Sublingual microcirculation in prehospital critical care medicine: A proof-of-concept study.

OBJECTIVE: Diagnostic and risk stratification are limited in emergencies. The measurement of microcirculation might identify patients with poor perfusion but compensated macrocirculation such as in beginning shock. This proof-of-concept study examines whether sublingual prehospital sidestream dark-field microscopy is feasible. METHODS: This prospective observational study included patients receiving medical aid by an emergency ambulance who had a spontaneous circulation and offered access to the sublingual mucosa. Sublingual measurement of microcirculation was performed using a sidestream dark field camera. Video quality was evaluated with microcirculation image quality score (microcirculation image quality score). AVA 4.3C software calculated microcirculatory parameters. RESULTS: Thirty patients (47% male) were included. The average age was 63 years (±20 years SD), the severity of the disease (quantified by National Advisory Committee on Aeronautics) was 3.4 (±0.7 SD). Macrocirculation presented within the normal range. The most frequent cause preventing the measurement was a time-critical disease (64%). In 17 patients (57%), the videos could be analyzed immediately. The average quality of the video was 2.2 ± 0.45 points ('acceptable'). There were minor restrictions of microcirculation. Microcirculation correlated with National Advisory Committee on Aeronautics, but not with the macrocirculation. No complications occurred. CONCLUSION: The prehospital sublingual measurement is safe and valid. Despite normal macrocirculation, microcirculation was impaired and correlated with National Advisory Committee on Aeronautics.

Dynamic Changes of Heart Failure Biomarkers in Response to Parabolic Flight.

BACKGROUND: we aimed at investigating the influence of weightlessness and hypergravity by means of parabolic flight on the levels of the heart failure biomarkers H-FABP, sST2, IL-33, GDF-15, suPAR and Fetuin-A. METHODS: 14 healthy volunteers (males: eight; mean age: 28.9) undergoing 31 short-term phases of weightlessness and hypergravity were included. At different time points (baseline, 1 h/24 h after parabolic flight), venous blood was drawn and analyzed by the use of ELISA. RESULTS: sST2 evidenced a significant decrease 24 h after parabolic flight (baseline vs. 24, p = 0.009; 1 h vs. 24 h, p = 0.004). A similar finding was observed for GDF-15 (baseline vs. 24 h, p = 0.002; 1 h vs. 24 h, p = 0.025). The suPAR showed a significant decrease 24 h after parabolic flight (baseline vs. 24 h, p = 0.1726; 1 h vs. 24 h, p = 0.009). Fetuin-A showed a significant increase at 1 h and 24 h after parabolic flight (baseline vs. 24 h, p = 0.007; 1 h vs. 24 h, p = 0.04). H-FABP and IL-33 showed no significant differences at all time points. CONCLUSION: Our results suggest a reduction in cardiac stress induced by exposure to gravitational changes. Moreover, our findings indicate an influence of gravitational changes on proliferative processes and calcium homeostasis.

[Asymptomatic bradycardia and pacemaker : To implant, or not to implant?] / Asymptomatische Bradykardien : Wann ist die Implantation eines Herzschrittmachers sinnvoll?

The cardiac implantable electronic device (CIED) is the therapy of choice for management of symptomatic bradyarrhythmias. However, the indication for CIED implantation in the cases of asymptomatic bradycardias should be carefully individualized. Incidental electrocardiographic findings in asymptomatic patients (e.g., low baseline heart rates, higher than first-degree atrioventricular block or longer pauses) may complicate the physician's decision regarding the necessity of CIED implantation. The main reason is the inherit risk of short- and long-term complications with every CIED implantation, i.e., peri-operative complications, risk of CIED infection, lead fractures, and the necessity for lead extraction. Therefore, before opting for, or against, CIED implantation, several factors should be considered in the subset of asymptomatic patients.

Assessing physical activity with the wearable cardioverter defibrillator in patients with newly diagnosed heart failure.

Background: The wearable cardioverter defibrillator (WCD), (LifeVest, ZOLL, Pittsburgh, PA, USA) is a medical device designed for the temporary detection and treatment of malignant ventricular tachyarrhythmias. WCD telemonitoring features enable the evaluation of the physical activity (PhA) of the patients. We sought to assess with the WCD the PhA of patients with newly diagnosed heart failure. Methods: We collected and analyzed the data of all patients treated with the WCD in our clinic. Patients with newly diagnosed ischemic, or non-ischemic cardiomyopathy and severely reduced ejection fraction, who were treated with the WCD for at least 28 consecutive days and had a compliance of at least 18 h the day were included. Results: Seventy-seven patients were eligible for analysis. Thirty-seven patients suffered from ischemic and 40 from non-ischemic heart disease. The average days the WCD was carried was 77.3 ± 44.6 days and the mean wearing time was 22.8 ± 2.1 h. The patients showed significantly increased PhA measured by daily steps between the first two and the last two weeks (Mean steps in the first 2 weeks: 4,952.6 ± 3,052.7 vs. mean steps in the last 2 weeks: 6,119.6 ± 3,776.2, p-value: < 0.001). In the end of the surveillance period an increase of the ejection fraction was observed (LVEF-before: 25.8 ± 6.6% vs. LVEF-after: 37.5 ± 10.6%, p < 0.001). Improvement of the EF did not correlate with the improvement of PhA. Conclusion: The WCD provides useful information regarding patient PhA and may be additionally utilized for early heart failure treatment adjustment.

Next-generation sequencing analysis of circulating micro-RNA expression in response to parabolic flight as a spaceflight analogue.

Understanding physiologic reactions to weightlessness is an indispensable requirement for safe human space missions. This study aims to analyse changes in the expression of circulating miRNAs following exposure to gravitational changes. Eight healthy volunteers (age: 24.5 years, male: 4, female: 4) were included. Each subject underwent 31 short-term phases of weightlessness and hypergravity induced by parabolic flight as a spaceflight analogue. At baseline, 1 and 24 h after parabolic flight, venous blood was withdrawn. Analysis of circulating miRNAs in serum was conducted by means of next generation sequencing. In total, 213 miRNAs were robustly detected (TPM > 5) by small RNA sequencing in all 24 samples. Four miRNAs evidenced a significant change in expression after adjusting for multiple testing. Only miR-223-3p showed a consistent significant decrease 24 h after parabolic flight compared to baseline values and values at 1 h after parabolic flight. miR-941 and miR-24-3p showed a significant decrease 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. miR-486-5p showed a significant increase 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. A target network analysis identified genes of the p53 signaling pathway and the cell cycle highly enriched among the targets of the four microRNAs. Our findings suggest cellular adaption to gravitational changes at the post-transcriptional level. Based on our results, we suggest a change in cell cycle regulation as potential explanation for adaptational changes observed in space missions.

Comprehensive Analysis of Macrocirculation and Microcirculation in Microgravity During Parabolic Flights.

BACKGROUND: Profound knowledge about cardiovascular physiology in the setting of microgravity can help in the course of preparations for human space missions. So far, influences of microgravity on the cardiovascular system have been demonstrated, particularly pertaining to venous fluid shifts. Yet, little is known about the mechanisms of these adaptations on continuous macrocirculatory level and regarding the microcirculation. METHODS: Twelve healthy volunteers were subjected to alternating microgravity and hypergravity in the course of parabolic flight maneuvers. Under these conditions, as well as in normal gravity, the sublingual microcirculation was assessed by intravital sidestream dark field microscopy. Furthermore, hemodynamic parameters such as heart rate, blood pressure, and cardiac output were recorded by beat-to-beat analysis. In these settings, data acquisition was performed in seated and in supine postures. RESULTS: Systolic [median 116 mmHg (102; 129) interquartile range (IQR) vs. 125 mmHg (109; 136) IQR, p = 0.01] as well as diastolic [median 72 mmHg (61; 79) IQR vs. 80 mmHg (69; 89) IQR, p = 0.003] blood pressure was reduced, and cardiac output [median 6.9 l/min (6.5; 8.8) IQR vs. 6.8 l/min (6.2; 8.5) IQR, p = 0.0002] increased in weightlessness compared to normal gravitation phases in the seated but not in the supine posture. However, microcirculation represented by perfused proportion of vessels and by total vessel density was unaffected in acute weightlessness. CONCLUSION: Profound changes of the macrocirculation were found in seated postures, but not in supine postures. However, microcirculation remained stable in all postures.

QTc evaluation in patients with bundle branch block.

Proper measurement of the QT interval on the 12-lead body-surface ECG is challenging in daily practice. Even more difficult is its correct estimation in the presence of repolarization abnormalities, arrhythmias or bundle-branch blocks (BBB). The QT interval results from two parts of the ECG: (1) the QRS complex, describing the excitation of the ventricles and (2) the JT interval, describing the repolarisation of the ventricles. Prolongation of the QRS width - like in the presence of BBB - entails prolongation of the QT interval, making the estimation of the true repolarisation time challenging. The US recommendations for the standardization and interpretation of the ECG suggest focusing on the JT interval in presence of BBB. However, in clinical practice physicians have become more familiar with the interpretation of QT-interval measurements than with the interpretation of the JT Interval. In the last decade, a simple formula for the estimation of the "modified QT interval" in the presence of left or right BBB has been developed and evaluated. In this formula, the modified QT interval is calculated by subtracting 50% of the length of the BBB-QRS from the measured QT interval (QTm = QTBBB - 50% QRSBBB). Subsequently, rate-correction formula should be applied as usual. In this review, we discuss the determination of the QT-interval in the presence of BBB and summarize the origin and application of the modified QT-interval formula.

Exposure to acute normobaric hypoxia results in adaptions of both the macro- and microcirculatory system.

Although acute hypoxia is of utmost pathophysiologic relevance in health and disease, studies on its effects on both the macro- and microcirculation are scarce. Herein, we provide a comprehensive analysis of the effects of acute normobaric hypoxia on human macro- and microcirculation. 20 healthy participants were enrolled in this study. Hypoxia was induced in a normobaric hypoxia chamber by decreasing the partial pressure of oxygen in inhaled air stepwisely (pO2; 21.25 kPa (0 k), 16.42 kPa (2 k), 12.63 kPa (4 k) and 9.64 kPa (6 k)). Macrocirculatory effects were assessed by cardiac output measurements, microcirculatory changes were investigated by sidestream dark-field imaging in the sublingual capillary bed and videocapillaroscopy at the nailfold. Exposure to hypoxia resulted in a decrease of systemic vascular resistance (p < 0.0001) and diastolic blood pressure (p = 0.014). Concomitantly, we observed an increase in heart rate (p < 0.0001) and an increase of cardiac output (p < 0.0001). In the sublingual microcirculation, exposure to hypoxia resulted in an increase of total vessel density, proportion of perfused vessels and perfused vessel density. Furthermore, we observed an increase in peripheral capillary density. Exposure to acute hypoxia results in vasodilatation of resistance arteries, as well as recruitment of microvessels of the central and peripheral microcirculation. The observed macro- and microcirculatory effects are most likely a result from compensatory mechanisms to ensure adequate tissue oxygenation.

Blood parameter analysis after short term exposure to weightlessness in parabolic flight.

BACKGROUND: Parabolic flights offer a unique platform for human experiments in short-term weightlessness. It is generally known that human organ systems react to changes of gravity. Yet, little is known about alterations of blood parameters under these conditions with special emphasis on blood rheology. OBJECTIVE: We investigated the alterations of distinct blood parameters after exposure to weightlessness. METHODS: 14 healthy volunteers underwent short-term phases of weightlessness induced by parabolic flight. At different time points (baseline, t2:1 hour after landing, and t3:24 hours after baseline), venous blood was drawn and analyzed. RESULTS: Analysis of red blood count revealed significant decreases of hemoglobin and hematocrit post flight. While total white blood counts were unaltered, differential subset analysis revealed significant decreases of eosinophil granulocytes and monocytes. Cortisole levels were unchanged and lacked physiologic circadian decrease. Parameters of renal function were found significantly improved (GFR (ml/min/1,73m2): Baseline: 105 [89;109], t2:117 [98;125], t3:110 [102;119]; p = 0.0013. In the sense of mild myocytolysis, levels of myoglobin were significantly elevated post-flight with fast recovery to baseline levels. CONCLUSIONS: In the current analysis, significant alterations of blood parameters after exposure to weightlessness could be detected. These results contribute to the understanding of physiologic adaptations of the human body to weightlessness.

Analysis of human microcirculation in weightlessness: Study protocol and pre-study experiments.

BACKGROUND: In weightlessness, alterations in organ systems have been reported. The microcirculation consists of a network of blood vessels with diameters of a few µm. It is considered the largest part of the circulatory system of the human body and essential for exchange of gas, nutrients and waste products. An investigation of the microcirculation in weightlessness seems warranted but has not yet been performed. OBJECTIVE: In this paper, we outline a study in which we will investigate the possible interrelations between weightlessness and microcirculation. We will induce weightlessness in the course of parabolic flight maneuvers, which will be conducted during a parabolic flight campaign. In this study protocol also an evaluation of a possible influence of parabolic flight premedication on microcirculation will be described. METHODS: The microcirculation will be investigated by sublingual intravital measurements applying sidestream darkfield microscopy. Parameters of macrocirculation such as heart rate, blood pressure and blood oxygenation will also be investigated. RESULTS: In our pre-study experiments, neither dimenhydrinate nor scopolamine altered microcirculation. CONCLUSIONS: As the application of motion sickness therapy did not alter microcirculation, it will be applied during the parabolic flight maneuvers of the campaign. Our results might deepen the understanding of microcirculation on space missions and on earth.