Experimental physiology
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Experimental physiology · Oct 2021
Effect of different levels of stroke volume variation on the endothelial glycocalyx of patients undergoing colorectal surgery: A randomized clinical trial.
What is the central question of this study? Massive infusion can destroy the endothelial glycocalyx. We compared the serum concentrations of endothelial glycocalyx components and atrial natriuretic peptide and the outcomes of patients with different levels of stroke volume variation (SVV). What is the main finding and its importance? With a decrease in SVV, the serum concentrations of endothelial glycocalyx components and atrial natriuretic peptide increased, whereas the oxygenation index decreased. When the intraoperative SVV was maintained at 7-10%, the patients had better postoperative recovery and shorter postoperative hospital stays. Therefore, it is advisable to maintain the SVV between 7 and 10%. ⋯ Dynamic haemodynamic parameters, such as stroke volume variation (SVV), can be used for blood volume monitoring. However, studies have determined the SVV threshold but not the optimal level. The endothelial glycocalyx (EG) plays an important role in maintaining vascular permeability. Moreover, rapid and massive infusion can lead to the degradation, shedding and destruction of the EG. We aimed to explore the effects of different SVV values (11-14, 7-10 or 3-6%) on the EG in 54 patients who were scheduled for elective colorectal tumour surgery and to identify the optimal peri-operative fluid therapy strategy. The concentrations of EG degradation products (heparin sulphate, hyaluronic acid and syndecan-1) and atrial natriuretic peptide were higher when the SVV was maintained between 3 and 6% after fluid therapy compared with pre-infusion (P < 0.05). Comparison of postoperative complications and hospitalization time among the three SVV levels was not statistically significant (P > 0.05). The postoperative hospitalization time in patients with SVV of 7-10% was shorter than that in patients with SVV of 3-6%. Infusion of a large volume of fluid, with increasing EG degeneration and atrial natriuretic peptide concentrations, might be related to postoperative outcomes.
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Experimental physiology · Sep 2020
The impact of damage-associated molecular patterns on the neurotransmitter release and gene expression in the ex vivo rat carotid body.
What is the central question of this study? Are carotid bodies (CBs) modulated by the damage-associated molecular patterns (DAMPs) and humoral factors of aseptic tissue injury? What are the main findings and their importance? DAMPs (HMGB1, S100 A8/A9) and blood plasma from rats subjected to tibia surgery, a model of aseptic injury, stimulate the release of neurotransmitters (ATP, dopamine) and TNF-α from ex vivo rat CBs. All-thiol HMGB1 mediates upregulation of immune-related biological pathways. These data suggest regulation of CB function by endogenous mediators of innate immunity. ⋯ The glomus cells of carotid bodies (CBs) are the primary sensors of arterial partial O2 and CO2 tensions and moreover serve as multimodal receptors responding also to other stimuli, such as pathogen-associated molecular patterns (PAMPs) produced by acute infection. Modulation of CB function by excessive amounts of these immunomodulators is suggested to be associated with a detrimental hyperinflammatory state. We have hypothesized that yet another class of immunomodulators, endogenous danger-associated molecular patterns (DAMPs), released upon aseptic tissue injury and recognized by the same pathogen recognition receptors as PAMPs, might modulate the CB activity in a fashion similar to PAMPs. We have tested this hypothesis by exposing rat CBs to various DAMPs, such as HMGB1 (all-thiol and disulfide forms) and S100 A8/A9 in a series of ex vivo experiments that demonstrated the release of dopamine and ATP, neurotransmitters known to mediate CB homeostatic responses. We observed a similar response after incubating CBs with conditioned blood plasma obtained from the rats subjected to tibia surgery, a model of aseptic injury. In addition, we have investigated global gene expression in the rat CB using an RNA sequencing approach. Differential gene expression analysis showed all-thiol HMGB1-driven upregulation of a number of prominent pro-inflammatory markers including Il1α and Il1β. Interestingly, conditioned plasma had a more profound effect on the CB transcriptome resulting in inhibition rather than activation of the immune-related pathways. These data are the first to suggest potential modulation of CB function by endogenous mediators of innate immunity.
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What is the central question of this study? Are the mechanisms that cause ventricular interdependence different when due to primary right to left ventricular pressure loading? What is the main finding and its importance? An instantaneous selective increase in aortic pressure causes an immediate increase in right ventricular end-systolic pressure independent of the pericardium, whereas a selective increase in pulmonary artery pressure decreases left ventricular diastolic compliance owing to a subsequent increasing right ventricular end-diastolic volume as a function of an intact pericardium limiting biventricular volume. Changes in contraction synchrony of either ventricle do not appear to be causing these effects. ⋯ I characterized the dynamic factors determining ventricular interdependence with and without the pericardium. I measured right (RV) and left ventricular (LV) pressures and volumes simultaneously using conductance catheters in seven pentobarbitone-anaesthetized open-chested 5- to 7-week-old piglets. I studied these effects during apnoea, inferior vena caval occlusion and rapid partial aortic and pulmonary arterial occlusions. Conductance catheter-defined long-axis regional volumes were assessed to define regional contractile synchrony. Closed-pericardium measures were made from an initial (baseline) volume, then after two 20 ml kg-1 fluid loads followed by an open-pericardium step. Baseline RV and LV volumes were similar. Aortic occlusion increased LV pressures and volumes and RV end-systolic pressure such that RV end-systolic elastance increased without changes in RV contraction synchrony, not affected by the pericardium. Pulmonary artery occlusion increased RV end-systolic pressure but not end-systolic volume. On the subsequent beat, RV end-diastolic pressure increased, whereas LV end-diastolic volume and diastolic compliance decreased. These effects were attenuated by opening the pericardium. Contraction synchrony across longitudinal segments was unaltered by either aortic or pulmonary artery occlusion. I conclude that the determinants of systolic and diastolic ventricular interdependence are different. Increasing RV pressures causes diastolic RV-to-LV interdependence, decreasing LV diastolic compliance and dependent on an intact pericardium. An increase in LV end-systolic pressure increases RV end-systolic elastance independent of the pericardium and has a minimal effect on RV diastolic function or contraction synchrony.
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Experimental physiology · May 2020
Cerebrovascular reactivity to carbon dioxide is not influenced by variability in the ventilatory sensitivity to carbon dioxide.
What is the central question of this study? Do differing magnitudes of ventilation influence cerebrovascular CO2 reactivity and the cerebral blood flow response to increases in arterial carbon dioxide? What is the main finding and its importance? While a greater ventilation, through voluntary hyperventilation, is associated with a higher anterior cerebral blood flow during carbon dioxide breathing, this elevated cerebral blood flow is due to a higher blood pressure and not ventilation per se. A greater ventilation, through voluntary hyperventilation, does not influence global or posterior cerebral blood flow during carbon dioxide breathing. Cerebrovascular reactivity to carbon dioxide is not influenced by an individual's ventilatory sensitivity to carbon dioxide. ⋯ Recent work demonstrated an influence of ventilation on cerebrovascular reactivity to CO2 ; however, the concomitant influence of changes in mean arterial blood pressure (MAP) on ventilation-induced differences in cerebral blood flow (CBF) has yet to be examined in this context. Healthy participants (n = 15; 25 ± 3 years of age; 179 ± 6 cm height; 74 ± 10 kg weight; 3 female) underwent end-tidal forcing to increase their partial pressure of end-tidal CO2 by +3, +6 and +9 mmHg above baseline in 5-min sequential steps while maintaining iso-oxia. This protocol was then repeated twice, with participants hyperventilating and hypoventilating by ∼30% compared to the first trial. Intra-cranial and extra-cranial CBF were measured using ultrasound. The MAP (finger photo-plethysmography) was higher during the hyperventilation and hypoventilation trials compared to normal ventilation (main effects, P < 0.05 for both). While internal carotid artery blood flow was higher during the hyperventilation trial compared to normal ventilation (P = 0.01), this was due to a higher MAP, as indicated by analysis of conductance values (P = 0.68) or inclusion of MAP in covariate analysis (P = 0.11). Global CBF (P = 0.11) and vertebral artery blood flow (P = 0.93) were unaffected by the magnitude of ventilation. Further, CO2 reactivity was not affected by the different breathing trials (P > 0.05 for all). Retrospective analysis of a larger data set (n = 53) confirmed these observations and demonstrated no relationships between the ventilatory and global CBF response to hypercapnia (r2 = 0.04; P = 0.14). Therefore, when differences in MAP are accounted for, cerebrovascular CO2 reactivity (assessed via end-tidal forcing) is independent of the magnitude of ventilation.
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What is the central question of this study? Are sex difference in the central airways present in healthy paediatric patients? What is the main finding and its importance? In patients ≤12 years we found no sex differences in central airway luminal area. After 14 years, the males had significantly larger central airway luminal areas than the females. The sex differences were minimized, but preserved when correcting for height. Luminal area is the main determinant of airway resistance and our finding could help explain sex differences in pulmonary system limitations to exercise in paediatric patients. ⋯ Cross-sectional airway area is the main determinant of resistance to airflow in the respiratory system. In paediatric patients (<18 years), previous evidence for sex differences in cross-sectional airway area was limited to patients with history of pulmonary disease or cadaveric studies with small numbers of subjects. These studies either only report tracheal data and do not include a range of ages or correct for height. Therefore, we sought to assess sex differences in airway luminal area utilizing paediatric patients of varying ages and no history of respiratory disease. Using three-dimensional reconstructions from high-resolution computed tomography scans, we retrospectively assessed the cross-sectional airway area in healthy paediatric females (n = 97) and males (n = 128) over a range of ages (1-17 years). The areas of the trachea, left main bronchus, left upper lobe, left lower lobe, right main bronchus, intermediate bronchus and right upper lobe were measured at three discrete points by a blinded investigator. No differences between the sexes were noted in the cross-sectional areas of the youngest (ages 1-12 years) patients (P > 0.05). However, in patients ≥14 years the cross-sectional areas were larger in the males compared to females in most airway sites. For instance, the cross-sectional size of the trachea was 25% (218 ± 44 vs. 163 ± 24 mm2 , P < 0.01) larger in males vs. females among ages 13-17 years. When accounting for height, these sex differences in airway areas were attenuated, but persisted. Our results indicate that sex differences in paediatric airway cross-sectional area manifest after age ≥14 years and are independent of height.