Reduction In Blood Volume Research Articles

Role of plant bioactive as diuretics: General considerations and mechanism of diuresis.

Medicinal plants have been found beneficial in the control and therapy of many ailments as they contain bioactive compounds, and many of them are used as precursors in the biosynthesis of natural medicines. Diuretics are used as a primary treatment in patients with edema associated with liver cirrhosis and kidney diseases, hyperkalemia, hypertension, heart failure, or renal failure. Furthermore, they are also used to increase the excretion of sodium and reduce blood volume. Due to various adverse events associated with synthetic diuretics, there is a need to investigate alternate plant-based bioactive components that have effective diuretic activity with minimal side effects. This review compiled the reported bioactive compounds from different plant sources along with their mechanisms of diuretic activity. Different sources were used to collect information regarding herbal plants with therapeutic value as diuretics. These included published peer-reviewed journal articles, scholarly articles from StatPearls, and search engines like Google Scholar, PubMed, Scopus, Springer, ScienceDirect, Wiley, etc. Results: In this review, it was found that flavonoids like rutin, acacetin, naringenin, etc. showed significant diuretic activity in experimental models by various mechanisms, but mostly by blocking the sodium-potassium-chloride co-transporter, while some bioactive compounds showed diuretic actions via other mechanisms as well. Research on clinical trials of these isolated bioactive compounds needs to be further conducted. Thus, this review provides an understanding of the potential diuretic bioactive compounds of plants for further research and pharmaceutical applications.

Phenotyping lung function disorders in respiratory Long-COVID

Dyspnea is frequently complained for several weeks in Long-COVID, still being its underlying pathophysiology poorly investigated in the clinical setting. Aim: to investigate the lung functional pattern of Long-COVID patients and healthy controls (HC). Non-smokers aged ≥18years, discharged after COVID pneumonia were investigated, were classified as low dyspnea scorers (LDS) or high dyspnea scorers (HDS) if they were not complaining or otherwise still complaining dyspnea 12-16 weeks after discharge. A group of non-smoking HC was compared. Spirometric parameters; usual DLCO; simultaneous single-breath DLNO (sDLNO) and DLCO (sDLCO); lung capillary blood volume (Vc), and expiratory nitric oxide (eNO) were assessed. Their linear association was explored by correlation analysis. Area under the curve (AUC) were used to determine the best predictors of being HC, LDS or HDS, and to establish optimal cut-off values. 40 Long-COVID patients (19 LDS; 21 HDS) and 28 HC were investigated. FEV1, VC and FEV1/VC were equal in LSD and HSD. A decreasing trend (p<0.0001) for DLCO, sDLCO, sDLNO and Vc, and a corresponding increasing trend (p<0.0001) for sDLNO/sDLCO and eNO were detected from HC to HDS patients. sDLNO/sDLCO and Vc resulted the best predictors of belonging to the HDS group. Optimal cut-off values were 113.5 for sDLNO/sDLCO ratio and 58.5 for Vc, respectively. Data suggest the reduction of lung capillary blood volume as the main disorder in these cases and contribute to phenotyping respiratory troubles in Long-COVID. These disorders would be otherwise neglected by usual lung function parameters, due their low specificity.

Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status.

Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock. We measured HR, SBP, and CRM in 172 human subjects (19-55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater ( p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94-0.97) compared with 0.91 (0.89-0.94) for SI ( p = 0.0002). Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia. Diagnostic Test or Criteria; Level III.

Effects of dapagliflozin on cardiac function indexes and serum MCP-1 levels in patients with Type 2 diabetes mellitus complicated with heart failure

ABSTRACT Type 2 diabetes mellitus (T2DM) and heart failure (HF) are common in clinic, and they often coexist, triggering poor prognosis of patients and increasing hospitalization rates and mortality. Due to some common pathophysiological mechanisms between T2DM and HF, the two have synergistic effects and require collaborative management . In terms of the treatment of T2DM combined with HF, the effects of drugs on both diseases need to be considered to prevent the impact of HF drugs on glycometabolism. As an SGLT2 inhibitor, dapagliflozin can excrete glucose through the kidneys, reduce blood volume, decrease cardiac load to some extent, improve HF symptoms, and better control blood glucose . Therefore, this study selected 60 HF patients complicated with T2DM as the research subjects, and divided them into control group (CLG, conventional medical treatment) and observation group (ONG, dapagliflozin treatment) to explore the effects of dapagliflozin through comparative analysis. According to the results, compared with CLG, ONG had better improvement of blood glucose, cardiac function, and serum levels (P < 0.05), and a lower rehospitalization rate (P < 0.05), with no obvious between-group differences in the incidence of hypotension and emaciation (P > 0.05). These results showed that dapagliflozin in the treatment of T2DM with HF can improve blood glucose levels, cardiac function indexes and inflammatory factor levels, and decrease rehospitalization rates, presenting good clinical efficacy.

Factors affecting intradialytic hepatic oxygenation: Associations between ultrafiltration rate and changes in systemic blood pressure

Hepato-splanchnic circulation influences the oxygenation of abdominal organs and is important in preventing a reduction in intradialytic blood volume. However, the association between changes in intradialytic hepato-splanchnic circulation and clinical factors remain unknown. We enrolled 91 hemodialysis (HD) patients (20 with intradialytic hypotension (IDH) and 71 without IDH). During HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting hepato-splanchnic circulation and oxygenation, was monitored. Changes in hepatic rSO2 at the lowest systolic blood pressure (BP) during HD were analyzed to identify associations with clinical factors. Hepatic rSO2 levels were 55.8 ± 15.3% before HD and 53.8 ± 14.9% at the lowest systolic BP; therefore, % changes in hepatic rSO2 were -2.7 ± 11.3%. These values were significantly lower in patients with IDH than in those without IDH (-13.8 ± 9.3% vs 0.4 ± 9.8%, p < 0.001). Multivariable regression analysis showed that % changes in hepatic rSO2 were independently associated with % changes in systolic BP (standardized coefficient: 0.416) and ultrafiltration rate (-0.206). Furthermore, % changes in mean BP (0.304) were identified as affecting % changes in hepatic rSO2 instead of those in systolic BP. Changes in intradialytic hepatic oxygenation is associated with ultrafiltration rate and changes in systemic BP. Further studies are required to clarify the directionality of the association between changes in hepatic oxygenation and changes in systemic BP during HD.

Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms.

Natriuretic peptides (NPs) are the principal expression products of the endocrine function of the heart. They exert several beneficial effects, mostly mediated through guanylate cyclase-A coupled receptors, including natriuresis, diuresis, vasorelaxation, blood volume and blood pressure reduction, and regulation of electrolyte homeostasis. As a result of their biological functions, NPs counterbalance neurohormonal dysregulation in heart failure and other cardiovascular diseases. NPs have been also validated as diagnostic and prognostic biomarkers in cardiovascular diseases such as atrial fibrillation, coronary artery disease, and valvular heart disease, as well as in the presence of left ventricular hypertrophy and severe cardiac remodeling. Serial measurements of their levels may be used to contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations and to guide tailored pharmacological and non-pharmacological strategies with the aim to improve clinical outcomes. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new targeted cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors to the current management of heart failure, novel promising molecules including M-atrial natriuretic peptide (a novel atrial NP-based compound) have been tested for the treatment of human hypertension with promising results. Moreover, different therapeutic strategies based on the molecular mechanisms involved in NP regulation and function are under development for the management of heart failure, hypertension, and other cardiovascular conditions.

Blood Collection Guidelines and Techniques in Small Laboratory Animals for Biomedical Research: A Systematic Review

Venipuncture, phlebotomy, or blood collection is a specific and important procedure for collecting samples from research animals. Many research techniques require multiple blood samples to analyze the data. In truth, laboratory rodents are smaller in size and have a relatively low blood volume compared to humans. Any major reduction in blood volume would have an extreme consequence on the animal’s biology. Consequently, the safe amount of blood samples that can be obtained from an animal and the frequency of safe blood collection are the two extremely important factors to consider for protecting the health and welfare of the animals. Because stress to the study animal affects the research outcome, the techniques used should allow blood sampling while diminishing the potential for pain, suffering, avoidable stress, or unexpected results in the study animal. Several regulatory bodies have issued guidelines for collecting blood from study animals. Information on general blood collection guidelines and the different blood collection sites in laboratory animal species are scattered across various literature. This review presents a consolidated data on all the guidelines and precautions involved in blood sampling from small laboratory animals. Using suitable keywords, reference documents were collected from online databases like PubMed, Embase, Scopus, Medline and Google Search. However, researchers are the better judges in choosing the right blood collection method to use in their study, keeping in mind the welfare and health of their research animals.

Individually adjusted absolute blood volume feedback control: A promising solution for intradialytic hypotension.

Intradialytic hypotension (IDH) remains one of the most frequent complications associated to hemodialysis (HD), frequently triggered by a reduction in absolute blood volume (ABV) not compensated by vascular refilling. A recently developed dilutional method allows routinary measurement of ABV and, by a simple algorithm, may turn blood volume monitor (BVM) guided UF (ultrafiltration) biofeedback into an ABV control, automatically adjusting UF rate to maintain ABV above a preset threshold. The aim of this study is to identify an individual critical ABV threshold and test the ability of an ABV feedback control to avoid IDH. We studied 24 patients throughout three consecutive midweek HD treatments. ABV and blood pressure (BP) were measured every 30 min and anytime the patient referred any symptoms to identify each patient's critical ABV (ABV at the time of hypotension). A fixed bolus dilution approach at the start of HD was used to calculate ABV. Then, patients were followed through three additional HD treatments and IDH development was analyzed. Seventy-one treatments performed in 24 patients. ABV monitoring showed a constant decrease as HD treatment progressed. Thirteen IDH events were observed in eight different patients, with a mean systolic BP drop in IDH treatments of 37.38 ± 4.31 mmHg and a mean adjusted ABV at hypotension of 71.07 ± 14.88mL/kg. Critical ABV was individually set in patients prone to IDH. As expected, ABV feedback control successfully maintained ABV over preset critical ABV. IDH events were avoided in 21 out of 22 treatments performed. ABV drop was successfully reduced, as well as SBP drop (despite similar UF than prior to ABV feedback control implementation). ABV feedback control avoided IDH in 21 out of 22 treatments performed by maintaining blood volume above critical ABV, significantly reducing ABV variations without compromising prescribed UF.

Hyponatremia Associated with Congestive Heart Failure: Involvement of Vasopressin and Efficacy of Vasopressin Receptor Antagonists

Hyponatremia is frequently found in patients with congestive heart failure. A reduction in effective circulatory blood volume in a volume-expanded patient with decreased cardiac output is linked to a baroreceptor-mediated non-osmotic release of arginine vasopressin (AVP). The increased production of AVP and salt and water retention in the proximal and distal tubules of the kidney by humoral, hemodynamic, and neural mechanisms increase circulatory blood volume and contribute to hyponatremia. Recent studies have indicated that hyponatremia predicts the short-term and long-term prognosis of heart failure by increasing cardiac death and rehospitalization. In addition, the early development of hyponatremia in acute myocardial infarction also predicts the long-term prognosis of worsening heart failure. AVP V2 receptor antagonism may relieve water retention, but it is unknown whether the V2 receptor inhibitor, tolvaptan, improves the long-term prognosis of congestive heart failure. The newly identified natriuretic factor in renal salt wasting has the potential of improving clinical outcomes when combined with a distal diuretic.

Reader Response: Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow).

Ng et al.1 recently reported a 25% prevalence of hypoperfusion—a >15% reduction of cerebral blood flow (CBF) or cerebral blood volume (CBV) from the mirror region on CT perfusion imaging—within the 24-hour infarct window, despite complete anterior circulation recanalization (TICI 2c/3), which negatively affected functional outcome. These findings contrast with our earlier finding of 6% (2/33) hypoperfused infarcts, where the 24-hour arterial spin labeling (ASL)-CBF images were analyzed according to the Alberta Stroke Program Early CT Score (ASPECTS) template.2 We have reanalyzed our data set considering the entire middle cerebral arterial (MCA) territory, irrespective of ASPECTS. After excluding areas with confluent hemorrhagic transformation or parenchymal hematoma on the 24-hour MRI, consensus by 2 raters (kappa = 0.752) identified only 2 additional patients exhibiting patchy mild-to-moderate hypoperfusion with volumes too small to be reliably measured on ASL images, for a total prevalence of 4 of 33 patients (12%). After excluding patients with missing mRS (n = 2) or associated infarcts outside the MCA territory (n = 5), univariate analysis showed no significant association of “no-reflow” presence with a 3-month mRS of 0–1 or 0–2. A multivariate analysis was precluded by low occurrence of no-reflow. Taken together with this article and another recent report,3 the prevalence of no-reflow after recanalized MCA stroke appears to stand ∼15–20%, depending on the perfusion modality used, and often involves small areas. The true impact on clinical outcome remains unclear.3

Impact of rigid cervical collars on the vital signs and cervical vasculature: Should we be on the alert for anything?

ObjectiveIn this study, it was aimed to reveal the effect of RCC application on vital signs and physiology of the neck vascular structures. MethodsThe study was designed as a prospective interventional study on 11 volunteers. The factors that would affect the hemodynamics of the volunteers were standardized before the measurements. The vital signs before and after RCC were measured and under the guidance of ultrasonography (USG), internal jugular vein cross-sectional area (CSA), diameter of the common carotid artery (CCAD), peak systolic velocity (PSV). end-diastolic velocity (EDV), time-averaged maximum velocity (TAMAX), Pulsatility Index, Resistivity Index, time averaged mean velocity (TAMEAN), Volume Flow (FV) measurements were made and compared with each other. ResultsAmong 11 volunteers, the study included 5 women (45.5%). 10 min of RCC application was associated with a reduction of the heart rate by 7.9 bpm (95% CI 4.84–10.98) (pre-collar 74.73 + −8.84, post-collar 66.82 + −9.05, p < 0.001). A corresponding 7.18 mmHg (95% CI 2.11–12.25) decrease in systolic blood pressure (pre-collar mean 115.82 mmHg + −12.55, post-collar mean 108.64 mmHg + −11.46, p = 0.01) and 108.55 mL/min reduction of mean common carotid artery blood volume (95% CI 22.28–194.82) (pre-collar 590.14 mL/min + −194.63, post-collar 481.59 mL/min + −279.36, p = 0.019) were noted. Internal jugular vein CSA has decreased for 0.17 cm2 (95% CI 0.05–0.29) (pre-collar CSA 0.53 + −0.29, post-collar CSA 0.36 + −0.17, p = 0.012). ConclusionIn healthy volunteers, RCC application lasting for ten minutes may reduce systolic blood pressure and heart rate, while decreasing blood volume in both the common carotid artery and the internal jugular vein. It has also been noted that the collapse is larger in the internal jugular vein than in the common carotid artery following the pressure applied by RCC.

Hypercalcaemia secondary to hypophysitis and cortisol deficiency: another immunotherapy-related adverse event.

Hypercalcaemia is a common complication seen in malignancy, frequently due to paraneoplastic parathyroid hormone-related peptide production or osteolytic bony metastases. We present a 58-year-old female with immunotherapy-mediated hypophysitis causing secondary cortisol deficiency resulting in severe glucocorticoid-responsive hypercalcaemia. Whilst hypophysitis is a well recognised adverse event in those receiving immunotherapy for advanced malignancy, it does not typically present with hypercalcaemia. The mechanism responsible for hypercalcaemia due to hypocortisolaemia has not been fully elucidated although hypotheses include the effects of volume depletion and thyroxine's action on bone. Prompt treatment with glucocorticoids caused an improvement in the patient's symptoms and corrected her hypercalcaemia which later returned after an attempted glucocorticoid wean. With the increasing uptake of immunotherapy, clinicians should be aware of this unusual presentation of immunotherapy-related hypophysitis and secondary hypocortisolaemia which can be life-threatening if the diagnosis is delayed. Immunotherapy can cause inflammation of the pituitary gland resulting in secondary hypocortisolaemia, which can, though rarely, present as hypercalcaemia. Secondary hypocortisolaemia requires prompt recognition and treatment with glucocorticoids. Glucocorticoid replacement leads to rapid clinical and biochemical improvement in these patients. The differential diagnosis for glucocorticoid-responsive hypercalcaemia extends beyond granulomatous disorders (e.g. sarcoidosis, tuberculosis) to adrenocorticotrophic hormone and cortisol deficiency, particularly in patients receiving immunotherapy. Hypocortisolaemia can lead to hypercalcaemia through various proposed mechanisms. Low serum glucocorticoids are associated with reduced blood volume, thus reducing renal calcium excretion. In addition, without glucocorticoid's inhibitory action, thyroxine appears to drive calcium mobilisation from bone.

How does alzheimer’s disease, atherosclerosis and comorbid alzheimer’s disease and atherosclerosis impact neurovascular function?

AbstractBackgroundThe brain is an energy hungry organ, consuming approximately 20% of the body’s energy supply (Clark &amp; Sokoloff 1999). Due to its high energy demands the brain has developed a critical mechanism termed neurovascular coupling (NVC). NVC is the relationship between neuronal activity and a subsequent increase in blood flow to the same brain region. This mechanism is suggested to be impaired in many disorders, including Alzheimer’s disease (AD) (Kisler et al., 2017). Additionally, approximately 90% of individuals living with dementia have a comorbidity (Browne et al., 2017), with some of the most common comorbidities being cardiovascular disease (Tini et al., 2020) and type 2 diabetes (Santiago et al., 2021). Therefore, we wanted to investigate neurovascular function in AD and comorbid mixed models of AD and atherosclerosis.MethodFour separate groups of mice were used, aged 9‐12 months: AD (APP/PS1 (B6;C3 Tg(APPswe,PSEN1dE9)85Dbo/Mmjax)), WT (APP/PS1‐WT littermates) , atherosclerosis (WT + rAAV8‐mPCSK9‐D377Y + Western Diet) and Mixed AD and atherosclerosis (APP/PS1 + rAAV8‐mPCSK9‐D377Y + Western Diet). At 9m mice completed the novel object recognition test (NOR) to assess cognition. Following this, a thinned window surgery was completed. One‐week post‐surgery 2‐dimensional optical imaging spectroscopy (2D‐OIS) was utilised to investigate changes in cerebral haemodynamics, in response to a whisker stimulation in awake mice. A separate imaging session in anaesthetised mice was also completed, using 2D‐OIS concurrent with electrophysiology to assess neurovascular coupling. Immunohistochemistry was performed to assess amyloid plaque load within the brain.ResultIn the awake imaging session we found that neurovascular function was preserved in the AD group. However, mice in the atherosclerosis group showed a reduction in blood volume in response to a 2s‐whisker stimulation, compared to the WT group. We hypothesised that the mixed model would have the greatest impairment in the neurovascular response, however this was not observed and this group showed an evoked‐blood volume change in between levels of AD and atherosclerosis only groups.ConclusionPreliminary results suggest that neurovascular function is impaired in mouse models of atherosclerosis but not in the AD or mixed models. Analysis is ongoing to determine how neural activity and AD pathology are impacted by comorbidity.

Hemoglobin Determination Using Pulse Co-Oximetry and Reduced-Volume Blood Gas Analysis in the Critically Ill: A Prospective Cohort Study.

Hospital-acquired anemia is common in patients hospitalized in the intensive care unit (ICU). A major source of iatrogenic blood loss in the ICU is the withdrawal of blood for laboratory testing. The aim of our study was to analyze the feasibility and accuracy of non-invasive spot-check pulse co-oximetry (SpHb), and a reduced-volume blood gas analysis (ABG Hb) for the determination of Hb concentration in critically ill patients. Comparisons between Hb determined with test devices and the gold standard-complete blood count (CBC)-were performed using Bland-Altman analysis and concordance correlation coefficient (CCC). The limits of agreement between SpHb and CBC Hb were -2.0 [95%CI -2.3-(-1.7)] to 3.6 (95%CI 3.3-3.9) g/dL. The limits of agreement between ABG Hb and CBC Hb were -0.6 [95%CI -0.7-(-0.4)] to 2.0 (95%CI 1.9-2.2) g/dL. Spearman's coefficient and CCC between ABG Hb and CBC Hb were 0.96 (95%CI 0.95-0.97, p &lt; 0.001) and 0.91 (95%CI 0.88-0.92), respectively. Non-invasive spot-check Hb co-oximetry is not sufficiently accurate for the monitoring of hemoglobin concentration in critically ill patients. Reduced volume arterial blood gas analysis has acceptable accuracy and could replace complete blood count for the monitoring of Hb concentration in critically ill patients, leading to a significant reduction in blood volume lost for anemia diagnostics.

Left ventricular T1-mapping in diastole versus systole in patients with mitral regurgitation

Cardiovascular magnetic resonance T1-mapping enables myocardial tissue characterisation, and is capable of quantifying both intracellular and extracellular volume. T1-mapping is conventionally performed in diastole, however, we hypothesised that systolic readout would reduce variability due to a reduction in myocardial blood volume. This study investigated whether T1-mapping in systole alters T1 values compared to diastole and whether reproducibility alters in atrial fibrillation compared to sinus rhythm. We prospectively identified 103 consecutive patients recruited to the Mitral FINDER study who had T1 mapping in systole and diastole. These patients had moderate or severe mitral regurgitation and a high incidence of ventricular dilatation and atrial fibrillation. T1, ECV and goodness-of-fit (R2) values of the T1 times were calculated offline using Circle cvi42 and in house-developed software. Systolic T1 mapping was associated with fewer myocardial segments being affected by artefact compared to diastolic T1 mapping [217/2472 (9%) vs 515/2472 (21%)]. Mean native T1 values were not significantly different when measured in systole and diastole (985 ± 26 ms vs 988 ± 29 respectively; p = 0.061) and mean post-contrast values showed similar good agreement (462 ± 32 ms vs 459 ± 33 respectively, p = 0.052). No clinically significant differences in ECV, native T1 and post-contrast T1 were identified between diastolic and systolic T1 maps in males versus females, or in patients with permanent atrial fibrillation versus sinus rhythm. A statistically significant improvement in R2 value was observed with systolic over diastolic T1 mapping in all analysed maps (n = 411) (96.2 ± 1.4% vs 96.0 ± 1.4%; p < 0.001) and in subgroup analyses [Sinus rhythm: 96.1 ± 1.4 vs 96.3 ± 1.4 (n = 327); p < 0.001. AF: 95.5 ± 1.3 vs 95.9 ± 1.2 (n = 80); p < 0.001] [Males: 95.8 ± 1.4 vs 96.1 ± 1.3 (n = 264); p < 0.001; Females: 96.2 ± 1.3 vs 96.4 ± 1.4 (n = 143); p = 0.009]. In conclusion, myocardial T1 mapping is associated with similar T1 and ECV values in systole and diastole. Furthermore, systolic acquisition is less prone to gating artefact in arrhythmia.

Abstract 11115: Impella Preserves Systemic, Coronary, and Cerebral Blood Flows During Ventricular Fibrillation by Establishing the Acute Fontan Circulation

Introduction: The ventricular fibrillation (VF) often occurs in acute heart failure patients with Impella support, percutaneous transvalvular left ventricular assist device. Although Impella can preserve blood pressure in some VF patients, the hemodynamic mechanism of Impella during VF remains unclear. Aim: In this study, we examined the impact of Impella on hemodynamics and cerebral and coronary blood flows in a goat model of VF. We also addressed the optimal blood volume status to maintain the Impella circulation during VF. Methods: In six goats, we inserted Impella CP via the left carotid artery. We simultaneously recorded right (RAP) and left atrial pressure (LAP), central blood pressure at ascending aorta (CBP), and the blood flows of pulmonary artery (PA), left coronary circumflex artery (LCX), and right carotid artery (CA). The VF was induced by direct current. We compared the impact of Impella support level (P0, P4 and P8) on hemodynamics and each blood flow. Under P8-Impella supported VF condition, we withdrew blood continuously and observed the left ventricular (LV) suction point at which a frequent negative LV pressure occurred. Results: As shown in Fig. 1 and 2, Impella maintained hemodynamics flow-dependently, indicating the establishment of acute Fontan circulation. In P8-Impella support, systemic (PA flow), LCX and CA blood flows were preserved by 50.1±27.7, 50.7±12.5 and 67.3±5.6%. from baseline, respectively. The blood volume reduction induced the suction of Impella (Fig. 3) at RAP below 9.9±1.9 mmHg. Conclusions: Impella establishes the acute Fontan circulation and preserves hemodynamics including coronary and cerebral blood flows during VF. The optimal blood volume status should be considered to maintain the Impella operation during VF.

Small molecule angiotensin converting enzyme inhibitors: A medicinal chemistry perspective.

Angiotensin-converting enzyme (ACE), a zinc metalloprotein, is a central component of the renin-angiotensin system (RAS). It degrades bradykinin and other vasoactive peptides. Angiotensin-converting-enzyme inhibitors (ACE inhibitors, ACEIs) decrease the formation of angiotensin II and increase the level of bradykinin, thus relaxing blood vessels as well as reducing blood volume, lowering blood pressure and reducing oxygen consumption by the heart, which can be used to prevent and treat cardiovascular diseases and kidney diseases. Nevertheless, ACEIs are associated with a range of adverse effects such as renal insufficiency, which limits their use. In recent years, researchers have attempted to reduce the adverse effects of ACEIs by improving the selectivity of ACEIs for structural domains based on conformational relationships, and have developed a series of novel ACEIs. In this review, we have summarized the research advances of ACE inhibitors, focusing on the development sources, design strategies and analysis of structure-activity relationships and the biological activities of ACE inhibitors.

Long-lasting dyspnoea in patients otherwise clinically and radiologically recovered from COVID pneumonia: a probe for checking persisting disorders in capillary lung volume as a cause.

BackgroundDuring SARS-CoV-2 infection, diffuse alveolar damage and pulmonary microvascular abnormalities are critical events that result in gas exchange disorders of varying severity and duration. The only measure of carbon monoxide (CO) diffusing capacity (DLCO) is unable to distinguish the alveolar from the vascular side of present and residual diffusive abnormalities, and measure of nitric oxide (NO) diffusing capacity (DLNO) is also recommended. Dyspnoea, despite being understudied, persists in a significant proportion of patients for several weeks after hospital discharge. The goal of this study was to look into the underlying cause of long-term dyspnoea in patients who were "clinically and radiologically recovered" from COVID pneumonia by assessing DLCO and DLNO at the same time.MethodsPatients of both genders, aged ≥18 years, who had a CT scan showing complete resolution of COVID-related parenchymal lesions were recruited consecutively. Spirometrical volumes, blood haemoglobin, SpO2, DLCO, DLNO and capillary blood volume (Vc) were measured. Data from patients without dyspnoea (group A) and from patients still claiming dyspnoea after 12-16 weeks from their hospital discharge (group B) were statistically compared.ResultsForty patients were recruited: 19 in group A and 21 in group B. Groups were comparable for their general characteristics and spirometrical volumes, that were in the normal range. Mean values for DLCO, DLNO and Vc were significantly and substantially lower than predicted only in patients of group B (p<0.011; p<0.0036; p<0.02; p<0.001, respectively). The DLNO/ DLCO ratio was higher in group B (p<0.001) and inversely correlated to Vc values (-0.3636).ConclusionsThe single-breath, simultaneous measurement of DLCO, DLNO, and Vc demonstrated that problems with blood gas exchange can persist even after parenchymal lesions have healed completely. Regardless of the normality of spirometric volumes, there was a significant reduction in lung capillary blood volume. In these patients, the cause of long-term dyspnoea may be related to hidden abnormalities in the vascular side of diffusive function. In the near future, novel therapeutic approaches against residual and symptomatic signs of long-COVID are possible.

A change of heart: Mechanisms of cardiac adaptation to acute and chronic hypoxia.

Over the last 100 years, high‐altitude researchers have amassed a comprehensive understanding of the global cardiac responses to acute, prolonged and lifelong hypoxia. When lowlanders are exposed to hypoxia, the drop in arterial oxygen content demands an increase in cardiac output, which is facilitated by an elevated heart rate at the same time as ventricular volumes are maintained. As exposure is prolonged, haemoconcentration restores arterial oxygen content, whereas left ventricular filling and stroke volume are lowered as a result of a combination of reduced blood volume and hypoxic pulmonary vasoconstriction. Populations native to high‐altitude, such as the Sherpa in Asia, exhibit unique lifelong or generational adaptations to hypoxia. For example, they have smaller left ventricular volumes compared to lowlanders despite having larger total blood volume. More recent investigations have begun to explore the mechanisms underlying such adaptive responses by combining novel imaging techniques with interventions that manipulate cardiac preload, afterload, and/or contractility. This work has revealed the contributions and interactions of (i) plasma volume constriction; (ii) sympathoexcitation; and (iii) hypoxic pulmonary vasoconstriction with respect to altering cardiac loading, or otherwise preserving or enhancing biventricular systolic and diastolic function even amongst high altitude natives with excessive erythrocytosis. Despite these advances, various areas of investigation remain understudied, including potential sex‐related differences in response to high altitude. Collectively, the available evidence supports the conclusion that the human heart successfully adapts to hypoxia over the short‐ and long‐term, without signs of myocardial dysfunction in healthy humans, except in very rare cases of maladaptation.

Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.

Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.