) has been discussed as one of the main reasons for the higher sensitivity of adult fish in the acute fish toxicity test (AFT), if compared to embryos in the fish embryo toxicity test (FET). To further elucidate the relationship between the onset of gill respiration and death by a neurotoxic mode of action, a comparative study into oxygen consumption (MO2), breathing frequency (fv) and amplitude (fampl) was performed with 4 d old skin-breathing and 12 d old early gill-breathing zebrafish. Neurotoxic model substances with an LC50 FET/AFT ratio of > 10 were used: chlorpyrifos, permethrin, aldicarb, ziram, and fluoxetine. Exposure to hypoxia served as a positive control, whereas aniline was tested as an example of a narcotic substance interfering non-specifically with gill membranes. In 12 d old larvae, all substances caused an increase in MO2, fv and partly fampl, whereas effects were minor in 4 d old embryos. An increase of fv in 4 d old embryos following exposure to chlorpyrifos, aldicarb and hypoxia could not be correlated with an increased MO2 and might be attributed either to (1) to the successfully postponed decrease of arterial partial pressure of oxygen (PO2) through support of skin respiration by increased fv, (2) to an unspecific stimulation of the sphincter muscles at the base of the gill filaments, or (3) to the establishment of oxygen sensing for later stages. In gill-breathing 12 d old zebrafish, a concentration-dependent increase of fv was detected for aniline and chlorpyrifos, whereas for aldicarb, fluoxetine and permethrin, a decline of fv at higher substance concentrations was measured, most likely due to the onset of paralysis and/or fatigue of the gill filament sphincter muscles. Since alterations of fv serve to postpone the decrease in arterial PO2 and MO2 increased with decreasing fv, the respiratory failure syndrome could clearly be demonstrated in 12 d old zebrafish larvae. Passive respiration across the skin in zebrafish embryos could thus be confirmed as a probable reason for the lower sensitivity of early life-stages to neurotoxicants. Integration of respiratory markers into existing testing protocols with non-protected developmental stages such as embryos might help to not underestimate the toxicity of early life-stages of fish.

Lidocaine, Esmolol, and Beyond: A Comprehensive Analysis of Hemodynamic Stress during Laryngoscopy and Intubation

Aim: To evaluate the haemodynamic stress response in combination of lidocaine and esmolol versus lidocaine or esmolol alone during laryngoscopy and intubation Methods: This research comprised 60 patients who provided written permission and met the inclusion and exclusion criteria. Selected patients were randomly assigned to one of three groups based on a computer-generated random number: lignocaine 1.5 mg/kg (n=40), esmolol 2mg/kg (n=40), or lignocaine 1mg/kg and esmolol 1mg/kg (n=40). This research comprised patients aged 20 to 42 who had elective procedures under general anaesthetic and had ASA I and II. Patients with contraindications to beta blockers, such as bronchial asthma, COPD, a basal heart rate of 60 beats per minute, respiratory impairment, and documented reactions to local anaesthetics. Results: There were no significant variations in age, preoperative heart rate, or blood pressure between the groups. Males and females were approximately equally dispersed throughout all groupings. Following the delivery of the test medicines, all three groups saw a substantial drop in heart rate (Group E 61.23±3.64, Group L 73.25±5.36, Group LE 72.23±5.36) (p&lt;0.001). Four Group E patients developed bradycardia. (HR &lt;60). Although both Group LE and Group L showed near baseline values, Group L showed near baseline values until the third minute, whereas Group LE showed a continuous reduction in heart rate rates. After 30 minutes, all three groups' heart rates were statistically insignificant. Following induction and administration of the test medicines, systolic, diastolic, and hence mean arterial blood pressure lowers gradually in all three groups (p&lt;0.001). (This is for systolic blood pressure.). Group E 97.36±5.69, Group L 125.39±6.36, Group LE 116.78±4.78) Group E 60.034.69, Group L 82.935.36, Group LE 72.034.78) (Group E 72.10±3.69, Group L 96.90±3.85, Group LE 86.44±2.87) Before intubation, patients in Group E experienced substantial decreases in systolic, diastolic, and mean arterial blood pressure (less than 20% of baseline). Following intubation, blood pressure levels in Group LE were near baseline until the 30th minute (p&lt;0.001). Group E had a consistent fall in all three blood pressure readings following intubation until the fifth minute. Group E's blood pressures were likewise around baseline at the 15th and 30th minutes. Until the 15th minute, Group L had a considerable rise in all three blood pressures. Conclusion: As a result, esmolol and lidocaine together are a safe and effective strategy to minimise laryngoscopy responses to intubation and extubation, lowering myocardial oxygen consumption and the risk of myocardial ischemia under general anaesthesia.

Characteristics of clinical course and comorbidity formation of arterial hypotension in farmer population

The criteria for a significant decrease in arterial pressure is considered to be an element of arterial pressure variability or a certain degree of manifestation. Implementation of various forms of epidemiologic research in order to establish the basis for new approaches to early diagnosis of arterial hypotension, to improve the prognosis, and to achieve high efficiency in prevention has become a necessity and a necessity for farmers in the conditions of Uzbekistan. In the regions of Uzbekistan, there is a great need and necessity to solve the problems of arterial hypotension in this approach. The lack of scientific study of this issue, especially among the large population of Uzbekistan engaged in farming, undoubtedly requires science to fill the “gap” in this direction. Keywords: arterial hypotension, cardiovascular diseases (CVD), chronic heart failure, cardiocomorbidity, non-infectious diseases (NID), arterial pressure variability, independent control of arterial pressure (ABMNQ).