Changes In Systemic Blood Flow Research Articles

Leveraging doppler ultrasound imaging to measure pulse wave velocity changes in a mouse model of arterial stiffening to elucidate molecular pathways underlying cerebral damage

AbstractBackgroundThe highly vascularized brain is particularly vulnerable to changes in pulsatility of blood flow. With age, elastin in arteries breaks down and is replaced by collagen, making arteries less compliant and resulting in arterial stiffening. Stiffening alters pulsatility, which can be measured by pulse wave velocity (PWV), and damages small capillary beds and the neurovascular unit (NVU). The NVU is essential for proper delivery of oxygen and nutrients to the brain. Human studies have demonstrated associations between increased arterial stiffness and biomarkers of Alzheimer’s disease (AD) and neurodegeneration. We adapted a doppler ultrasound imaging method previously only used in rats to measure PWV in a mouse model of arterial stiffening to advance our understanding of the molecular underpinnings of AD and neurodegeneration.Method7‐month‐old, C57BL/6, male and female mice underwent a carotid calcification surgery, where the carotid artery was exposed to 0.3 mol/L CaCl2 (or saline as a control) for 20 minutes. PWV was measured using doppler ultrasound imaging before and after surgery. Two weeks post‐surgery, mice underwent behavioral testing, including locomotor activity, elevated zero maze, Barnes maze, and nest building. Collagen, calcium, and elastin levels in the carotid artery were determined 4 weeks post‐surgery by immunohistochemistry.ResultPreliminary results demonstrate the carotid calcification surgery successfully increased PWV in mice three weeks post‐surgery. Surgery did not inhibit behavioral task performances two weeks post‐operative. Additional data collection is underway applying this method in two transgenic AD mouse models, APP/PSEN1 and P301S, which will include behavioral testing and histological assessment of NVU components, specifically endothelial cells (CD31/PECAM), pericytes (PDGRFb), and astrocytes (GFAP) in the hippocampus.ConclusionElucidating a clear molecular link between increased arterial stiffness and cognition is essential to understanding how age‐related changes in systemic blood flow may influence AD pathology and neurodegeneration. Our preliminary results demonstrate that doppler ultrasound imaging, previously only used in rats, can be applied in mice as a reliable measurement of PWV. We will leverage this model to test the hypothesis that increased PWV is associated with worse spatial learning and memory, impaired functioning of the NVU, and increased AD pathology.

The Effects of Targeted Changes in Systemic Blood Flow and Mean Arterial Pressure on Urine Oximetry During Cardiopulmonary Bypass

Poor medullary oxygenation is implicated in the evolution of acute kidney injury. The authors sought to determine if increasing systemic flow and mean arterial pressure could improve urine oxygen tension (PuO2) measured in the bladder, a surrogate of kidney medullary oxygenation, in patients undergoing on-pump cardiac surgery. Randomized crossover study. University-affiliated hospital. Twenty adult patients undergoing cardiopulmonary bypass (CPB) with expected cross-clamp time of >60 minutes and estimated glomerular filtration rate of >30 mL/min/1.73m2. Sequential 20-minute periods of 2 interventions: Intervention H ("High") or Intervention N ("Normal"). The order of interventions was determined by randomization. Intervention H: targeted CPB flow 3.0 L/min/m2 and mean arterial pressure (MAP) 80 mmHg. Intervention N: targeted CPB flow 2.4 L/min/m2 and MAP 65 mmHg. PuO2 was measured by an oxygen sensor introduced into the bladder via a urinary catheter. Clear separation was achieved in CPB flow and MAP between intervention periods (p < 0.001 for group-time interaction). PuO2 during Intervention H was higher than during Intervention N (p < 0.001 for group-time interaction). After 17 minutes, PuO2 was statistically higher in Intervention H at each time point. There were no differences in markers of hemolysis between interventions. PuO2 was higher when systemic flow and MAP were increased during CPB. These findings suggest that PuO2 is responsive to changes in hemodynamics and that higher flow and pressure may improve medullary oxygenation.

Efeito do exercício físico sobre os parâmetros hemodinâmicos

To assess the effects of aerobic physical exercise on the Doppler velocimetry of fetal vessels in pregnant women with no clinical or obstetrical complications. A cross-sectional study was conducted on 10 healthy low-risk pregnant women at 2 different gestational times: between the 26th and 29th week and 6 days, and at the end of pregnancy, between the 30th and 35th week. The patients were submitted to aerobic physical exercise on a treadmill until reaching fatigue. Ultrasonographic data were obtained at rest and after physical exercise (Doppler velocimetry indices for the umbilical artery, middle cerebral artery, ductus venosus, and uterine arteries). Data were analyzed statistically by the paired and independent Student's t-test using the Statistical Package for the Social Sciences (SPSS) package, version 21.0. A change in the pulsatility index was observed, with an indication of vasodilatation, with a median value of 1.1±0.1 before exercise and of 1.0±0.1 after exercise; the median value of the resistance index was 0.7±0.04 before exercise and 0.6±0.07 after exercise. The median systole/diastole ratio of the umbilical artery was 3.1±0.4 before exercise and 2.9±0.2 (p=0.03) after exercise at the beginning of pregnancy. No changes in the Doppler velocimetry parameters were observed for the uterine arteries, the middle cerebral artery or the ductus venosus after physical activity at either testing time. Paired analysis of pre- and post-activity data showed a reduction of resistance from the first to the second period (p<0.04). Physical exercise does not lead to changes in systemic blood flow or fetal-placental flow in healthy pregnant women, confirming that exercises of mild to moderate intensity can be prescribed.

Translational paradigms in scientific and clinical imaging of cardiac development

Congenital heart defects (CHD) are the most prevalent congenital disease, with 45% of deaths resulting from a congenital defect due to a cardiac malformation. Clinically significant CHD permit survival upon birth, but may become immediately life threatening. Advances in surgical intervention have significantly reduced perinatal mortality, but the outcome for many malformations is bleak. Furthermore, patients living while tolerating a CHD often acquire additional complications due to the long-term systemic blood flow changes caused by even subtle anatomical abnormalities. Accurate diagnosis of defects during fetal development is critical for interventional planning and improving patient outcomes. Advances in quantitative, multidimensional imaging are necessary to uncover the basic scientific and clinically relevant morphogenetic changes and associated hemodynamic consequences influencing normal and abnormal heart development. Ultrasound is the most widely used clinical imaging technology for assessing fetal cardiac development. Ultrasound-based fetal assessment modalities include motion mode (M-mode), two dimensional (2D), and 3D/4D imaging. These datasets can be combined with computational fluid dynamics analysis to yield quantitative, volumetric, and physiological data. Additional imaging modalities, however, are available to study basic mechanisms of cardiogenesis, including optical coherence tomography, microcomputed tomography, and magnetic resonance imaging. Each imaging technology has its advantages and disadvantages regarding resolution, depth of penetration, soft tissue contrast considerations, and cost. In this review, we analyze the current clinical and scientific imaging technologies, research studies utilizing them, and appropriate animal models reflecting clinically relevant cardiogenesis and cardiac malformations. We conclude with discussing the translational impact and future opportunities for cardiovascular development imaging research.

Changes in hemodynamics after rescue surfactant administration

To evaluate the hemodynamic changes occurring after rescue surfactant dosing in relation to the clinical respiratory response in preterm infants with respiratory distress syndrome. We studied 20 infants who received surfactant (poractant alfa) after failing continuous positive airway pressure (CPAP) beyond 2 h of life. Consecutive echocardiograms were performed before the surfactant dose, 10 min after and 1 h after the surfactant dose. Superior vena cava flow, right ventricular output, atrial and patent ductus arteriosus diameter and direction of shunting were measured. A surfactant responder (SR) was defined as an infant whose inspired fraction of oxygen was reduced to air (0.21) by 3 h after surfactant administration. A surfactant non-responder (SNR) was defined as an infant who remained on more than 0.21 at 3 h postsurfactant administration. Concurrent physiological parameters (heart rate, transcutaneous CO2, mean arterial blood pressure, mean airway pressure) were also recorded. Subject characteristics were compared relative to noted hemodynamic effects. Of the 20 infants enrolled in the study, 12 were SR. These infants received surfactant earlier and had increased measures of systemic blood flow after receipt of surfactant compared with baseline. SNR did not have changes in systemic blood flow from baseline after surfactant dosing. There was no change in ductal shunting or atrial shunting between the two groups. A good clinical response to rescue surfactant is seen in infants who received surfactant earlier and is associated with increase in systemic blood flow. Timing of rescue surfactant administration needs to be further evaluated in larger prospective studies.

Cardiorespiratory effects of changes in end expiratory pressure in ventilated newborns

Background:Positive pressure ventilation in premature infants can improve oxygenation but may diminish cerebral blood flow and cardiac output. Low superior vena cava (SVC) flow increases risk of intraventricular haemorrhage, and...

Abnormal gastric tonometric variables and vasoconstrictor use after left ventricular assist device insertion

Background Abnormal gastric tonometric variables, a surrogate for splanchnic ischemia, occur in approximately 50% of patients at the end of routine cardiac operations and are associated with postoperative morbidity. We sought to determine whether gastric tonometric variables deteriorate after left ventricular assist device insertion and to explore the association between abnormal gastric tonometric variables and vasoconstrictor use. Methods Nineteen patients who had insertion of a left ventricular assist device were enrolled in a prospective, observational study. Automated air tonometry was used to determine the difference between gastric and arterial partial pressure of carbon dioxide (CO 2 gap) at five time points perioperatively. Results Compared with baseline, systemic blood flow was significantly increased at the end of operation (1.9 ± 0.6 versus 2.9 ± 0.7 L · min −1 · m −2, p < 0.0001). Tonometric variables, which were normal at baseline, became abnormal in 90% of patients (baseline CO 2 gap 4 ± 2 mm Hg versus end of operation CO 2 gap 24 ± 15 mm Hg, p < 0.0001). Elevated CO 2 gaps correlated with larger doses of norepinephrine ( r = 0.69, p = 0.001) and vasopressin ( r = 0.88, p < 0.0001). Abnormal gastric tonometric variables at the end of operation correlated with postoperative intensive care unit length of stay ( r = 0.70, p = 0.0009) and multiple organ dysfunction score ( r = 0.64, p = 0.0033). Conclusions Despite a significant increase in systemic blood flow after left ventricular assist device implantation, abnormal gastric tonometric variables developed and were associated with larger vasoconstrictor dose. These data provide evidence that gastric ischemia can develop independently of changes in systemic blood flow and support the potential role of vasoconstrictors as a cause of splanchnic ischemia.

Intestinal tissue oxygenation and tumor necrosis factor-alpha release during systemic blood flow changes in pigs with left ventricular assist devices.

We previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) increased following a reduction in systemic blood flow to 60% or less of the original cardiac output using a left ventricular assist device (LVAD). The aim of this study was to investigate the effect of reducing systemic blood flow on tissue oxygenation in the gastrointestinal tract (GIT) and the consequences of this on TNF-alpha release. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF-alpha of the superior mesenteric vein was measured at baseline and during systemic blood flow changes. Simultaneously, pH, lactate, oxygen delivery index (DO(2)I), oxygen consumption index (VO(2)I), and oxygen extraction (O(2)ER) in the GIT were measured. The pH decreased and the lactate level increased significantly (p < 0.05) at a systemic blood flow of 50% or less. The VO(2)I was positively correlated with DO(2)I. The O(2)ER increased significantly (p < 0.05) with reductions in systemic blood flow to 30% or less. There was a significant (p < 0.01) correlation between TNF-alpha and O(2)ER at levels higher than 55%. These data demonstrate that the GIT oxygenation is inadequate with a reduction in systemic blood flow to 50% and that GIT oxygenation becomes critical at a reduction of 30%. During LVAD weaning, careful attention must be given to the GIT. The pH and lactate may be good markers of the adequacy of tissue oxygenation in the GIT.

Do beta-adrenergic drugs increase microcirculatory blood flow in the gut in sepsis?

Splanchnic blood flow is impaired in sepsis [1]. Therefore, beta-adrenergic agents are frequently administered in sepsis to increase global oxygen delivery in an attempt to increase splanchnic blood flow as well. However, changes in microcirculation can not be predicted by changes in systemic blood flow [2] and the effects of beta-adrenergic drugs on the splanchnic and gut mucosal circulation in sepsis is still not well understood. The aim of this study was to measure the effects of dopexamine and dobutamine, on systemic flow, regional flow and microcirculatory blood flow in the intestinal mucosa in septic shock.

Circadian rhythms in renal function in hypertensive TGR(mRen-2)27 rats and their normotensive controls.

Patients with secondary hypertension frequently display abnormal circadian blood pressure profiles, characterized by a failure to decrease blood pressure at night. The transgenic TGR(mRen-2)27 rat strain, developing fulminant hypertension after the mouse salivary Ren-2 renin gene has been integrated into its genome, provides a fundamental model of genetic hypertension. Because of an inverse circadian blood pressure profile and an unchanged rhythmic pattern of heart rate compared with the normotensive Sprague-Dawley (SPR) strain, it was proposed to serve as an animal model of genetic hypertension. It was the aim of the present study to investigate the circadian rhythmicity in renal function of the transgenic rat to determine whether hypertension and disturbed circadian blood pressure profile would affect kidney function. Urinary water, electrolyte, and protein excretion, as well as glomerular filtration rate and renal plasma flow, were determined in unrestrained freely moving transgenic hypertensive (TGR) and SPR normotensive control rats by collecting urine and arterial blood every 4 h. Significant and similar circadian rhythms were found in renal excretion and hemodynamics in both normotensive and hypertensive strains. Peaks occurred in the active dark period, whereas troughs were found in daytime for all parameters. However, it has to be pointed out that, although the circadian profiles were not grossly perturbed in hypertensive animals, some small differences between SPR and TGR strains did exist in renal function. These discrepancies were precisely related to acrophase, showing a slight phase delay, and also to relative amplitude in TGR. This study demonstrates that the inverted circadian blood pressure profile affected only slightly the circadian rhythms in kidney function in TGR compared with SPR. These findings support the notion that time-dependent changes in systemic blood flow may be of greater importance for circadian regulation of kidney function than systemic blood pressure.