Systemic Blood Flow Research Articles

Perioperative management of arteriovenous malformation guided by integrated evaluation of hemodynamics.

We aimed to demonstrate the value of monitoring infants with arteriovenous malformation (AVM) during endovascular embolization with integrated evaluation of hemodynamics (IEH) and guiding decisions according to the underlying pathophysiology. This is a retrospective analysis of the perioperative hemodynamics data for 2 complex cases of AVM transferred to Khaula Hospital in Oman for interventional management. We described the value of novel physiological insights gained from comprehensive IEH and provided a systematic approach to the perioperative management. Postoperative targeted neonatal echo (TNE) was used to guide the weaning of the cardiovascular medications within 24h. Both cases showed significant right ventricle (RV) volume overload before surgery. Narrowing of the pulse pressure (PP) during or after endovascular embolization was used as a marker of compromised systemic blood flow in real time followed by an assessment by TNE to guide the appropriate therapy.Conclusion: Integrated evaluation of hemodynamics is helpful to guide perioperative physiologic-based management of AVM. What is Known: • The preoperative management of hemodynamic compromise due to AVM has been described in many articles. • Perioperative management of AVM and related hemodynamics is a challenge to the intensive care team. What is New: • Integrated evaluation of hemodynamics is a comprehensive assessment and helpful in understanding the underlying physiologic changes during intervention with AVM. • This integrated evaluation can lead to physiologic-based medical recommendation with subsequent improvement.

Fruit-Based Beverages Contain a Wide Range of Phytochemicals and Intervention Targets Should Account for the Individual Compounds Present and Their Availability.

Benefits from micronutrients within fruit juice and smoothies are well documented, but fewer studies research the role of phytochemicals. Well-controlled human studies are essential to evaluate their impact, particularly on glucose and lipid regulation but also gastrointestinal health. Planning these studies requires data on the potential molecular targets. Here we report a comprehensive metabolomic (LC-MS) analysis of the phytochemical composition of four commonly consumed beverages, including data on whether they are free to be absorbed early in the gastrointestinal tract or bound to other plant components. Smoothies contained a wide range of phenolics (free and bound), whereas the fruit juices contained higher amounts of fewer compounds. Orange juice was rich in bound hesperidin (1.97 ± 0.39 mg/100 mL) and hydroxycinnamic acids, likely to be delivered to the colon with the potential to have an impact on gut health. Apple juice contained free chlorogenic acid (3.11 ± 1.03 mg/100 mL), phloridzin (0.40 ± 0.03 mg/100 mL), catechin (0.090 ± 0.005 mg/100 mL), and epicatechin (0.38 ± 0.02 mg/100 mL), suggesting potential roles in glucose uptake reduction or positive effects on systemic blood flow. Redox screening established that differences in chemical composition impacted on bioactivity, highlighting the importance of availability from the matrix. This suggests that fruit-based beverage interventions should target specific mechanisms depending on the fruits from which they are comprised and in particular, the availability of the individual constituents.

Effects of hypoxic gas admixture in functionally univentricular patients awaiting Norwood palliation

Introduction Oxygen delivery in those with functionally univentricular hearts awaiting Norwood palliation depends on a balance between systemic blood flow (Qs) and pulmonary blood flow (Qp). Modulations of pulmonary vascular resistance and systemic vascular resistance can be utilized to help maintain balance between Qp and Qs in a circulation prone to pulmonary overcirculation at the expense of systemic perfusion. While modulating pulmonary vascular resistance using a hypoxic gas admixture (subambient …

Distinct Contribution of Systemic Blood Flow to Hypertension in an African Population Across the Adult Lifespan

Although hypertension in groups of African ancestry is volume-dependent, the relative impact of systemic flow (stroke volume, peak aortic flow [Q]) versus vascular mechanisms (systemic vascular resistance, aortic characteristic impedance [Zc], total arterial compliance) components of arterial load has not been evaluated across the adult age range. In participants of African ancestry (n=824, age=16-99 years, 68.3% female), using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the hemodynamic correlates of age-related increases in blood pressure. Strong independent positive relations between age and stroke volume or peak aortic Q were noted (P<0.0001), effects associated with ventricular end diastolic volume and aldosterone-to-renin ratios. Age-related increases in mean arterial pressure were associated with stroke volume and not systemic vascular resistance. Although age-Q relations began from early adulthood, initially an inverse association between age and aortic Zc (P<0.0001) driven by increments in aortic root diameter (P<0.0001) prevented an enhanced systolic blood pressure and pulse pressure. When Zc began to positively relate to age (P<0.0001), age-Q relations translated into increases in forward wave pressures and hence systolic blood pressure and pulse pressure. Age relations with pulse pressure were as strongly determined by Q as by Zc or total arterial compliance (0.027±0.001 versus 0.028±0.001 and 0.032±0.003 mm Hg per yearly increase in pulse pressure produced by Q, Zc, and total arterial compliance; P<0.0001). Uncontrolled hypertension (confirmed with 24-hour blood pressure) was determined more by Q, Zc, and total arterial compliance than by increases in systemic vascular resistance (P<0.0005 for comparison). In conclusion, relationships between age and systemic blood flow contribute markedly to hypertension in groups of African origins.

Decreased Pulmonary Arterial Compliance is a Predictor for Poor Outcomes in Infants with Isolated Atrial Septal Defect and Pulmonary Hypertension.

This study aimed to investigate risk factors for poor outcomes in infants with isolated atrial septal defect (ASD) and pulmonary hypertension who had unexpectedly fatal course. We retrospectively reviewed 22 infants with isolated ASD and pulmonary hypertension, and analyzed the relationship between clinical outcomes and pulmonary hemodynamic parameters including pulmonary arterial resistance (Rp) and compliance (Cp) based on cardiac catheterization among them. Age and weight at cardiac catheterization were 5 (1-11) months and 4.9 (3.1-9.2) kg, respectively. There were 17 individuals with Down syndrome. Pulmonary hemodynamic parameters were shown as follows: the ratio of pulmonary to systemic blood flow: 2.0 (0.6-3.8), mean pulmonary arterial pressure: 41 (20-60) mmHg, the ratio of pulmonary to systemic mean pressure (Pp/Ps): 0.67 (0.46-1.13), Rp: 4.11 (0.68-15.80) Wood unitsm2, and Cp: 1.80 (0.63-6.16) mL/mmHgm2. There were 4 deaths during the follow-up period of 40 (7-241) months. Univariable logistic regression analysis revealed that Pp/Ps (odds ratio [OR]: 18,500, 95% confidential interval [CI] 1.48-230,659,690, P = 0.041) and Cp (OR: 0.03, 95% CI 0.001-0.73, P = 0.031) were significantly related to death. A Pp/Ps cutoff value more than 0.94 and a Cp cutoff value less than 0.97mL/mmHgm2 yielded as the predictors of death with sensitivity of 98% and 94%, specificity of 75% and 75%, respectively. Decreased Cp is a previously unrecognized predictor for poor outcome in infants with isolated ASD and pulmonary hypertension.

TO FIND OUT CORRELATION BETWEEN SVC FLOW AND LEFT VENTRICULAR OUTPUT IN NEWBORN BETWEEN GESTATIONAL AGE OF 34-37 WEEKS AND >37 WEEKS ON LIFE DAY ONE

Background: Preterm newborn is vulnerable to brain injury which is thought to be caused partly by abnormalities in cerebral perfusion (1). Commonly used parameters such as blood pressure &amp; blood lactate level are not sufficient to detect low circulatory blood flow in preterm neonate because these are poor surrogate markers of systemic blood flow during the circulatory transition just after birth Methods- The Present Prospective Cross sectional observational study was conducted in the department of Paediatrics, attached to DR.SN Medical College Jodhpur over the duration of one year .Ethical consent was taken from local institutional ethical committee of Dr.S.N Medical College Jodhpur.&#x0D; Results: In present study 2D Echocardiography was done in preterm newborn (Median gestational age 35 week) (range 34-37 week ) on life day one for measurement of superior vena cava blood flow in which mean flow was 62.5±20.93 ml/kg/min (Mean±SD) and Median flow was 57.83ml/kg/min and range of SVC flow was 18-143 ml/kg/min. Also measured left ventricular output on life day one in which Mean±SD and median LVO flow was 204.88±70.74 and 189.5 which show r value 0.56 with significant positive predictive value &lt;0.0001 by Pearson’s correlation coefficient. In term newborn between gestational ages of 37-41 week with Median gestational age 39 week (range 37-41 week) on life day one. In which mean LVO flow was 203.31± 61.88 (Mean±SD) and mean SVC flow was 58.89±19.11, (Mean±SD) Shows r value 0.40 and positive predictive value &lt; 0.002 by using Pearson’s correlation coefficient.&#x0D; Conclusion: We conclude that SVC flow measurent through 2D colour Doppler echocardiography is most reliable and non-invasive method in preterm newborn as well as evaluation of treatment. . Although echocardiographic assessment of LVO appears to be relatively robust, it is of limited clinical value preterm neonates in the neonatal unit setting because the majority of sick preterm neonate will have patent ductus arteriosus, meaning that LVO does not represent systemic blood flow and is in fact a better marker of pulmonary flow volume.&#x0D; Keywords: SVC, Preterm, Term neonates.

Regional perfusion monitoring in shock.

Despite restoration of adequate systemic blood flow in patients with shock, single organs may remain hypoperfused. In this review, we summarize the results of a literature research on methods to monitor single organ perfusion in shock. We focused on methods to measure heart, brain, kidney, and/or visceral organ perfusion. Furthermore, only methods that can be used in real-time and at the bedside were included. We identified studies on physical examination techniques, electrocardiography, echocardiography, contrast-enhanced ultrasound, near-infrared spectroscopy, and Doppler sonography to assess single organ perfusion. Physical examination techniques have a reasonable negative predictive value to exclude single organ hypoperfusion but are nonspecific to detect it. Technical methods to indirectly measure myocardial perfusion include ECG and echocardiography. Contrast-enhanced ultrasound can quantify myocardial perfusion but has so far only been used to detect regional myocardial hypoperfusion. Near-infrared spectroscopy and transcranial Doppler sonography can be used to assess cerebral perfusion and determine autoregulation thresholds of the brain. Both Doppler and contrast-enhanced ultrasound techniques are novel methods to evaluate renal and visceral organ perfusion. A key limitation of most techniques is the inability to determine adequacy of organ blood flow to meet the organs' metabolic demands.

Foramen ovale and ductus arteriosus hemodynamics in Dextro Transposition of Great Arteries (D-TGA) with intact ventricular septum, case report, and literature review

D-TGA is characterized by discordant Ventriculo-arterial connection. For the patient to survive there should be a mixing of the oxygenated and deoxygenated blood at the atrial, ventricular and/or the great vessel level. The hemodynamics of the PFO and ductus arteriosus in D-TGA with intact ventricular septum (VS) is complex and depends upon the relative difference between the pulmonary and systemic vascular resistance as well as the ventricular compliance. D-TGA with intact VS might be associated with persistent pulmonary hypertension as well as with low pulmonary vascular resistance leading to changes in the hemodynamics and direction of flow through the PDA and/or the PFO. The indications of balloon atrial septestomy as well as the initiation and/or the continuation of Prostaglandin infusion are conflicting issues in such cases. We are presenting a case of D-TGA with intact VS who developed steeling and signs of low systemic blood flow because of a large PDA. We reviewed the hemodynamics of PFO and DA in such cases as well as the indications of BAS and PG infusion.

Morphogenesis of Penile Cavernous Fibrosis in Hypotestosteronemia: an Experimental Study

Introduction. Erectile dysfunction is a multifactorial condition that is the inability to achieve or maintain an erection sufficient for sexual intercourse. The classic method for studying the fundamental aspects of erectile reactions in normal and pathological conditions, as well as creating new methods of treatment, is experimental animal models used in preclinical studies. However, for more than 30 years of studying this problem in experimental researches, the specific moment of occurrence of morphological alterations in the cavernous bodies of the penis has not been established. In addition, the choice of the time frame of the developed therapeutic effects on the penis is not substantiated and differs for various authors, which indicates the lack of validity of their results.Purpose of the study. To determine the features of morphological alterations and the severity of fibrogenic pathological process in the cavernous bodies of the penis in the time dynamics of experimental modeling of hypotestosteronemia.Materials and methods. Laboratory animals is 20 white male rabbits, «New Zealand» breed, Oryctolagus cuniculus genus. Penile cavernous fibrosis in rabbits was induced by hypotestosteinemia due to bilateral orchiectomy. The level of total testosterone in the systemic blood flow in laboratory animals was determined on 1, 2, 3, 14, 21, and 28 days. Biopsies of penile tissues were evaluated by pathomorphological examination (Hematoxylin-eosin, Masson’s trichrome, Weigert’s staining, and light microscopy). Statistical processing of the obtained data was performed using Microsoft Excel and «Statistica 10.0» programs using the Student`s T-criteria.Results. Castration of rabbits leads to a 10-fold decrease in blood testosterone levels after 1 day after castration. Testosterone deficiency occurs by day 28. Morphological signs of the restructuring of smooth muscle cells, sinuses and connective tissue structures in the cavernous bodies of the penis are clearly defined by the day 7 after castration. Severe fibrotic changes in the cavernous tissues of the penis were noted at day 28.Conclusion. Thus, the obtained data demonstrate the dynamics of morphological alterations in penile tissues as early as 7 days after inducing hypotestosteronemia, which indicates the need to revise the time frame of therapeutic effects in studies using the castration animal model of erectile dysfunction.

ABERNATHY MALFORMATIONS IN CHILDREN. EXPERIENCE IN ENDOVASCULAR AND SURGICAL TREATMENT

Introduction. Congenital portosystemic shunt (SPSS) is a congenital anomaly of the portal system. Blood from the portal system, bypassing the hepatic bloodstream, enters the systemic venous bloodflow. Clinical manifestations are not specific. SPSS can be suspected in patients with arterial hypoxemia and intrapulmonary vascular dilatation, in patients with foci of nodular hyperplasia in the liver, with carbohydrate metabolism disorders in the form of hyperinsulinemia and hypoglycemia, hepatic encephalopathy, hyperammoniemia. Material and methods. Nine patients ( five boys and four girls) , aged 7.7 ± 5.2, were treated in our clinic. All patients had hyperammonemia before surgery 124.5 ± 24.7 μmol / L. Five patients had endovascular SPSS occlusion. Four patients had open SPSS ligation. Results. An immediate technical success was achieved in all patients. There were no complications after endovascular treatment. There was one relapse which required a repeated endovascular occlusion. After endovascular occlusion, the length of hospital stay was shorter, postoperative period was much easier; there were no serious complications compared with the open SPSS ligation. Blood ammonia returned to normal levels in eight patients. In one patient who had multiple shunts and incomplete occlusion, blood ammonia level decreased by twice, up to 82 μmol / L. Conclusion. If SPSS is revealed, a surgical intervention is recommended to separate the portal and systemic venous blood flow. In the surgical treatment for SPSS, X-ray surgical endovascular occlusion is more preferable. If this technique was not possible, surgeons performed open surgical intervention.

The Natural and Unnatural History of Ventricular Septal Defects Presenting in Infancy: An Echocardiography-Based Review

Ventricular septal defect (VSD), the most common congenital heart defect, accounts for 40% of heart malformations. Despite this prevalence, there remains no consensus on the utility of echocardiography to guide modern-era treatment. In this study, we evaluated patients with isolated VSDs to test the hypothesis that echocardiographic evidence of left ventricular (LV) volume overload and type of VSD are associated with surgical intervention and to identify useful echocardiographic indicators for management of VSDs in infants and children. We reviewed 350 patients with VSDs diagnosed during the first year of life. Echocardiographic measurements were made at the time of diagnosis and at the endpoint. The VSD area was calculated using inner edge to inner edge dimensions obtained from two planes and indexed to body surface area. Aortic annulus dimension, left atrium to aortic root ratio, LV end-diastolic diameter, left atrial volume, VSD velocity-time integral, ejection fraction, and pulmonary to systemic blood flow ratio (Qp:Qs) were measured using conventional methods. One hundred seventy-seven muscular (50.5%) and 162 perimembranous (46%) VSDs accounted for the vast majority of defects. Only seven (4%) muscular defects required surgical closure, while 76 (47%) perimembranous defects required surgery. Indexed VSD area, VSD to aortic valve ratio, indexed left atrium volume, LV end-diastolic diameter, VSD velocity-time integral, and Qp:Qs at diagnosis were significantly different between the surgical and nonsurgical groups. Ventricular septal defect area > 50mm2/m2 at initial diagnosis was independently associated with risk for surgery (P=.0055). Indexed VSD area is an echocardiographic variable that can be easily measured at diagnosis and can provide insight into the likelihood of requiring surgical intervention regardless of the type and location of the defect.

Evaluation of Central Line Thrombosis in Children with Heart Failure on Continuous Infusion Milrinone

Milrinone is utilized for hemodynamic support in heart failure (HF) patients. Due to reduced cardiac output and systemic blood flow, patients with HF are at increased risk of thrombosis. Central venous catheter (CVC) placement compounds this risk. The aim of this study was to determine the incidence of thrombosis, identify thrombosis risk factors, and determine the impact of anticoagulation in pediatric patients receiving continuous milrinone via CVC at the Medical University of South Carolina. This retrospective study evaluated HF patients less than 18 years of age receiving continuous milrinone infusion via CVC for greater than or equal to 14 days between July 2014 and July 2019. Patients were evaluated based on anticoagulation (AC) status: therapeutic, prophylactic, or none (NAC). The primary outcome measure was the incidence of thrombosis. Possible risk factors for thrombus formation analyzed included age, pathogenesis of heart failure, ventricular assist device (VAD) use, duration of milrinone, and type of CVC. Blood product, factor VII, and prothrombin complex concentrate (PCC) utilization during VAD placement and transplant were analyzed as safety endpoints. A total of 35 patients were included - 16 patients receiving AC and 19 with NAC. There was no difference in thrombus formation between the AC and NAC groups [5 vs. 6; P = .49]. Of patients on prophylactic AC, 50% (n = 4) experienced a thrombus, compared to 25% (n = 12) of patients on therapeutic AC. Patients with CVC in place for greater than 300 days had an incidence of thrombosis of 83% (n = 6). Those receiving therapeutic AC used more PCC and Factor VII than the NAC group during transplant [17.37 units/kg vs. 0, P = .004, 74.74 mcg/kg vs. 18 mcg/kg, P = .025]. Those on therapeutic AC utilized more blood products than patients on prophylactic AC during both VAD placement and transplant (61.5 mL/kg vs. 3.5 mL/kg, P = .003) and NAC patients (61.5 mL/kg vs 24.6 mL/kg, P = .046). Incidence of thrombosis was similar among anticoagulated and non-anticoagulated patients who were on continuous infusion milrinone. Higher total CVC days increased the risk of thrombosis. Prophylactic anticoagulation had a limited effect on thrombus formation, but did not increase blood product use during VAD and transplant procedures as compared to therapeutic anticoagulation.

Percutaneous Impella Device for Mechanical Circulatory Support in Children with Cardiogenic Shock: Long Term Outcomes

Use of temporary mechanical circulatory support (MCS) is an alternative to increase systemic blood flow avoiding the possible cardiotoxicity and long-term morbidity of inotropes and vasopressors. It is often the only option to achieve hemodynamic stability. Use of temporary MCS is increasing in frequency in children with evolution of new technologies. Recently, catheter deployed micro-axial percutaneous ventricular assist device (PC-VAD) has been approved for management of cardiogenic shock in adults. We present our experience and long-term outcomes associated with use of this device in a pediatric cardiac intensive care unit at a freestanding children's hospital. All patients treated for cardiogenic shock with PC-VAD alone between September 2014 and June 2019 were included in retrospective analysis. The device sizes used included CP device which provides up to 4.0 l/min of flow and 5.0 device which provides 5.0 l/min of flow. Demographic and support data were reviewed and reported using descriptive statistics. A total of 24 PC-VAD devices were implanted in 18 patients: CP (n=17), and 5.0 (n=7). Median patient age was 17 years (IQR 15,20), weight of 61 kg (IQR 54,75), and BSA of 1.72 m2(IQR 1.58,1.96). Median length of CP support was 5 days (IQR 4,7) and 5.0 was 12 days (IQR 11,22). The most common device related complications included site bleeding 9/24 (38%), ventricular arrhythmias 3/24 (17%) and extremity arterial thrombus 1/24 (4%), with no limb ischemia encountered. Acute renal failure requiring CRRT occurred in 5/18 (38%) patients. None of the patients sustained neurologic injury. Median ICU length of stay was 24 days (IQR 15,45) with median hospital length of stay of 35 days (26,80). The survival to ICU discharge was 89% (16/18) and survival to hospital discharge was 89% (16/18). Twelve out of eighteen (67%) patients were alive at one year. Temporary MCS for cardiogenic shock with PC-VAD shows favorable short and long-term outcomes in select pediatric patients. This type of circulatory support can be considered for management of older children with acute cardiogenic shock to achieve quicker hemodynamic stability, end-organ recovery and as a temporary bridge to recovery or clinical decision making. The risk profile in our population was low and only minor complications occurred during the treatment.

Exercise intolerance in heart failure: The important role of pulmonary hypertension

What is the topic of this review? This review concerns the negative impact of pulmonary hypertension (PH) on the pulmonary haemodynamic and gas exchange responses to exercise, considering the mechanisms by which PH plays a role in exercise intolerance in heart failure (HF) patients. What advances does it highlight? The hallmark limited pulmonary vascular 'reserve' and impaired pulmonary gas exchange responses to exercise in HF are worsened by the development of PH; these are key determinants of exercise intolerance. Even HF patients who present with 'normal' pulmonary vascular function experience exercise-induced PH, which plays a role in exercise intolerance. Patients with heart failure universally complain of exertional intolerance, but the underlying cause(s) of this intolerance may differ between patients with different disease phenotypes. Exercise introduces an impressive stress to the lungs, where elevations in venous return and cardiac output engender substantial increases in pulmonary blood volume and flow. Relative to healthy individuals, the pulmonary vascular reserve to accept this increase in pulmonary perfusion is compromised in heart failure, with a growing body of evidence suggesting that the development of pulmonary hypertension (PH), and in particular a precapillary component of PH, worsens the pulmonary haemodynamic response to exercise in these patients. Characterized by an exaggerated increase in pulmonary arterial pressure and an elevation in pulmonary vascular resistance, this dysfunctional pulmonary haemodynamic response plays a role in exercise intolerance, probably through an impairment of right ventricular function, underperfusion of the pulmonary circulation and a subsequent reduction in systemic blood flow and oxygen delivery. The hallmark abnormalities in ventilatory and pulmonary gas exchange that accompany heart failure, including a greater ventilatory equivalent for carbon dioxide, are also worsened by the development of PH. This raises the possibility that measures of exercise pulmonary gas exchange might help to 'describe' underlying PH in heart failure; however, several fundamental issues and questions need to be addressed before such gas exchange measures could truly be considered efficacious measures used to differentiate the type of PH and track the severity of PH in heart failure. exercise intolerance, heart failure, pulmonary gas exchange, pulmonary haemodynamics, pulmonary hypertension.

What determines systemic blood flow in vertebrates?

In the 1950s, Arthur C. Guyton removed the heart from its pedestal in cardiovascular physiology by arguing that cardiac output is primarily regulated by the peripheral vasculature. This is counterintuitive, as modulating heart rate would appear to be the most obvious means of regulating cardiac output. In this Review, we visit recent and classic advances in comparative physiology in light of this concept. Although most vertebrates increase heart rate when oxygen demands rise (e.g. during activity or warming), experimental evidence suggests that this tachycardia is neither necessary nor sufficient to drive a change in cardiac output (i.e. systemic blood flow, Q̇sys) under most circumstances. Instead, Q̇sys is determined by the interplay between vascular conductance (resistance) and capacitance (which is mainly determined by the venous circulation), with a limited and variable contribution from heart function (myocardial inotropy). This pattern prevails across vertebrates; however, we also highlight the unique adaptations that have evolved in certain vertebrate groups to regulate venous return during diving bradycardia (i.e. inferior caval sphincters in diving mammals and atrial smooth muscle in turtles). Going forward, future investigation of cardiovascular responses to altered metabolic rate should pay equal consideration to the factors influencing venous return and cardiac filling as to the factors dictating cardiac function and heart rate.

In vitro and computational modelling of drug delivery across the outer blood-retinal barrier.

The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate the development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion, due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer blood-retinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary in vitro and in silico models to study drug transport from silicone oil across the OBRB. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics software and validated using independent in vitro datasets. Computational simulations were able to predict dextran movement and ibuprofen release, with all of the features of the experimental release profiles being observed in the simulated data. Simulated values for peak concentrations of permeated dextran and ibuprofen released from silicone oil were within 18% of the in vitro results. This model could be used as a predictive tool for drug transport across this important tissue.

Estimation of intracardiac shunts in young children with a novel indicator dilution technology

Clinical evaluation of intracardiac shunts in children is not straightforward. Echocardiography can only diagnose the presence of a shunt but does not estimate the shunt ratio. This can be a critical factor that influences treatment options. In this single-center, prospective, observational, method-comparison study, we validate the ability of a novel monitoring device COstatus to estimate the intracardiac shunt ratio (Qp/Qs) of pulmonary (Qp) to systemic (Qs) blood flow in young children before and after corrective cardiac surgery. The indicator dilution technology COstatus monitor was compared to two other more invasive reference techniques, perivascular ultrasonic flow probes (placed around the pulmonary truncus and ascending aorta) and the oximetric shunt equation (using arterial and venous blood gases). Our study revealed that the COstatus monitor detected intracardiac shunts with high sensitivity and specificity but there was some underestimation of the shunt ratios compared to the reference techniques.

Cardiac remodeling and factors determining occurrence of atrial arrhythmia after surgical closure of atrial septal defect in adults

The purpose of this study was to assess cardiac remodeling and to determine factors predicting the occurrence of atrial arrhythmia after surgical closure of atrial septal defect (ASD) in adults. Retrospective study including 33 adult patients (> 20 years old, mean age: 34 ± 11 years, 26 women) who underwent surgical closure of secundum or sinus venosus ASD. Before operation, all patients had dyspnea and 15% were in NYHA III-IV. Sinus rythm was present in 85% of patients. The ratio of pulmonary to systemic blood flow was calculated, yielding a mean of 2.8 + − 1 and pulmonary artery hypertension (PAH) was observed in 80% of patients with a mean value of 41.3 ± 10 mmHg. The ASD were closed by pericardial or Dacron patch in 97% of cases. Operative death was observed in 2 cases. In survival patient, with a follow-up of 97 + 57 months, regression of right ventricular dilatation and PAH occurred in the first post-operative month and was maintained at late follow-up. Atrial arrhythmia occurred in 5 patients and were determined by older operative age ( P = 0.003) and the absence of cardiac remodelling after surgery. surgical correction of ASD in adults is safe and efficacious. Cardiac remodelling after ASD closure in the adult is a common and an early event and prevents late morbidity, which is in most cases due to arrhythmias. The mode of closure does not seem to significantly impact remodelling.

Forward blood flow provoked by changing intravascular pressure using an extracorporeal circulation during cardiopulmonary resuscitation

Since both “cardiac pump” and “thoracic pump” theories have been proved during cardiopulmonary resuscitation (CPR), the mechanism of forward blood flow during closed chest compression still remains open to question. The cardiac pump seems to work by the direct compression of the cardiac ventricles between the sternum and vertebral column. A pressure gradient created between the ventricle and aorta generates systemic blood flow. However, the thoracic pump mechanism presumes chest compression causes a rise in intrathoracic pressure which generates a blood flow from the thoracic cavity to the systemic circulation. Retrograde blood flow from the right heart into the systemic veins is prevented by a concomitant collapse of veins at the thoracic inlet. We hypothesize that the intrinsic decrease of vascular resistance from the aorta to peripheral arteries and the existence of competent venous valves enable blood to flow unidirectionally by the fluctuation of intravascular pressures during closed chest compression. The purpose of this study is to prove an antegrade arterial blood flow without cardiac compression and intrathoracic pressure changes in an animal cardiac arrest model. We demonstrate that arterial pulses can be developed by using an extracorporeal circuit, resulting in forward blood flow from the aorta through the systemic vasculature. It can be suggested that changes in intravascular pressure provoked by either cardiac or thoracic pump generate systemic blood flow during closed chest compression, while systemic vascular patency and valve function may be required for successful CPR.

Effect of Ischemic Postconditioining on Change of Immunoreactivity Level to PECAM-1/CD31 in Rat Neocortex Structures after Global Brain Ischemia

Introduction. Ischemic postconditioning (IPostC) of the brain can be considered as a promising approach to limit reperfusion injury in the ischemic area of the brain. Objective – to study the effect of IPostC after global cerebral ischemia on the level of immunoreactivity to PECAM-1/CD31 in the structures of layers II, III and V of the neocortex of rats at different periods of the reperfusion period.Material and methods. In male Wistar rats, a 10-minute global cerebral ischemia was modeled followed by IPostC in the form of reperfusion-ischemia at 15sec/15sec. In the early (2 days) and late (7 days) reperfusion periods after damaging ischemia, the number of morphologically unchanged neurons and the level of immunoreactivity to PECAM-1/CD31 in the structures of layers II, III and V of the neocortex were estimated.Results. It is shown that the use of IPostC by 2 days of reperfusion contributed to the increase in the number of unchanged neurons in layers II and III of 25.8 and 28.2 % (P&lt;0.05), which was not accompanied by changes in the level of immunoreactivity to PECAM-1/CD31, to 7 days of reperfusion there was an increase in the number of unchanged neurons in layers II, III and V of 19.2, 22,1, 21,4 % (P&lt;0.05) was observed a decrease in the level of immunoreactivity to PECAM-1/CD31 in the structures of these layers of 27.4, 39.4, and 16.7 % (P&lt;0.05), respectively, when compared with similar indicators in groups without the use of IPostC.Conlusions. In the mechanisms of physiological reaction formed in the application of ischemic postconditioning after cerebral ischemia and leading to the preservation of the number of unchanged neurons in the late reperfusion period involved PECAM-1/CD31, which suggests that the protective potential of the phenomenon is realized by possible inhibiting the migration of neutrophils, monocytes and lymphocytes and extravasation of leukocytes from the systemic blood flow into the damaged area of the brain, i.e. through suppression of inflammatory response.