Increase In Cardiac Output Research Articles

Repository Describing the Anatomical, Physiological, and Biological Changes in an Obese Population to Inform Physiologically Based Pharmacokinetic Models.

BackgroundObesity is associated with physiological changes that can affect drug pharmacokinetics. Obese individuals are underrepresented in clinical trials, leading to a lack of evidence-based dosing recommendations for many drugs. Physiologically based pharmacokinetic (PBPK) modelling can overcome this limitation but necessitates a detailed description of the population characteristics under investigation.ObjectiveThe purpose of this study was to develop and verify a repository of the current anatomical, physiological, and biological data of obese individuals, including population variability, to inform a PBPK framework.MethodsA systematic literature search was performed to collate anatomical, physiological, and biological parameters for obese individuals. Multiple regression analyses were used to derive mathematical equations describing the continuous effect of body mass index (BMI) within the range 18.5–60 kg/m2 on system parameters.ResultsIn total, 209 studies were included in the database. The literature reported mostly BMI-related changes in organ weight, whereas data on blood flow and biological parameters (i.e. enzyme abundance) were sparse, and hence physiologically plausible assumptions were made when needed. The developed obese population was implemented in Matlab® and the predicted system parameters obtained from 1000 virtual individuals were in agreement with observed data from an independent validation obese population. Our analysis indicates that a threefold increase in BMI, from 20 to 60 kg/m2, leads to an increase in cardiac output (50%), liver weight (100%), kidney weight (60%), both the kidney and liver absolute blood flows (50%), and in total adipose blood flow (160%).ConclusionThe developed repository provides an updated description of a population with a BMI from 18.5 to 60 kg/m2 using continuous physiological changes and their variability for each system parameter. It is a tool that can be implemented in PBPK models to simulate drug pharmacokinetics in obese individuals.

Left ventricular diastolic function compared to inferior vena cava diameter variation as predictor of fluid responsiveness in mechanical ventilated patients with shock: The research protocol

Background: Fluid responsiveness, defined as an increase in cardiac output by 15% after a fluid challenge, is recommended to be evaluated in-patients with shock. Left ventricular (LV) diastolic dysfunction is associated with a lower increment of cardiac output after fluid challenge. Despite being a non-invasive test, the echocardiographic evaluation of the left ventricular diastolic function was rarely studied for the prediction of fluid responsiveness. The objective of this study is to evaluate the efficacy of LV diastolic function in predicting fluid responsiveness, comparing with inferior vena cava (IVC) diameter variation method, among shock patients who required mechanical ventilation. Methods: We plan to enroll adult patients with shock admitted to the intensive care unit (ICU). The echocardiographic hemodynamic parameters include IVC diameter variation, peak velocity of early diastolic filling of mitral valve inflow (E wave), peak early diastolic velocity of the mitral valve annulus (Ea), mitral E/Ea ratio, left ventricular ejection fraction (LVEF) and transaortic cardiac output (CO), all at baseline and after fluid therapy are measured. A fluid challenge with an infusion of 300 ml of acetate Ringer’s solution within 15 minutes will be given. Patients who have an increase in systolic blood pressure of at least 10 mmHg, mean arterial pressure of at least 5 mmHg or cardiac output of at least 15% are defined as fluid responders. The primary outcome of this study is the efficacy of the mitral E/Ea ratio comparing with IVC diameter variation in predicting fluid responsiveness. The secondary outcomes include the rate of fluid responsiveness in mechanically ventilated patients and LVEF and CO in patients with shock in the intensive care units. Conclusion: This study will evaluate the efficacy of left ventricular diastolic function measured by the echocardiography (Mitral E/Ea ratio) in predicting fluid responsiveness among mechanical ventilated patients with shock. Trial registrations: Clinicaltrials.gov NCT05066256, registered on January 10th, 2021

The CorInnova Implantable Cardiac Assist System for Direct Cardiac Compression.

The CorInnova cardiac compression device (CorInnova, Inc., Houston, TX, USA) is designed to provide direct biventricular support, increase cardiac output, and improve ventricular unloading in patients with heart failure. Placed within the pericardium and surrounding both ventricles, the device has two concentric sets of thin-film polyurethane chambers: (1) inner (epicardial) saline-filled chambers that conform intimately to the epicardial surface, eradicating any gaps in the interface between the device and the heart; and (2) outer air-filled chambers cycled to provide epicardial compression during systole and negative epicardial pressure during diastole, consistent with physiological cardiac contraction and relaxation. A superelastic, collapsible Nitinol frame gives the device structure, enables minimally invasive self-deployment, and enhances diastolic filling. Preclinical testing has been extremely promising, with improvements in cardiac output and other cardiac parameters in animal heart failure models. This potentially transformative technology is moving rapidly toward first-in-human use. The CorInnova device may provide an effective device-based solution for patients with heart failure who currently have few or limited mechanical cardiac support options, including patients with biventricular cardiac failure, those with right heart failure, those who are older, and those who are of smaller size. It can be removed easily and requires minimal maintenance. An important, unique feature of this technology is that it provides mechanical cardiac assistance without blood contact or need for anticoagulation. The CorInnova device may be particularly important for those patients who have contraindications to anticoagulation due to allergy, neurological bleeds, or preexisting hemorrhage. No other mechanical circulatory support device addresses these underserved heart-failure populations.

INHIBITION OF RAS COMPONENTS ATTENUATES PROGRESSION OF MYOCARDIAL REMODELING IN BOTH NORMOTENSIVE AND HYPERTENSIVE RATS IN EXPERIMENTAL HEART FAILURE

Objective: New findings in the pathogenesis of heart failure (HF) with a focus on extracellular matrix (ECM) and communication in the heart are still relevant for more effective treatment. We focused on signaling pathways involved in cardiac structural remodeling in HF due to pressure and volume overload, as well as on investigating the efficacy of substances with possible antifibrotic potential. Design and method: We used as experimental model 28-week-old hypertensive (TGR) and normotensive (HSD) rats with created aortocaval fistula (ACF), supplemented with ACE inhibitor (ACEi) (Trandolapril, 15 weeks, 6 mg/L) and AT1 receptor blocker (ARB) (Losartan, 15 weeks, 200 mg/L). Results: Echocardiography confirmed an increase in cardiac output and a decrease in ejection fraction in both strains of rats. BW was higher in TGR vs HSD and it was not affected by VO. ACF-induced cardiac volume overload, elevated markers of heart failure and oxidative damage, ANP, BNP-45, and TBARS, were elevated in the blood serum of both strains. ACF induced profibrotic signaling by increasing TGF-, and mRNA collagen I, and collagen I protein expression in the left and right ventricles of HSD rats. In TGR rats ACF decreased TGF- and SMAD2 protein expression in the right ventricle similar to HSD rats, in which ACF also suppressed MMP-2 protein expression. Heart failure affected protein kinase signaling by reducing the protein expression of PKC, PKG, and in part, PKC in both chambers of the heart of both strains. ACF decreased the protein expression of Cx43 and its phosphorylated form, which is significantly proarrhythmic. Hypertension in TGR rats increased mRNA TGF- expression and collagen I, but decreased PKC and PKC protein expression and increased PKC. Conclusions: A notable finding was that the signaling pathways involved in cardiac remodeling were more normalized by the ARB, while proteins involved in intercellular communication, ACEi. The results of analyzes of both experiments indicate attenuated responses of the signaling pathways monitored by us in the heart of hypertensive strains reflecting adaptation to primarily induced pathophysiology. Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 2/0158/19, 2/0002/20

CARDIOPULMONARY TEST PARAMETERS USEFUL FOR ADDRESSING PATIENTS WITH PECTUS EXCAVATUM TO PROMOTION OF PHYSICAL ACTIVITY

Objective: Exercise training increases muscle VO2 by increasing O2 transport and O2 uptake positively affecting cardiac output. In subjects with pectus excavatum cardiac output increase during exercise might be limited by the conformation of the chest. In this condition, the psychological impact of the deformity can further reduce the propensity to physical activity, leading to a sedentary lifestyle. Surgery is the preferred choice in severe cases. However, many patients with milder deformities can benefit from exercise-based treatment. The choice of the therapeutic strategy is fundamental, but the functional parameters on which to base this choice are not yet well defined. Therefore, we investigated the relationships between habitual physical activity and functional physiological parameters obtained from the cardiopulmonary exercise test (exercise performance and stroke volume at peak exercise) in pectus excavatum. Design and method: A cohort of adolescents (15 with pectus excavatum and 15 age- and sex-matched healthy controls) underwent Cardiopulmonary Exercise Test to estimate exercise performance (VO2 max) and stroke volume at peak exercise (VO2/HR, O2 pulse). Habitual weekly physical activity, estimated with International Physical Activity Questionnaire – Short Form (IPAQ-SF), was expressed as METs h-1·week-1. Determinants of exercise performance and stroke volume at peak exercise were investigated in the whole group with multivariable linear regression analysis adjusted for sex, body mass index, forced expiratory volume in the first second, and presence of pectus excavatum. Results: When compared to healthy controls, subjects with pectus excavatum had lower VO2 max (37.2 ± 6.6 vs 45.4 ± 6.4 mL·kg-1·min-1, p < 0.05), and O2 pulse (12.1 ± 2.4 vs 16.2 ± 3.6 mL·min-1·bpm-1, p < 0.05). Importantly, physical activity level was a predictor of VO2 max (B = 0.085; 95% Cl 0.010 to 0.160) while it did not affect O2 pulse (B = 0.035; 95% Cl -0.004 to 0.074). Conclusions: Training programs should be encouraged to increase cardiopulmonary performance in subjects with pectus excavatum. A marked reduction in O2 pulse at peak exercise might be considered as a criteria to address a subject towards surgery.

C72 THE EFFECTS OF BATRIATIC SURGERY ON CARDIO–METABOLIC PROFILE AND CARDIAC REMODELING

Abstract Background Obesity is associated with cardiac remodeling resulting in hypertrophy of the left ventricle (LV) with a predominantly concentric pattern. LV remodeling and fibrosis induce mechanical and electrical dysfunction of the myocardial tissue, an increase in cardiac output, an increase of myocardial workload and mean arterial pressure. Objective To evaluate the impact of bariatric surgery, and therefore of anthropometric and cardio–metabolic variations, on cardiac structure and function. Methods Twenty–six obese patients treated with bariatric surgery were enrolled. All the patients at baseline and at 6 and 12 months underwent a complete anthropometrical evaluation, laboratory determinations and echocardiogram evaluation. The IR has been assessed by HOMA–IR. The patients were divided into two groups: the first group (8 patients) carried out a follow–up at 6 months post–surgery; the second group (18 patients) at 12 months post–surgery. Results As expected, an improvement in the anthropometric and metabolic profile in patients treated with bariatric surgery was observed. Echocardiographic data showed a significant increase in the Ejection Fraction (P < 0.001) and the E/A Ratio (P < 0.001) 6 months after bariatric surgery, a significant reduction in the Interventricular Septum thickness at 6 months (P < 0.001) and at 12 months (P < 0.002) post–surgery and a significant reduction in the Left Ventricular Mass at 6 months (P = 0.02) and at 12 months (P = 0.05) after bariatric surgery. A reduction no significant in the Left Ventricular posterior wall thickness has been observed. Conclusions Our data showed an increase of the systolic function, an increase of the left ventricular diastolic compliance and a reduction in subclinical cardiac organ damage. Therefore, significant weight loss obtained with bariatric surgery may lead to reverse cardiac remodeling, associated with beneficial effects on myocardial structure and systo-diastolic function.

Piezo2 is not an indispensable mechanosensor in murine cardiomyocytes

A short-term increase in ventricular filling leads to an immediate (Frank-Starling mechanism) and a slower (Anrep effect) rise in cardiac contractility, while long-term increased cardiac load (e.g., in arterial hypertension) decreases contractility. Whether these answers to mechanical tension are mediated by specific sensors in cardiomyocytes remains elusive. In this study, the piezo2 protein was evaluated as a potential mechanosensor. Piezo2 was found to be upregulated in various rat and mouse cardiac tissues upon mechanical or pharmacological stress. To investigate its function, C57BL/6J mice with homozygous cardiomyocyte-specific piezo2 knockout [Piezo2-KO] were created. To this end, α-MHC-Cre mice were crossed with homozygous “floxed” piezo2 mice. α-MHC-Cre mice crossed with wildtype mice served as controls [WT-Cre+]. In cardiomyocytes of Piezo2-KO mice, piezo2 mRNA was reduced by > 90% and piezo2 protein was not detectable. Piezo2-KO mice displayed no morphological abnormalities or altered cardiac function under nonstressed conditions. In a subsequent step, hearts of Piezo2-KO or WT-Cre+-mice were stressed by either three weeks of increased afterload (angiotensin II, 2.5 mg/kg/day) or one week of hypercontractility (isoprenaline, 30 mg/kg/day). As expected, angiotensin II treatment in WT-Cre+-mice resulted in higher heart and lung weight (per body weight, + 38%, + 42%), lower ejection fraction and cardiac output (− 30%, − 39%) and higher left ventricular anterior and posterior wall thickness (+ 34%, + 37%), while isoprenaline led to higher heart weight (per body weight, + 25%) and higher heart rate and cardiac output (+ 24%, + 54%). The Piezo2-KO mice reacted similarly with the exception that the angiotensin II-induced increases in wall thickness were blunted and the isoprenaline-induced increase in cardiac output was slightly less pronounced. As cardiac function was neither severely affected under basal nor under stressed conditions in Piezo2-KO mice, we conclude that piezo2 is not an indispensable mechanosensor in cardiomyocytes.

Systemic Cardiovascular Adjustments during Recovery from Passive Heat Stress

Much like exercise, heat stress elicits profound autonomic and hemodynamic responses which may persist in the post‐heating recovery period. In the same way that the post‐exercise recovery period contributes to vascular adaptation with exercise training, the post‐heating recovery period may potentiate beneficial vascular adaptation with chronic heat therapy. In contrast to the well‐studied post‐exercise recovery period, few studies have investigated the systemic cardiovascular adjustments accompanying recovery from whole‐body, passive heat stress. Hypothesis: We hypothesized that mean arterial pressure would be reduced in the post‐heating recovery period due to sustained post‐heating elevations in systemic vascular conductance and despite elevations in cardiac output.MethodsFour subjects (1 F, 27±5 yrs, BMI 26±3 kg/m2) completed two experimental visits (randomized, crossover design) comprising either 60 min of passive heating (HT) or a time‐matched thermoneutral control intervention (TN). Rectal temperature, skin temperature (six sites), brachial blood pressure, cardiac output (open‐circuit acetylene washin method), and heart rate were assessed at baseline, at the end of HT or TN interventions, and for 2 hours of recovery in a 21.4±0.4°C room (REC‐HT/TN). Values are reported as the change in each variable from pre‐intervention baseline and presented as means ± SD. Paired t tests were used to compare responses between conditions.ResultsHeating increased mean body temperature (HT +1.26±0.23°C, TN ‐0.04±0.07°C) (P < 0.001). After 40 min of recovery, mean body temperature tended to remain elevated following heating (HT +0.48±0.18, TN +0.19±0.09°C, P = 0.06). There were no differences in mean body temperature between conditions at 80 min (P = 0.31) or 120 min of recovery (P = 0.37). Mean arterial pressure was reduced at the end of heating (HT ‐12±6, TN +5±4 mmHg, P < 0.01) as elevations in systemic vascular conductance (HT +55±18, TN ‐6±6 mL·min‐1·mmHg‐1, P < 0.01) were not offset by increases in cardiac output (HT +3.5±0.8, TN ‐0.2±0.6 L/min, P < 0.01) sustained by an increased heart rate (HT +40±8, TN ‐2±6 bpm, P < 0.01). Mean arterial pressure tended to remain reduced 40 min into the post‐heating recovery period (REC‐HT ‐6±6, REC‐TN +1±3 mmHg, P = 0.16) due to a tendency for elevations in systemic vascular conductance (REC‐HT +11±21, REC‐TN ‐6±15 mL·min‐1·mmHg‐1, P = 0.08). Cardiac output (REC‐HT +0.5±1.5, REC‐TN ‐0.5±1.1 L/min, P = 0.07) and heart rate (REC‐HT +6±9, REC‐TN ‐3±5 bpm, P = 0.07) also appeared to remain elevated 40 min into the post‐heating recovery period. Mean arterial pressure appeared similar between conditions from 80 minutes of recovery onward (P = 0.85) while systemic vascular conductance (P = 0.12) and cardiac output (P = 0.19) tended to remain elevated. These variables appeared similar between conditions after 120 min of recovery.ConclusionsRecovery from heat stress is marked by sustained hypotension, vasodilation, and elevations in cardiac output and heart rate. These post‐heating recovery responses may facilitate vascular adaptation with heat therapy.

Efficacy of enhanced external counter pulsation in improving six minutes’ walk test in heart failure patients

Introduction and Aim: Enhanced External Counterpulsation (EECP) is an outpatient treatment to improve myocardial perfusion in chronic stable angina patients. We studied the clinical response of heart failure patients' improvement in the functional class and exercise tolerance with EECP. Materials and Methods: We prospectively evaluated twenty-six patients, who had completed a course of EECP with pre and post six minutes’ walk test, functional ability assessed by the New York heart association (NYHA) classification, renal parameters, lipid profile, and diastole to systole(d/s) ratio in terms of Peak amplitude (P) and Area (A) under the curve value. Results: The study group's mean age is of 56 years. The mean left ventricular ejection fraction (LVEF) is 31.44± 5.5%. Patients' demography includes 81% were male, 30% with hypertension (HT),50% with diabetes mellitus (DM), 30%chronic smokers, 61% of them had triple vessel disease (TVD). All the patients improved by a minimum of one NYHA class improvement, Serum urea reduced from 34.37 ± 20.28 to 27.24 ± 18.73 mg/dL (P = 0.002), C-Reactive protein (CRP) reduced from 4.6± 8.0 to 3.76 ± 5.1 mg/dL (P = 0.62). In the measured lipid panel test, only low-density lipoprotein (LDL) reduction from 94.41 ± 38.66 to 80.51 ± 35.09 mg/dL was statistically significant (P =0.03). The six-minute walk test, post-EECP, improved significantly from 340.14 ± 68.5 to 385.5 ± 73.9 meters (P =0.0004). The LVEF increased from 31.44 ± 5.5 to 38.38 ± 8.69 % (P=0.001). Conclusion: EECP treatment significantly improves shortness of breath, six minutes walking distance, and ejection fraction in heart failure patients. The treatment significantly reduces serum urea and LDL level. These positive changes may be due to a sudden increase in cardiac output and hyperdynamic circulation during the treatment.

Effects of Acute Hypobaric Hypoxia Exposure on Cardiovascular Function in Unacclimatized Healthy Subjects: A "Rapid Ascent" Hypobaric Chamber Study.

Background: This study aimed to observe the effects of a fast acute ascent to simulated high altitudes on cardiovascular function both in the main arteries and in peripheral circulation. Methods: We examined 17 healthy volunteers, between 18 and 50 years old, at sea level, at 3842 m of hypobaric hypoxia and after return to sea level. Cardiac output (CO) was measured with Doppler transthoracic echocardiography. Oxygen delivery was estimated as the product of CO and peripheral oxygen saturation (SpO2). The brachial artery’s flow-mediated dilation (FMD) was measured with the ultrasound method. Post-occlusion reactive hyperemia (PORH) was assessed by digital plethysmography. Results: During altitude stay, peripheral oxygen saturation decreased (84.9 ± 4.2% of pre-ascent values; p < 0.001). None of the volunteers presented any hypoxia-related symptoms. Nevertheless, an increase in cardiac output (143.2 ± 36.2% of pre-ascent values, p < 0.001) and oxygen delivery index (120.6 ± 28.4% of pre-ascent values; p > 0.05) was observed. FMD decreased (97.3 ± 4.5% of pre-ascent values; p < 0.05) and PORH did not change throughout the whole experiment. Τhe observed changes disappeared after return to sea level, and normoxia re-ensued. Conclusions: Acute exposure to hypobaric hypoxia resulted in decreased oxygen saturation and increased compensatory heart rate, cardiac output and oxygen delivery. Pre-occlusion vascular diameters increase probably due to the reduction in systemic vascular resistance preventing flow-mediated dilation from increasing. Mean Arterial Pressure possibly decrease for the same reason without altering post-occlusive reactive hyperemia throughout the whole experiment, which shows that compensation mechanisms that increase oxygen delivery are effective.

New Porcine Model of Arteriovenous Fistula Documents Increased Coronary Blood Flow at the Cost of Brain Perfusion.

Background: Arteriovenous fistulas (AVF) represent a low resistant circuit. It is known that their opening leads to decreased systemic vascular resistance, increased cardiac output and other hemodynamic changes. Possible competition of AVF and perfusion of other organs has been observed before, however the specific impact of AVF has not been elucidated yet. Previous animal models studied long-term changes associated with a surgically created high flow AVF. The aim of this study was to create a simple AVF model for the analysis of acute hemodynamic changes. Methods: Domestic female pigs weighing 62.6 ± 5.2 kg were used. All the experiments were held under general anesthesia. The AVF was created using high-diameter ECMO cannulas inserted into femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Near-infrared spectroscopy sensors, flow probes and flow wires were inserted to study brain and heart perfusion. Results: AVF blood flow was 2.1 ± 0.5 L/min, which represented around 23% of cardiac output. We observed increase in cardiac output (from 7.02 ± 2.35 L/min to 9.19 ± 2.99 L/min, p = 0.0001) driven dominantly by increased heart rate, increased pulmonary artery pressure, and associated right ventricular work. Coronary artery flow velocity rose. On the contrary, carotid artery flow and brain and muscle tissue oxygenation measured by NIRS decreased significantly. Conclusions: Our new non-surgical AVF model is reproducible and demonstrated an acute decrease of brain and muscle perfusion.

Mechanism-based strategies to prevent salt sensitivity and salt-induced hypertension.

High-salt diets are a major cause of hypertension and cardiovascular (CV) disease. Many governments are interested in using food salt reduction programs to reduce the risk for salt-induced increases in blood pressure and CV events. It is assumed that reducing the salt concentration of processed foods will substantially reduce mean salt intake in the general population. However, contrary to expectations, reducing the sodium density of nearly all foods consumed in England by 21% had little or no effect on salt intake in the general population. This may be due to the fact that in England, as in other countries including the U.S.A., mean salt intake is already close to the lower normal physiologic limit for mean salt intake of free-living populations. Thus, mechanism-based strategies for preventing salt-induced increases in blood pressure that do not solely depend on reducing salt intake merit attention. It is now recognized that the initiation of salt-induced increases in blood pressure often involves a combination of normal increases in sodium balance, blood volume and cardiac output together with abnormal vascular resistance responses to increased salt intake. Therefore, preventing either the normal increases in sodium balance and cardiac output, or the abnormal vascular resistance responses to salt, can prevent salt-induced increases in blood pressure. Suboptimal nutrient intake is a common cause of the hemodynamic disturbances mediating salt-induced hypertension. Accordingly, efforts to identify and correct the nutrient deficiencies that promote salt sensitivity hold promise for decreasing population risk of salt-induced hypertension without requiring reductions in salt intake.

ERAS Without Intraoperative Goal-Directed Fluid Therapy Is Still ERAS

Acute kidney injury (AKI) occurs in up to 15% of patients after thoracic surgery.1 To mitigate AKI, goal-directed fluid therapy (GDFT) encourages clinicians to manage fluid and volume administration on the basis of objective goals. The key to GDFT is to maximize tissue oxygen delivery without fluid overload by achieving optimal hemodynamic indices. Following a fluid challenge, an increase in cardiac output or stroke volume suggests fluid responsiveness and underlying inadequate intravascular volume.

Maintaining Zone 1 Occlusion is a Dynamic Process: The Effects of Proximal Pressure and Blood Transfusion During REBOA.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) provides hemodynamic support to patients with non-compressible truncal hemorrhage. As cardiac output increases due to aortic occlusion (AO), aortic diameter will increase as a function of compliance, potentially causing unintended flow around the balloon. Swine (N = 10) were instrumented to collect proximal mean arterial blood pressure (pMAP), distal MAP (dMAP), balloon pressure (bP), balloon volume (bV), and distal aortic flow (Qaorta). A 7-Fr automated REBOA catheter was positioned in Zone 1. At T0, animals underwent 30% total blood volume hemorrhage over 30min followed by balloon inflation to complete AO. Automated balloon inflation occurred from T30-T60 when Qaorta was detected. Period of interest was T55-T60, while the balloon actively worked to maintain AO during transfusion of shed blood. Median weight of the cohort was 73.75 [IQR:71.58-74.45] kg. During T40-T55 and T55-T60, median pMAP was 88.95 [IQR:76.80-109.92] and 108.13 [IQR:99.13-119.51] mmHg, P = 0.07. Median Qaorta during T40-T55, and T55-T60 was 0.81 [IQR:0.41-0.96], and 1.53 [IQR:1.07-1.96] mL/kg/min, P = 0.06. Median number of balloon inflations during T40-T55 was 0.00 [IQR:0.00-0.75] and increased during active transfusion to 10.00 [IQR:5.25-14.00], P = 0.001. In clinical practice, following initial establishment of AO, progressive balloon inflations are required to maintain AO in response to intrinsic and transfusion-mediated increases in cardiac output, blood pressure, and aortic diameter.

Impact of head-up tilt on expiratory negative airway pressure ventilation-induced cardiovascular hemodynamics in the halothane-anesthetized intact microminipigs.

Elevation of the head and expiratory negative airway pressure (ENAP) ventilation can both significantly alter cardiovascular hemodynamics. The impact of head-up tilt (HUT) position on mechanically regulated ENAP ventilation-induced hemodynamics was assessed in microminipigs under halothane anesthesia (n = 4) in the absence and presence of adrenergic blockade. Supine ENAP ventilation increased cardiac output, but decreased mean right atrial, systolic pulmonary arterial, and mean left atrial pressures without significantly altering heart rate or aortic pressure. With HUT, the magnitude of ENAP ventilation-induced reduction in right and left atrial pressures was attenuated. HUT minimally altered ENAP ventilation-induced increase in cardiac output and reduction in pulmonary arterial systolic pressure. In addition, with up to 10cm of HUT there was a significant increase in mean right atrial pressure with and without the ENAP ventilation, whereas HUT did not alter the other hemodynamic variables irrespective of ENAP ventilation. These observations suggest that head elevation augments venous return from the brain irrespective of the ENAP ventilation. Additional studies with pharmacological adrenergic blockade revealed that ENAP ventilation-induced increases in cardiac output and decreases in pulmonary systolic pressure were minimally altered by sympathetic nerve activity, irrespective of the head position. However, the observed ENAP ventilation-induced decreases in right and left atrial pressures were largely dependent upon adrenergic activity. These experimental findings may provide insight into future clinical application of HUT and ENAP for patients with head injury and hypotension.

Assessing Cardiac Recovery for Decommissioning of LVAD Support: Structure versus Function

<h3>Introduction</h3> Recovery of left ventricular (LV) function during LVAD support occurs in only 1-3% of patients. Assessment for recovery and LVAD removal is desirable given the risks of infection, stroke, and device malfunction. This case of a patient with an LVAD, with recovered LV systolic function but abnormal exercise hemodynamics, illustrates the potential utility of right heart catheterization studies for clinical decisions. <h3>Case Report</h3> A 35-year-old man presented with cardiogenic shock after a late-presentation ST elevation myocardial infarction, requiring short-term veno-arterial extracorporeal membrane oxygenation post-angioplasty. Then, a HeartMate II LVAD was inserted. Four months after implantation, the patient was well (NYHA I). Serial echocardiography demonstrated recovery of LVEF to 50-55% by 7 months. Repeated hemodynamic assessments were performed over 11 months. Hemodynamics were recorded at supine rest with baseline LVAD speed, with speed reduced to the equivalent of unsupported (8000 rpm) and then during cycle ergometer exercise at a constant work rate (Table). Between baseline and unsupported speeds, minimal change in the mixed venous O2 saturation and smaller increases in mean pulmonary arterial wedge pressure (mPAWP) and mean pulmonary artery pressures (mPAP) were noted during the 3rd and 4th studies. However, during exercise, the patient displayed persistently limited increases in cardiac output (CO) and the relationship between PAWP and CO (∆PAWP/∆CO) was persistently elevated above 2 mmHg/L/min. As such, the patient was listed for transplant rather than explanted. <h3>Summary</h3> Although echocardiographic imaging showed recovery of LV systolic function, exercise at unsupported speed was associated with abnormal ∆PAWP/∆CO, prompting concern of recurrent symptomatic heart failure if the LVAD was explanted. This case illustrates ongoing efforts to evaluate appropriate structural and functional markers of myocardial recovery to support decisions regarding LVAD explantation.

Lower body muscle preactivation and tensing mitigate symptoms of initial orthostatic hypotension in young females.

Initial orthostatic hypotension (IOH) is a form of orthostatic intolerance defined by a transient decrease in blood pressure upon standing. Current clinical recommendations for managing IOH includes standing up slowly or lower body muscle tensing (TENSE) after standing. Considering that IOH is likely due to a large muscle activation response resulting in excessive vasodilation with a refractory period (<2 minutes), we hypothesized that preactivating lower body muscles (PREACT) before standing would reduce the drop in mean arterial pressure (MAP) upon standing and improve presyncope symptoms. The purpose of this study was to provide IOH patients with effective symptom management techniques. Study participants completed 3 sit-to-stand maneuvers, including a stand with no intervention (Control), PREACT, and TENSE. Continuous heart rate and beat-to-beat blood pressure were measured. Stroke volume and cardiac output were then estimated from these waveforms. A total of 24 female IOH participants (mean ± SD: 32 ± 8 years) completed the study. The drops in MAP following PREACT (-21 ± 8 mm Hg; P <.001) and TENSE (-18 ± 10 mm Hg; P <.001) were significantly reduced compared to Control (-28 ± 10 mm Hg). The increase in cardiac output was significantly larger following PREACT (2.6 ± 1 L/min; P <.001) but not TENSE (1.9± 1 L/min; P = .2) compared to Control (1.4 ± 1 L/min). The Vanderbilt Orthostatic Symptom Score following PREACT (9±8 au; P = .033) and TENSE (8 ± 8 au; P = .046) both were significantly reduced compared to Control (14 ± 9 au). Both the drop in MAP and symptoms upon standing improved with either PREACT or TENSE. These maneuvers provide novel symptom management techniques for patients with IOH.

Role of the Air-Blood Barrier Phenotype in Lung Oxygen Uptake and Control of Extravascular Water.

The air blood barrier phenotype can be reasonably described by the ratio of lung capillary blood volume to the diffusion capacity of the alveolar membrane (Vc/Dm), which can be determined at rest in normoxia. The distribution of the Vc/Dm ratio in the population is normal; Vc/Dm shifts from ∼1, reflecting a higher number of alveoli of smaller radius, providing a high alveolar surface and a limited extension of the capillary network, to just opposite features on increasing Vc/Dm up to ∼6. We studied the kinetics of alveolar-capillary equilibration on exposure to edemagenic conditions (work at ∼60% maximum aerobic power) in hypoxia (HA) (PIO2 90 mmHg), based on an estimate of time constant of equilibration (τ) and blood capillary transit time (Tt). A shunt-like effect was described for subjects having a high Vc/Dm ratio, reflecting a longer τ (>0.5 s) and a shorter Tt (<0.8 s) due to pulmonary vasoconstriction and a larger increase in cardiac output (>3-fold). The tendency to develop lung edema in edemagenic conditions (work in HA) was found to be directly proportional to the value of Vc/Dm as suggested by an estimate of the mechanical properties of the respiratory system with the forced frequency oscillation technique.

Effect of Next Generation Pulsatile Mechanical Circulatory Support on Cardiac Mechanics: The PULSE Trial

ObjectivesTo describe hemodynamic effects of iVAC2L mechanical circulatory support (MCS). BackgroundMCS is increasingly used in the context of high-risk percutaneous coronary intervention (PCI). The effect of the pulsatile iVAC2L MCS on left ventricular loading conditions and myocardial oxygen consumption (MVO2) is unknown. MethodsThis prospective single-arm two-center study included 29 patients who underwent high-risk PCI with iVAC2L MCS using simultaneous invasive pulmonary pressure monitoring and left ventricular pressure-volume analysis. Hemodynamic recordings were performed during steady state conditions with MCS off and on before and after PCI. Pressure-volume variations were analyzed to denote responders and non-responders. ResultsThe mean age was 74 (IQR: 70–81) years and the mean SYNTAX score was 31 ± 8.3. Left ventricular unloading with iVAC2L MCS was demonstrated in 22 out of 27 patients with complete PV studies. Patients with moderate or severe mitral regurgitation or presenting with acute coronary syndrome (ACS) had higher filling pressures and volumes and were most responsive to iVAC2L unloading (9/10 patients with moderate or severe MR and 11/11 patients with ACS). Pulsatile MCS activation reduced MAP (−4%), SBP (−9%), ESP (−11%), ESV (−15%) and EDV (−4%) among responders but not among non-responders. Responders experienced significant reductions in afterload (Ea: −19%) with increases in stroke volume (+11%) and cardiac output (+11%). ConclusionsPulsatile iVAC2L MCS in patients with advanced coronary artery disease at high to prohibitive operative risk resulted in LV unloading and reduced myocardial oxygen consumption particularly in patients with ACS or significant MR with higher filling pressures at baseline. Clinical trial registrationNCT03200990.

Role of the Autonomic Nervous System in the Hemodynamic Response to Hyperinsulinemia-Implications for Obesity and Insulin Resistance.

Herein, we summarize recent advances which provide new insights into the role of the autonomic nervous system in the control of blood flow and blood pressure during hyperinsulinemia. We also highlight remaining gaps in knowledge as it pertains to the translation of findings to relevant human chronic conditions such as obesity, insulin resistance, and type 2 diabetes. Our findings in insulin-sensitive adults show that increases in muscle sympathetic nerve activity with hyperinsulinemia do not result in greater sympathetically mediated vasoconstriction in the peripheral circulation. Both an attenuation of α-adrenergic-receptor vasoconstriction and augmented β-adrenergic vasodilation in the setting of high insulin likely explain these findings. In the absence of an increase in sympathetically mediated restraint of peripheral vasodilation during hyperinsulinemia, blood pressure is supported by increases in cardiac output in insulin-sensitive individuals. We highlight a dynamic interplay between central and peripheral mechanisms during hyperinsulinemia to increase sympathetic nervous system activity and maintain blood pressure in insulin-sensitive adults. Whether these results translate to the insulin-resistant condition and implications for long-term cardiovascular regulation warrants further exploration.