Distribution Of Cardiac Output Research Articles

A Multiscale Mathematical Model for the Fetal Blood Circulation of the Second Half of Pregnancy.

Doppler ultrasound is a commonly used method to assess hemodynamics of the fetal cardiovascular system and to monitor the well-being of the fetus. Indices based on the velocity profile are often used for diagnosis. However, precisely linking these indices to specific underlying physiology factors is challenging. Several influences, including wave reflections, fetal growth, vessel stiffness, and resistance distal to the vessel, contribute to these indices. Understanding these data is essential for making informed clinical decisions. Mathematical models can be used to investigate the relation between velocity profiles and physiological properties. This study presents a mathematical model designed to simulate velocity wave propagation throughout the fetal cardiovascular system, facilitating the assessment of factors influencing velocity-based indices. The model combines a one-fiber model of the heart with a 1D wave propagation model describing the larger vessels of the circulatory system and a lumped parameter model for the microcirculation. Fetal growth from 20 to 40 weeks of gestational age is incorporated by adjusting cardiac and circulatory parameter settings according to scaling laws. The model's results, including cardiac function, cardiac output distribution, and volume distribution, show a good agreement with literature studies for a growing healthy fetus from 20 to 40 weeks. In addition, Doppler indices are simulated in various vessels and agree with literature as well. In conclusion, this study introduces a novel closed-loop 0D-1D mathematical model that has been verified against literature studies. This model offers a valuable platform for analyzing factors influencing velocity-based indices in the fetal cardiovascular system.

LUV Score - a combination of bedside lung ultrasound and velocity-time integral (VTI) to predict mortality risk in STEMI patients

Abstract Background Early risk stratification is essential for in-hospital management of ST-segment–elevation myocardial infarction (STEMI). Development of acute heart failure and pulmonary edema is associated with poorer prognosis in this setting. Velocity–time integral (VTI) estimates stroke volume and cardiac output and has never been tested in acute coronary syndromes. Purpose Our aim was to evaluate the prognostic ability of a novel cardiothoracic ultrasound protocol for hemodynamic assessment with lung ultrasound (LUS) and VTI in patients with STEMI. Methods LUS and VTI were performed within 24h of admission for STEMI. LUS consisted of 8 scanning zones. A LUS combined with VTI (LUV) classification was developed. Receiver operating characteristic (ROC) analyses were performed to assess LUV score with in-hospital mortality, and it was compared with traditional Killip classification. Results From September 2022 and January 2023, 104 consecutive patients were admitted with ST-segment–elevation myocardial infarction. Fifteen patients were excluded from the analysis because were not assessed within 24h of admission. Therefore, 89 patients were included in the final analysis. Mean age was 62 years, 59% were male, 55% had hypertension, 32% had diabetes, 43% was anterior wall myocardial infarction and 16% had Killip 3 or 4 at admission. Overall in-hospital mortality was 7.9% and mortality across LUV categories were 0%, 0%, 8% and 50% for LUV A-D, respectively. A VTI ≥ 14 implied a negative predictive value for in-hospital mortality of 100%. The area under the ROC curve of LUV classification for in-hospital mortality was 0.92 (P=0.001), and Killip classification (0.85, P<0.001; P=0.48 for the difference between curves – Figure 1). Incidences of culprit vessel according to LUV categories are illustrated at Figure 2. There were no left main culprit vessel in our sample. The distribution of Cardiac Output (CO) and Cardiac index (CI) and Cardiac Power Output (CPO) were the following: LUV A: CO = 4.5 (1.2), CI = 4.0 (1.1) CPO = 0.9 (0.3); LUV B CO = 3.8 (0.9) CI = 3.4 (0.8) CPO = 0.7 (0.2); LUV C CO = 3.3 (0.8) CI = 3.0 (0.8) CPO = 0.6 (0.1) ; LUV D CO = 2.9 (0.7) CI = 2.7(0.5) CPO = 0.5(0.1). Conclusions In a cohort of patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, LUV score provided an excellent AUC for prediction of in-hospital mortality. LUV score is an easy, noninvasive, rapidly acquired, and accurate method for risk stratification in STEMI patients.

A large arteriovenous fistula steals a considerable part of systemic blood flow during veno-arterial extracorporeal circulation support in a porcine model.

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is one of the most frequently used mechanical circulatory support devices. Distribution of extracorporeal membrane oxygenation flow depends (similarly as the cardiac output distribution) on regional vascular resistance. Arteriovenous fistulas (AVFs), used frequently as hemodialysis access, represent a low-resistant circuit which steals part of the systemic perfusion. We tested the hypothesis that the presence of a large Arteriovenous fistulas significantly changes organ perfusion during a partial and a full Veno-arterial extracorporeal membrane oxygenation support. Methods: The protocol was performed on domestic female pigs held under general anesthesia. Cannulas for Veno-arterial extracorporeal membrane oxygenation were inserted into femoral artery and vein. The Arteriovenous fistulas was created using another two high-diameter extracorporeal membrane oxygenation cannulas inserted in the contralateral femoral artery and vein. Catheters, flow probes, flow wires and other sensors were placed for continuous monitoring of haemodynamics and organ perfusion. A stepwise increase in extracorporeal membrane oxygenation flow was considered under beating heart and ventricular fibrillation (VF) with closed and opened Arteriovenous fistulas. Results: Opening of a large Arteriovenous fistulas (blood flow ranging from 1.1 to 2.2L/min) resulted in decrease of effective systemic blood flow by 17%-30% (p < 0.01 for all steps). This led to a significant decrease of carotid artery flow (ranging from 13% to 25% after Arteriovenous fistulas opening) following VF and under partial extracorporeal membrane oxygenation support. Cerebral tissue oxygenation measured by near infrared spectroscopy also decreased significantly in all steps. These changes occurred even with maintained perfusion pressure. Changes in coronary artery flow were driven by changes in the native cardiac output. Conclusion: A large arteriovenous fistula can completely counteract Veno-arterial extracorporeal membrane oxygenation support unless maximal extracorporeal membrane oxygenation flow is applied. Cerebral blood flow and oxygenation are mainly compromised by the effect of the Arteriovenous fistulas. These effects could influence brain function in patients with Arteriovenous fistulas on Veno-arterial extracorporeal membrane oxygenation.

Effects of Arterial Carbon Dioxide Tension on Cerebral and Somatic Regional Tissue Oxygenation and Blood Flow in Neonates After the Norwood Procedure With Deep Hypothermic Cardiopulmonary Bypass.

Neonates undergoing the Norwood procedure for hypoplastic left heart syndrome are at higher risk of impaired systemic oxygen delivery with resultant brain, kidney, and intestinal ischemic injury, shock, and death. Complex developmental, anatomic, and treatment-related influences on cerebral and renal-somatic circulations make individualized treatment strategies physiologically attractive. Monitoring cerebral and renal circulations with near infrared spectroscopy can help drive rational therapeutic interventions. The primary aim of this study was to describe the differential effects of carbon dioxide tension on cerebral and renal circulations in neonates after the Norwood procedure. Using a prospectively-maintained database of postoperative physiologic and hemodynamic parameters, we analyzed the relationship between postoperative arterial carbon dioxide tension and tissue oxygen saturation and arteriovenous saturation difference in cerebral and renal regions, applying univariate and multivariate multilevel mixed regression techniques. Results were available from 7,644 h of data in 178 patients. Increases in arterial carbon dioxide tension were associated with increased cerebral and decreased renal oxygen saturation. Differential changes in arteriovenous saturation difference explained these effects. The cerebral circulation showed more carbon dioxide sensitivity in the early postoperative period, while sensitivity in the renal circulation increased over time. Multivariate models supported the univariate findings and defined complex time-dependent interactions presented graphically. The cerebral and renal circulations may compete for blood flow with critical limitations of cardiac output. The cerebral and renal-somatic beds have different circulatory control mechanisms that can be manipulated to change the distribution of cardiac output by altering the arterial carbon dioxide tension. Monitoring cerebral and renal circulations with near infrared spectroscopy can provide rational physiologic targets for individualized treatment.

Volume blood flow-based indices of fetal brain sparing in the second half of pregnancy: A longitudinal study.

Cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) are clinically used as a measure of fetal brain sparing. These are calculated as the ratios between the pulsatility indices (PIs) of middle cerebral (MCA) and umbilical (UA) arteries, and are an indirect representation of the balance between cerebral and placental perfusion. Volume blood flow (Q)-based ratios, ie Q-CPR or Q-UCR, would directly reflect the distribution of fetal cardiac output to the placenta and brain. Thus, we aimed to determine the development pattern of Q-CPR and Q-UCR during the second half of pregnancy, construct reference intervals, and evaluate their association with CPR and UCR. In a longitudinal cohort study of low-risk pregnancies, the inner diameter of the fetal superior vena cava (SVC) and umbilical vein (UV) was measured and velocity waveforms were obtained from the MCA, UA, UV and SVC using ultrasound at approximately 4-weekly intervals from 20 to 41weeks. The CPR was calculated as PIMCA /PIUA and the inverse ratio was the UCR. Cerebral and placental blood flows were estimated as the product of mean velocity and cross-sectional area of the SVC and UV, respectively. Q-CPR was calculated as QSVC /QUV and the inverse as the Q-UCR. Gestational age-specific reference intervals were calculated and associations between variables were tested using multilevel regression modeling. Longitudinal reference intervals of Q-CPR and Q-UCR were established based on 471 paired measurements of QSVC and QUV obtained serially from 134 singleton pregnancies. The mean Q-CPR increased from 0.4 to 0.8 during the second half of pregnancy and Q-UCR declined from 2.5 to 1.3, while the CPR and UCR had U-shaped curves but in opposite directions. No significant correlation was found between CPR and Q-CPR (R=0.10; P=.051), or UCR and Q-UCR (R=0.09; P=.11), and the agreement between PI-based and Q-based indices of fetal brain sparing was poor. Indices of fetal brain sparing based on placental and cerebral volume blood flow differ from those calculated from UA and MCA PIs. They correlated poorly with conventional CPR and UCR, indicating that they may provide additional/different physiological information. Reference values of Q-CPR and Q-UCR established here can be useful to investigate their clinical value further.

Pharmacokinetic and pharmacodynamic basis for developing modified-release formulations of furosemide

Furosemide has a narrow absorption window restricted to the upper part of the gastrointestinal tract due to its ionization in the gut. Therefore, dissolution of the dose entirely in the stomach was the main aim in the development of gastroretentive extended-release dosage forms in order to sustain its delivery without losing bioavailability. Just as pharmacokinetics (PK) is a prerequisite for observing a pharmacodynamic response (PD) in the individual, the intensity of such a response could also modulate the PK of the drug whenever some physiological mechanism triggered an increase or decrease in the renal fraction of cardiac output. The urine volume increase caused by furosemide triggers the arrival of a supplementary number of molecules at the site of action, and therefore its urinary excretion rate experiences an increase in line with this new cardiac output distribution. It was found that the diuretic effect of furosemide conditioned its urinary excretion clearance. Therefore, its urinary recovery would not reflect the systemic bioavailability of formulations, but both their actual bioavailability at the biophase and their diuretic responses instead. Extended drug input yielded a more efficient diuretic response than the whole dose given rapidly, provided that drug levels at the action site were above the minimum effective concentration. A deep knowledge in the pharmacodynamics-pharmacokinetics (PD-PK) relationships is fundamental to achieve successful furosemide dosage forms. The relation between: drug excretion rates and the intensity of urine output; diuretic efficiency and drug delivery rates; and the benefit of sustained drug delivery are here analyzed. All this together leads us to conclude that the best strategy for developing gastroretentive dosage forms of furosemide would be by including two moieties within the formulation: an accelerated-release loading dose and an extended-release maintenance dose.

États de choc : grands cadres étiologiques, prise en charge initiale

Shock states are the leading causes of intensive care admission and are nowadays associated with high morbidity and mortality. They are driven by a complex physiopathology and most frequently a multifactorial mechanism. They can be separated in whether a decrease of oxygen delivery (quantitative shock) or an abnormal cell distribution of cardiac output (distributive shock). Septic, cardiogenic and hypovolemic shocks represent more than 80% of shock etiologies. Clinical presentation is mostly characterized by frequent arterial hypotension and sign of poor clinical perfusion. Hyperlactatemia occurs in most of shock states. The diagnostic of shock or earlier reversible “pre-shock” states is urgent in order to initiate adequate therapy. Therefore, orientation and therapies must be discussed with intensive care physiologists in a multidisciplinary approach. Etiologic investigation and correction is a primary concern. Hemodynamic and respiratory support reflect another part of initial therapy toward normalization of cell oxygenation. Fluid resuscitation is the corner stone part of initial therapy of any form of shock. Vasoconstrictive drugs or inotropic support still often remain necessary. The primary goal of initial resuscitation should be not only to restore blood arterial pressure but also to improve clinical perfusion markers. On the biological side, decrease of lactate concentration is associated with better outcome.

Design of an In Vitro Mock Circulatory Loop to Reproduce Patient-Specific Vascular Conditions: Toward Precision Medicine

Abstract Patient-specific hemodynamic studies have attracted considerable attention in recent years due to their potential to improve diagnosis and optimize clinical treatment of cardiovascular diseases. Personalized computational models have been extensively investigated as a tool to improve clinical outcomes and are often validated against in vitro experimental data. Replicating patient-specific conditions in vitro is thus becoming increasingly important in cardiovascular research; experimental platforms can not only allow validation of in silico approaches but can also enable physical testing of various intervention scenarios and medical devices. Current experimental approaches suffer from shortcomings regarding personalization and biomimicry. To address some of these limitations, we have designed and developed a novel in vitro platform for the study of complex patient-specific vascular pathologies. This is achieved by using novel tunable three-element Windkessel vasculature simulators and a computer controlled pulsatile pump, coupled with mathematical models and computer routines to calibrate the parameters according to the available clinical datasets. In particular, the vessel inlet flow rate waveform and the afterload resistances and compliances are tuned in order to obtain target systolic and diastolic pressures, and cardiac output (CO) distribution. Pulse frequency (40–70 bpm), CO (2–5 l/min), resistance (0.03–10.6 mmHg s/ml), and compliance (0.07–1 ml/mmHg) values have been tested and the overall reliability of the platform components as well as its computer routines to reproduce controlled physiological conditions demonstrated.

Development of a PBPK Model for Silver Accumulation in Chub Infected with Acanthocephalan Parasites.

Simultaneous presence of metals and parasites in fish might lead to potential risks to human health. Parasites might influence metal accumulation and disturb detoxification in fish, thereby affecting biomarkers of fish responses as well as metal biomagnification in humans. It is, therefore, of importance to take into account parasite infection when investigating metal accumulation in fish. However, mechanisms of metal accumulation and distribution in fish-parasite systems are not integrated into current approaches. The present study proposes a new physiologically based pharmacokinetic model for mechanistic simulation of metal partitioning between intestinal parasites and their hosts. As a particular case, Ag accumulation in the system of chub Squalius cephalus and the acanthocephalan Pomphorhynchus tereticollis was investigated. As a novelty, fish cardiac output and organ-specific blood flow distribution were incorporated in our model. This approach distinguishes the current model from the ones developed previously. It also facilitates model extrapolation and application to varying conditions. In general, the model explained Ag accumulation in the system well, especially in chub gill, storage (including skin, muscle, and carcass), and liver. The highest concentration of Ag was found in the liver. The accumulation of Ag in the storage, liver, and gill compartments followed a similar pattern, i.e., increasing during the exposure and decreasing during the depuration. The model also generated this observed trend. However, the model had a weaker performance for simulating Ag accumulation in the intestine and the kidney. Silver accumulation in these organs was less evident with considerable variations.

Circulatory changes during gestational development of the sheep and human fetus.

Circulatory changes during gestational development of the human fetus have been considered to be similar to those noted in studies of the lamb fetus. Blood flow measurements derived by Doppler ultrasound and magnetic resonance imaging techniques in human fetuses at various stages of gestation have been compared with those in the lamb. Combined ventricular output relative to fetal body weight does not change significantly with growth in the lamb or human. However, the proportion of cardiac output to the brain increases markedly in the human, but only slightly in the lamb fetus in the latter half of gestation. Cardiac output distribution to other organs also changes little in the lamb, but in the human, there is a marked decrease in the proportion distributed to the placenta and an increase in pulmonary flow. The developmental changes in the distribution of combined ventricular output in the human fetus may modify the responses to circulatory disturbances, such as congenital cardiovascular malformations, dependent on gestation.

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS

BackgroundLung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS.MethodsTwelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH2O and limited peak inspiratory pressure (17 ± 4 cmH2O) versus increased peak inspiratory pressure (23 ± 6 cmH2O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t–test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively.ResultsMechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p < 0.001, respectively), increased cardiac output (140 ± 32 vs. 110 ± 22 ml/min/kg, p<0.05) and regional blood flow in the myocardium, brain and spinal cord, adrenal and thyroid glands, the mucosal layers of the esophagus and jejunum, the muscularis layers of the esophagus and duodenum, and the gall and urinary bladders. Perfusion of kidneys, pancreas, spleen, hepatic arterial bed, and the mucosal and muscularis blood flow to the other evaluated intestinal regions remained unchanged.ConclusionsIn this porcine model of ARDS mechanical ventilation with limited peak inspiratory pressure resulting in moderate respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Vascular distensibilities have minor effects on intracardiac shunt patterns in reptiles

The different vascular distensibilities of systemic and pulmonary circuits were recently proposed as an important mechanism defining the direction of cardiac shunt and the distribution of cardiac output in vertebrates with undivided cardiac ventricles. In short, the more distensible pulmonary vascular bed was proposed to accommodate a larger portion of the blood ejected from the heart when cardiac output increases. To evaluate this hypothesis, we performed a meta-analysis based on fourteen previously published studies in two species of reptiles (the freshwater turtle, Trachemys scripta, and the South American rattlesnake, Crotalus durissus) to describe how cardiac shunt patterns change when cardiac output increases. We found no general linear relation between total blood flow and systemic or pulmonary blood flows. Thus, cardiac output alterations cannot be used as a reliable reference for prediction of shunt patterns in both T. scripta and C. durissus. Hence, differential distensibilities appear to be of minor importance for the determination of cardiac shunt patterns in the species analyzed. We speculate that the lack of correlation in these phylogenetically distant species may indicate that this is a common trend within non-crocodilian reptiles.

D2. Screening of preeclampsia (PE) in the first trimester: high total vascular resistance (TVR) with a reduced fat mass increase the risk in normo BMI patients

Introduction: Abnormalities of cardiac output, TVR and water body distribution are connected with PE and foetal growth restriction (FGR).Targets: To identify patients at risk of PE in the first trimester through USCOM system, bioimpedance and combined screening (maternal history, biophysical and biochemical markers). We enrolled 150 healthy nulliparous women with normal BMI.Results: The patients were divided into two groups: Group A (TVR <1200 dynes sec cm−5), Group B (TVR41200 dynes sec cm−5). Lower values of the Cardiac Output (CO), Cardiac index (CI), Inotropy index (INO), Heart rate (HR) and higher values of Flow Time correct (TFC) have been highlighted in the group B (p < 0.01) compared to group A. 8% of study population developed PE or PE + FGR. In this group 75% of the patients presented high TVR values and 50% is at high risk on the basis of combined screening. We found lower Fat Mass in complicated pregnancies with high TVR values compared to uncomplicated pregnancies with high TVR (Table 1).Conclusions: High TVR and lower Fat Mass in the first trimester may be an early marker of PE more than the combined screening. Moreover, lower fat mass increases the positive predictive value of isolated high TVR from 18% to 50% (Figure 1).Figure 1. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) of high Total Vascular Resistence (TVR), Combined first trimester screening (maternal history + mean artery pressure + pulsatility index of uterine artery Doppler + PAPP-A + PlGF) and high TVR + Fat Mass <20%.

Systemic haemodynamics and regional tissue oxygen saturation after bidirectional cavopulmonary shunt: positive pressure ventilation versus spontaneous breathing

Spontaneous breathing has been shown to improve global haemodynamics in patients with bidirectional cavopulmonary shunt. What has not been evaluated, however, is the effect of spontaneous breathing on the distribution of cardiac output after bidirectional cavopulmonary shunt. We investigated the effects of extubation on systemic haemodynamics and regional tissue oxygen saturation, and determined whether redistribution of cardiac output is present after extubation in these patients. In 24 patients undergoing bidirectional cavopulmonary shunt, standard haemodynamic variables including heart rate, arterial blood pressure and central venous pressure were monitored continuously. Near-infrared spectroscopy of the brain and mesenteric circulation was monitored and recorded every hour. Cardiac index, derived from ascending aorta flow, was measured by ultrasound at three time points: 30 min before, 30 min after and 12 h after extubation. The central venous pressure decreased significantly from 19.50 ± 3.65 mmHg before extubation to 16.17 ± 3.41 mmHg 30 min after extubation (P = 0.006) and 13.96 ± 2.49 mmHg 12 h after extubation (P = 0.001). Cardiac index increased significantly from 3.32 ± 0.43 l/min/m(2) before extubation to 3.73 ± 0.51 l/min/m(2) 30 min after extubation (P = 0.012) and 3.98 ± 0.54 l/min/m(2) 12 h after extubation (P = 0.001). Cerebral oxygen saturation increased from 50.83 ± 5.84% before extubation to 56.79 ± 8.64% 30 min after extubation (P = 0.023), then remained unchanged for the following 12 h. Mesenteric oxygen saturation remained unchanged during the early period of extubation, but increased significantly 12 h after extubation (P = 0.002). The lower values of cerebral oxygen saturation before extubation indicated that the cerebral blood flow was less satisfactory. During the early period of extubation, despite the increase in cardiac index, the mesenteric oxygen saturation is lower than that at 12 h after extubation, suggesting that the obligatory increase in respiratory muscle perfusion and the increase in cerebral oxygen saturation have utilized most of the flow from the increased cardiac index. The increase in mesenteric oxygen saturation 12 h after extubation suggests a gradual improvement in microcirculation and macrocirculation.

Ventricular outputs, central blood flow distribution and flow pattern through the aortic isthmus of fetuses with simple transposition of the great arteries.

Our objective was to determine the impact of simple transposition of the great arteries (TGA) on fetal left ventricular (LV) and right ventricular (RV) performances and central circulatory dynamics including the aortic isthmus. Ventricular stroke volumes were calculated as the product of the cross-sectional area of the corresponding semi-lunar valve and the flow velocity integral through these valves. Volume flow in ductus arteriosus (QDA ) was evaluated using the same technique. Flow through the lungs (QLUNGS ) was calculated by subtracting net QDA from flow in main pulmonary artery [net QDA = QDA minus retrograde ductus arteriosus (DA) diastolic flow]. Relative performance of each ventricle expressed as percentage of combined cardiac output was also indirectly assessed by the aortic isthmus systolic index (ISI) (nadir of incisura/peak systolic of the Doppler waveforms in the isthmus); the relation between ISI and QLUNGS was investigated. Fifty-one fetuses with TGA were compared with 74 normal controls matched for gestational age. TGA fetuses had higher QLV at T2 (58.6 ± 9.4% vs. 43.4 ± 5.0%, p < 0.001) and T3 (53.7 ± 8.9% vs. 43.9 ± 5.7%, p < 0.001). QLUNGS was higher in fetuses with TGA, in the second (50.4 ± 16.3% vs. 39.0 ± 16.8%, p = 0.007) and third trimesters of gestation (52.8 ± 22.0% vs. 37.1 ± 16.3%, p = 0.005). No difference was found between ISI values from normal and TGA groups. A significant inverse correlation was observed between ISI and QLUNGS (r = -0.55, p = 0.006). Central distribution of combined cardiac output of fetuses with simple TGA is characterized by a greater QLUNGS leading to a dominant LV. In prenatal TGA, changes in QLUNGS could be monitored by measuring ISI. The clinical importance of this last observation deserves further investigations.

Heat stress redistributes blood flow in arteries of the brain during dynamic exercise.

We hypothesized that heat stress would decrease anterior and posterior cerebral blood flow (CBF) during exercise, and the reduction in anterior CBF would be partly associated with large increase in extracranial blood flow (BF). Nine subjects performed 40 min of semirecumbent cycling at 60% of the peak oxygen uptake in hot (35°C; Heat) and thermoneutral environments (25°C; Control). We evaluated BF and conductance (COND) in the external carotid artery (ECA), internal carotid artery (ICA), and vertebral artery (VA) using ultrasonography. During the Heat condition, ICA and VA BF were significantly increased 10 min after the start of exercise (P < 0.05) and thereafter gradually decreased. ICA COND was significantly decreased (P < 0.05), whereas VA COND remained unchanged throughout Heat. Compared with the Control, either BF or COND of ICA and VA at the end of Heat tended to be lower, but not significantly. In contrast, ECA BF and COND at the end of Heat were both higher than levels in the Control condition (P < 0.01). During Heat, a reduction in ICA BF appears to be associated with a decline in end-tidal CO2 tension (r = 0.84), whereas VA BF appears to be affected by a change in cardiac output (r = 0.87). In addition, a change in ECA BF during Heat was negatively correlated with a change in ICA BF (r = -0.75). Heat stress resulted in modification of the vascular response of head and brain arteries to exercise, which resulted in an alteration in the distribution of cardiac output. Moreover, a hyperthermia-induced increase in extracranial BF might compromise anterior CBF during exercise with heat stress.

Distribution of cardiac output to the brain across the adult lifespan

A widely accepted dogma is that about 15–20% of cardiac output is received by the brain in healthy adults under resting conditions. However, it is unclear if the distribution of cardiac output directed to the brain alters across the adult lifespan and is modulated by sex or other hemodynamic variables. We measured cerebral blood flow/cardiac output ratio index in 139 subjects (88 women, age 21–80 years) using phase-contrast magnetic resonance imaging and echocardiography. Body mass index, cardiac systolic function (eject fraction), central arterial stiffness (carotid-femoral pulse wave velocity), arterial pressure, heart rate, physical fitness (VO2 max), and total brain volume were measured to assess their effects on the cardiac output–cerebral blood flow relationship. Cerebral blood flow/cardiac output ratio index decreased by 1.3% per decade associated with decreases in cerebral blood flow (P < 0.001), while cardiac output remained unchanged. Women had higher cerebral blood flow, lower cardiac output, and thus higher cerebral blood flow/cardiac output ratio index than men across the adult lifespan. Age, body mass index, carotid-femoral pulse wave velocity, and arterial pressure all had negative correlations with cerebral blood flow and cerebral blood flow/cardiac output ratio index (P < 0.05). Multivariable analysis adjusted for sex, age showed that only body mass index was negatively associated with cerebral blood flow/cardiac output ratio index (β = −0.33, P < 0.001). These findings demonstrated that cardiac output distributed to the brain has sex differences and decreases across the adult lifespan and is inversely associated with body mass index.

Is nitric oxide mediated sympatholysis improved with exercise? Yes or nNO?

Exercise causes marked elevations in sympathetic activity to skeletal muscle beds, the magnitude of which is largely dependent on exercise mode, intensity and the amount of active muscle mass. This sympathetic outflow results in vasoconstriction within inactive muscle beds, whilst in active muscle beds exercise induces the release of sympatholytic factors (i.e. ATP, prostaglandins (PGs), and nitric oxide (NO)). These factors act to attenuate or abolish sympathetic vasoconstriction during exercise. Functional sympatholysis reflects this ability of active muscle beds to release sympatholytic factors to locally attenuate the sympathetic vasoconstrictor response associated with exercise. Combined constrictive and sympatholytic processes allow for cardiac output redistribution, which facilitates adequate perfusion and O2 delivery to metabolically active muscle, and ultimately homeostasis. If a large amount of muscle mass were active (e.g. during whole body exercise), a mismatch between these two processes would lead to either under-perfusion (greater vasoconstriction) or hypotension (greater sympatholysis). While the relevance of functional sympatholysis in clinical/disease populations is unclear, numerous pathophysiological conditions are characterized by elevated sympathetic outflow and impaired sympatholysis contributes to elevated vascular resistance and malperfusion of skeletal muscle during exercise (Saltin & Mortensen, 2012). For example, leg vascular conductance appears to be lower during exercise in hypertensive compared to normotensive adults (Mortensen et al. 2014). Moreover, impaired sympatholysis has been linked to reduced muscle perfusion in elderly versus young individuals during exercise (reviewed in Saltin & Mortensen, 2012). Overall, a complex interplay between blood pressure-regulating reflexes (i.e. baroreflex, muscle metaboreflex, central command, etc.), their consequent sympathetic outflow, and the production of local sympat-holytic factors determine cardiac output distribution to contracting skeletal muscle. However, the integration of these processes is poorly understood.

Fetal Ventricular Interactions and Wall Mechanics During Ductus Arteriosus Occlusion in a Sheep Model

We investigated the effect of fetal sheep ductus arteriosus occlusion (DO) on the distribution of cardiac output and left and right ventricular function by tissue and pulsed Doppler at baseline; after 15 and 60 min of DO induced with a vascular occluder; and 15 min after release of DO. Ductal occlusion decreased fetal pO2. Mean left ventricular output increased (p < 0.001) from 725 to 1013 mL/min, and right ventricular (1185 mL/min vs. 552 mL/min) and systemic (1757 mL/min vs. 1013 mL/min) cardiac outputs fell (p < 0.001) after 15 min of DO, compared with baseline. Pulmonary vascular impedance decreased and volume blood flow increased more than threefold during DO, whereas foramen ovale volume blood flow remained unchanged. Left ventricular systolic function was unaffected, whereas isovolumic relaxation velocity deceleration decreased. Right ventricular functional indices remained unchanged. We conclude that DO increased pulmonary volume blood flow, not foramen ovale volume blood flow. Left ventricular output increased, although not as much as right ventricular output fell, resulting in decreased systemic cardiac output. During DO, left ventricular function exhibited diminished relaxation.

Cerebral oxygenation and hyperthermia

Hyperthermia is associated with marked reductions in cerebral blood flow (CBF). Increased distribution of cardiac output to the periphery, increases in alveolar ventilation and resultant hypocapnia each contribute to the fall in CBF during passive hyperthermia; however, their relative contribution remains a point of contention, and probably depends on the experimental condition (e.g., posture and degree of hyperthermia). The hyperthermia-induced hyperventilatory response reduces arterial CO2 pressure (PaCO2) causing cerebral vasoconstriction and subsequent reductions in flow. During supine passive hyperthermia, the majority of recent data indicate that reductions in PaCO2 may be the primary, if not sole, culprit for reduced CBF. On the other hand, during more dynamic conditions (e.g., hemorrhage or orthostatic challenges), an inability to appropriately decrease peripheral vascular conductance presents a condition whereby adequate cerebral perfusion pressure may be compromised secondary to reductions in systemic blood pressure. Although studies have reported maintenance of pre-frontal cortex oxygenation (assessed by near-infrared spectroscopy) during exercise and severe heat stress, the influence of cutaneous blood flow is known to contaminate this measure. This review discusses the governing mechanisms associated with changes in CBF and oxygenation during moderate to severe (i.e., 1.0°C to 2.0°C increase in body core temperature) levels of hyperthermia. Future research directions are provided.