Diurnal Variations in Vascular Endothelial Vasodilation Are Influenced by Chronotype in Healthy Humans

Introduction: The time of day when cardiovascular events are most likely to occur is thought to be aligned with the circadian rhythm of physiological variables. Chronotype has been shown to influence the time of day when cardiovascular events happen, with early chronotypes reported to be more susceptible in the morning and late chronotypes in the evening. However, no studies have investigated the influence of chronotype on physiological variables responsible for cardiovascular regulation in healthy individuals. Methods: 312 individuals completed the Munich ChronoType Questionnaire to assess chronotype. Twenty participants were randomly selected to continue into the main study. In a repeated-measures experiment, participants were tested between 08:00 and 10:00 h and again between 18:00 and 20:00 h. Measurements of mean arterial pressure, heart rate and vascular endothelial vasodilation via flow-mediated dilatation (FMD) were obtained at each session. Results: Individual diurnal differences in mean arterial pressure and heart rate show no significant relationship with chronotype. Diurnal differences in FMD showed a significant correlation (p = 0.010), driven by a clear significant relationship in the evening and not the morning (p < 0.001). Conclusion: These preliminary data indicate that chronotype influences the diurnal variation of endothelial vasodilation measured using flow-mediated dilatation. Furthermore, we show that the influence of chronotype is much stronger in the evening, highlighting an increased susceptibility for later types. These findings are consistent with the diurnal rhythm in cardiovascular events and uncover potential mechanisms of local mediators that may underpin the influence of chronotype in the onset of these events

Hypoxia, not pulmonary vascular pressure induces blood flow through intrapulmonary arteriovenous anastomoses

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times-a-day for 48 h) to prevent increases in PASP, and (3) isocapnic hypoxia with AZ and 8.4% NaHCO3 infusion (AZ+HCO3-) to control for AZ-induced acidosis. Isocapnic hypoxia (20 min) was maintained by end-tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic-hypoxia condition to determine pH, [HCO3-], and PaCO2. AZ decreased pH (-0.08 ± 0.01), [HCO3-] (-7.1 ± 0.7 mmol/l), and PaCO2 (-4.5 ± 1.4 mmHg; p<0.01), while intravenous NaHCO3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (p<0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (p<0.001) following AZ administration while intravenous NaHCO3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (p<0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H+ concentration or PaCO2. Abbreviations list: AZ, acetazolamide; FEV1, forced expiratory volume in 1 second; FIO2, fraction of inspired oxygen; FVC, forced vital capacity; Hb, total haemoglobin; HPV, hypoxic pulmonary vasoconstriction; HR, heart rate; IPAVA, intrapulmonary arteriovenous anastomoses; MAP, mean arterial pressure; PASP, pulmonary artery systolic pressure; PETCO2, end-tidal partial pressure of carbon dioxide; PETO2, end-tidal partial pressure of oxygen; PFO, patent foramen ovale; PVR, pulmonary vascular resistance; Q̇c, cardiac output; RVOT, right ventricular outflow tract; SpO2, oxyhaemoglobin saturation; SV, stroke volume; TRV, tricuspid regurgitant velocity; V̇E, minute ventilation; VTI, velocity-time integra

Laser phase microscopy and functional imaging of living human cancer cells during the cell cycle

The purpose of the investigation was to elaborate a new method of functional imaging of living tumor cells. Human colon carcinoma cells HCT116 were investigated with a conventional light microscope, confocal laser scanning microscope and with a laser phase microscope (LPM). The LPM is a functional imaging technique providing information about cell morphology which is imposed by the physiological inhomogeneity of the refractive index. The phase of the light wave passing through an object contains quantitative information about the object thickness, the shape, and the spatial distribution of the refractive index varying with morphology and chemical composition inhomogeneity inside the object. The new method of investigation of the cells in different stages of the cell cycle is developed. Every phase image of the investigated cells has been compared with conventional light microscopic and confocal microscopic images of the same cell. the relation between the cell state, their morphological peculiarities and the phase characteristics of the measured cell is determined. Data thus acquired, quantitatively characterizing intra- and intercellular processes during the cell cycle, and the method of measurements can be used to investigate with high optic resolution the mechanisms of different physical, chemical and biomolecular interactions with the tumor cells

Advances in the available non-biological pharmacotherapy prevention and treatment of acute mountain sickness and high altitude cerebral and pulmonary oedema

Introduction: The physiological responses on exposure to high altitude are relatively well known, but new discoveries are still being made, and novel prevention and treatment strategies may arise. Basic information has changed little since our previous review in this journal 10 years ago, but considerable more detail on standard therapies, and promising new approaches are now available. Areas covered: Herein, the authors review the role of pharmacological agents in preventing and treating high-altitude illnesses. The authors have drawn on their own experience and that of international experts in this field. The literature search was concluded in March 2018. Expert opinion: Slow ascent remains the primary prevention strategy, with rapid descent for the management of serious altitude illnesses. Pharmacological agents are particularly helpful when rapid ascent cannot be avoided or when rapid descent is not possible. Acetazolamide remains the drug of choice for prophylaxis of acute mountain sickness. However, evidence indicates that reduced dosage schemes compared to the current recommendations are warranted. Calcium channel blockers and phosphodiesterase inhibitors remain the drugs of choice for the management of high-altitude pulmonary edema. Dexamethasone should be reserved for the treatment of more severe cases of altitude illnesses such as cerebral edema.</p

Multiphoton excitation and photodynamic activity of macromolecular derivatizated mTHPC

Multiphoton excitation of photosensitizers in photodynamic therapy constitutes a promising approach, because of the increasing tissue penetration for longer wavelength of illumination. In this contribution the photodynamic activity of polyethylene glycol macromolecular derivatized mTHPC upon two-photon excitation is established. To test the photo- activity of the photosensitizer, human colon carcinoma cells, HCT-116, were incubated with 2 {mu} g/ml of mTHPC- CMPEG4 in the nutrition medium. Subsequent pulsed laser irradiation at 784 nm focused down on growing cell monolayers restricts cell vitality clearly within 24 hours after irradiation. To investigate whether an anoxic or euoxic energy transfer mechanism is involved, a uric acid assay was performed to test for the generation of singlet oxygen. Upon single-photon excitation mTHPC-CMPEG4 in TriPEG decomposed uric acid via the generation of singlet oxygen. Using femtosecond pulsed laser irradiation no decomposition of the uric acid was found, implying an anoxic energy transfer mechanism after tow-photon excitation. However, at present, we cannot exclude local hyperthermic effects in the cells containing the photosensitizer to contribute to the photodynamic activity upon two-photon excitation

Post-exercise urinary alpha-1 acid glycoprotein is not dependent on hypoxia

Proteinuria is a transient physiological phenomenon that occurs with a range of physical activities and during ascent to altitude. Exercise intensity appears to dictate the magnitude of postexercise proteinuria; however, evidence also indicates the possible contributions from exercise-induced hypoxemia or reoxygenation. Using an environmental hypoxic chamber, this crossover-designed study aimed to evaluate urinary alpha-1 acid glycoprotein (α1-AGP) excretion pre/postexercise performed in hypoxia (HYP) and normoxia (NOR). Sixteen individuals underwent experimental sessions in normoxia (NOR, 20.9% O(2)) and hypoxia (HYP, 12.0% O(2)). Sessions began with a 2-h priming period before completing a graded maximal exercise test (GXT) on a cycle ergometer, which was followed by continuation of exposure for an additional 2 h. Physiological responses (i.e., blood pressure, heart rate, and peripheral oxygenation), Lake Louise Scores (LLSs), and urine specimens (analyzed for albumin and α1-AGP) were collected pre- and postexercise (after 30, 60, and 120 min). Peak power output was significantly reduced in HYP (193 ± 45 W) compared with NOR (249 ± 59 W, P 0.05). Changes in urinary α1-AGP from pre- to post-30 min were not related to physiological responses or performance outcomes observed during GXT in NOR or HYP. Despite profound systemic hypoxemia with maximal exercise in hypoxia, postexercise α1-AGP excretion was not elevated above the levels observed following normoxic exercise. NEW & NOTEWORTHY By superimposing hypoxic exposure and maximal exercise, we were able to investigate the impact of hypoxia on postexercise proteinuria. Urinalysis for α1-AGP (via particle-enhanced immunoturbidimetry) in specimens collected pre-/postexercise enabled the sensitive detection of altered glomerular permeability. Data indicated that exercise intensity, rather than the degree of exercise-induced hypoxemia, determines postexercise proteinuria