Red Bull Increases Heart Rate at Near Sea Level and Pulmonary Shunt Fraction at High Altitude in a Porcine Model.

Red Bull energy drink is popular among athletes, students and drivers for stimulating effects or enhancing physical performance. In previous work, Red Bull has been shown to exert manifold cardiovascular effects at rest and during exercise. Red Bull with caffeine as the main ingredient increases blood pressure in resting individuals, probably due to an increased release of (nor)-epinephrine. Red Bull has been shown to alter heart rate or leaving it unchanged. Little is known about possible effects of caffeinated energy drinks on pulmonary ventilation/perfusion distribution at sea level or at altitude. Here, we hypothesized a possible alteration of pulmonary blood flow in ambient air and in hypoxia after Red Bull consumption. We subjected eight anesthetized piglets in normoxia (FiO2 = 0.21) and in hypoxia (FiO2 = 0.13), respectively, to 10 mL/kg Red Bull ingestion. Another eight animals served as controls receiving an equivalent amount of saline. In addition to cardiovascular data, ventilation/perfusion distribution of the lung was assessed by using the multiple inert gas elimination technique (MIGET). Heart rate increased in normoxic conditions but was not different from controls in acute short-term hypoxia after oral Red Bull ingestion in piglets. For the first time, we demonstrate an increased fraction of pulmonary shunt with unchanged distribution of pulmonary blood flow after Red Bull administration in acute short-term hypoxia. In summary, these findings do not oppose moderate consumption of caffeinated energy drinks even at altitude at rest and during exercise.

Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review.

Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis-like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed.

Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model.

BACKGROUND: Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model. METHODS: Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology. RESULTS: Arterial pressure of oxygen (PaO2) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 105) CFU/ml for NaCl treated pigs (p = 0.4159). CONCLUSIONS: Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.

Tolerability of inhaled N-chlorotaurine in the pig model.

BACKGROUND: N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model. METHODS: Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH4Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed. RESULTS: Arterial pressure of oxygen (PaO2) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 +/- 9.6 mmHg vs. 76 +/- 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2) (p = 0.004). Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH4Cl (p = 0.05).Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was similar to that known from other body cells (0.25-0.5 mM). CONCLUSION: The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.

Increase in alveolar antioxidant levels in hyperoxic and anoxic ventilated rabbit lungs during ischemia.

Increases in free radicals are believed to play a central role in the development of pulmonary ischemia/reperfusion (I-R) injury, leading to microvascular leakage and deterioration of pulmonary surfactant. Continued ventilation during ischemia offers significant protection against I-R injury, but the impact of alveolar oxygen supply both on lung injury and on radical generation is still unclear. We investigated the influence of hyperoxic (95% O2) and anoxic (0% O2) ventilation during ischemia on alveolar antioxidant status and surfactant properties in isolated rabbit lungs. Normoxic and hyperoxic ventilated, buffer-perfused lungs (n = 5 or 6) and native lungs (n = 6) served as controls. As compared with controls, biophysical and biochemical surfactant properties were not altered in anoxic as well as hyperoxic ventilated ischemic (2, 3, and 4 h) lungs. Assessment of several antioxidants (reduced glutathione (GSH), alpha-tocopherol (vitamin E), retinol (vitamin A), ascorbic acid (vitamin C), uric acid, and plasmalogens (1-O-alkenyl-2-acyl-phospholipids)) in bronchoalveolar lavage fluid (BALF) revealed a significant increase in antioxidant compounds under anoxic and hyperoxic ventilation, with maximum levels occuring after 3 h of ischemia. For example, GSH increased to 5.1 +/- 0.8 microM (mean +/- SE, p <.001) after 3 h of anoxic ventilated ischemia and to 2.7 +/- 0.2 microM (p <.01) after hyperoxic ventilated ischemia compared with native controls (1.3 +/- 0.2 microM), but did not significantly change under anoxic and hyperoxic ventilation alone. In parallel, under ischemic conditions, oxidized glutathione (GSSG) increased during hyperoxic (3 h: 0.81 +/- 0.04 microM, p <.001), but remained unchanged during anoxic (3 h: 0.31 +/- 0.04 microM) ventilation compared with native controls (0.22 +/- 0.02 microM), whereas F2-isoprostanes were elevated under both hyperoxic (3 h: 63 +/- 15 pM, p <.01) and anoxic (3 h: 50 +/- 9 pM, p <.01) ventilation compared with native controls (16 +/- 4 pM). We conclude that oxidative stress is increased in the lung alveolar lining layer during ischemia, during both anoxic and hyperoxic ventilation. This is paralleled by an increase rather than a decrease in alveolar antioxidant levels, suggested to reflect an adaptive response to oxidative stress during ischemia.

External cardiac defibrillation does not cause acute histopathological changes typical of thermal injuries in pigs with in situ cerebral stimulation electrodes.

UNLABELLED: Parkinson's disease patients with long-term L-dopa syndrome may benefit from an implanted cerebral stimulation device. When advanced life support demands cardioversion or defibrillation in these patients, undesired effects of monophasic electroshocks might occur in brain tissue adjacent to the stimulation electrodes (e.g., thermal injury), but also in the stimulation device itself. Thus, in this animal study (n = 6 pigs), we investigated the effects of repeated defibrillation (2 x 200 J [n = 1] and 2 x 360 J [n = 5]) at the implantation site of cerebral stimulation electrodes and on stimulation device function. Repeated external cardiac defibrillation did not cause acute histopathologic changes typical of thermal injury to brain tissue adjacent to the cerebral stimulation electrodes. Functionality of the stimulator device after defibrillation, however, ranged from normal to total loss of function. Therefore, when defibrillation is performed, the greatest possible distance between the defibrillation site and the stimulator device implantation site should be considered. Subsequent testing of the stimulator device's function is mandatory. IMPLICATIONS: Repeated cardiac defibrillation did not cause histopathologic changes typical of thermal injury at the implantation site of cerebral stimulation electrodes. The function of the stimulator device after defibrillation, however, ranged from normal to total loss of function.

Acute pain is underassessed in out-of-hospital emergencies.

OBJECTIVES: To evaluate the quality of pain assessment by emergency medical services (EMS) in out-of-hospital emergencies. METHODS: A prospective study was conducted on a convenience sample of patients during a one-year observation period. Pain ratings assessed by emergency patients were documented at three different intervals during the emergency call, and compared with concomitant assessments by EMS providers. A visual analog scale (VAS) and a verbal pain scale (VPS) were used for pain assessment. Repeated-measures ANOVA and Dunnett's t-test were used for data analysis. RESULTS: Fifty-one out of 70 eligible patients met inclusion criteria. In most emergency patients the intensity of pain was underestimated by EMS, especially when pain was severe (p = 0.0001). During the course of transport, both pain and pain assessment by EMS improved significantly (p = 0.0001). The VAS and VPS were significantly correlated (p = 0.0001). CONCLUSIONS: EMS providers significantly underestimate their patients' pain severity. EMS providers should be more attentive to their patients' complaints and comfort.

The influence of hyperoxia on regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and cerebral blood flow velocity in the middle cerebral artery (CBFVMCA) in human volunteers.

Conflicting results reported on the effects of hyperoxia on cerebral hemodynamics have been attributed mainly to methodical and species differences. In the present study contrast-enhanced magnetic resonance imaging (MRI) perfusion measurement was used to analyze the influence of hyperoxia (fraction of inspired oxygen (FiO2) = 1.0) on regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) in awake, normoventilating volunteers (n = 19). Furthermore, the experiment was repeated in 20 volunteers for transcranial Doppler sonography (TCD) measurement of cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)). When compared to normoxia (FiO2 = 0.21), hyperoxia heterogeneously influenced rCBV (4.95 +/- 0.02 to 12.87 +/- 0.08 mL/100g (FiO2 = 0.21) vs. 4.50 +/- 0.02 to 13.09 +/- 0.09 mL/100g (FiO2 = 1.0). In contrast, hyperoxia diminished rCBF in all regions (68.08 +/- 0.38 to 199.58 +/- 1.58 mL/100g/min (FiO2 = 0.21) vs. 58.63 +/- 0.32 to 175.16 +/- 1.51 mL/100g/min (FiO2 = 1.0)) except in parietal and left frontal gray matter. CBFV(MCA) remained unchanged regardless of the inspired oxygen fraction (62 +/- 9 cm/s (FiO2 = 0.21) vs. 64 +/- 8 cm/s (FiO2 = 1.0)). Finding CBFV(MCA) unchanged during hyperoxia is consistent with the present study's unchanged rCBF in parietal and left frontal gray matter. In these fronto-parietal regions predominantly fed by the middle cerebral artery, the vasoconstrictor effect of oxygen was probably counteracted by increased perfusion of foci of neuronal activity controlling general behavior and arousal.