Carotid chemoreceptors have a limited role in mediating the hyperthermia-induced hyperventilation in exercising humans.

Hyperthermia causes hyperventilation at rest and during exercise. We previously reported that carotid chemoreceptors partly contribute to the hyperthermia-induced hyperventilation at rest. However, given that a hyperthermia-induced hyperventilation markedly differs between rest and exercise, the results obtained at rest may not be representative of the response in exercise. Therefore, we evaluated whether carotid chemoreceptors contribute to hyperthermia-induced hyperventilation in exercising humans. Eleven healthy young men (23 ± 2 yr) cycled in the heat (37°C) at a fixed submaximal workload equal to ~55% of the individual's predetermined peak oxygen uptake (moderate intensity). To suppress carotid chemoreceptor activity, 30-s hyperoxia breathing (100% O2) was performed at rest (before exercise) and during exercise at increasing levels of hyperthermia as defined by an increase in esophageal temperature of 0.5°C (low), 1.0°C (moderate), 1.5°C (high), and 2.0°C (severe) above resting levels. Ventilation during exercise gradually increased as esophageal temperature increased (all P ≤ 0.05), indicating that hyperthermia-induced hyperventilation occurred. Hyperoxia breathing suppressed ventilation in a greater manner during exercise (-9 to -13 l/min) than at rest (-2 ± 1 l/min); however, the magnitude of reduction during exercise did not differ at low (0.5°C) to severe (2.0°C) increases in esophageal temperature (all P > 0.05). Similarly, hyperoxia-induced changes in ventilation during exercise as assessed by percent change from prehyperoxic levels were not different at all levels of hyperthermia (~15-20%, all P > 0.05). We show that in young men carotid chemoreceptor contribution to hyperthermia-induced hyperventilation is relatively small at low-to-severe increases in body core temperature induced by moderate-intensity exercise in the heat. NEW & NOTEWORTHY Exercise-induced increases in hyperthermia cause a progressive increase in ventilation in humans. However, the mechanisms underpinning this response remain unresolved. We showed that in young men hyperventilation associated with exercise-induced hyperthermia is not predominantly mediated by carotid chemoreceptors. This study provides important new insights into the mechanism(s) underpinning the regulation of hyperthermia-induced hyperventilation in humans and suggests that factor(s) other than carotid chemoreceptors play a more important role in mediating this response.

Elevated potassium outward currents in hyperoxia treated atrial cardiomyocytes.

Supplementation of 100% oxygen is a very common intervention in intensive care units (ICU) and critical care centers for patients with dysfunctional lung and lung disorders. Although there is advantage in delivering sufficient levels of oxygen, hyperoxia is reported to be directly associated with increasing in-hospital deaths. Our previous studies reported ventricular and electrical remodeling in hyperoxia treated mouse hearts, and in this article, for the first time, we are investigating the effects of hyperoxia on atrial electrophysiology using whole-cell patch-clamp electrophysiology experiments along with assessment of Kv1.5, Kv4.2, and KChIP2 transcripts and protein profiles using real-time quantitative RT-PCR and Western blotting. Our data showed that induction of hyperoxia for 3 days in mice showed larger outward potassium currents with shorter action potential durations (APD). This increase in current densities is due to significant increase in ultrarapid delayed rectifier outward K+ currents (IKur ) and rapidly activating, rapidly inactivating transient outward K+ current (Ito ) densities. We also observed a significant increase in both transcripts and protein levels of Kv1.5 and KChIP2 in hyperoxia treated atrial cardiomyocytes, whereas no significant change was observed in Kv4.2 transcripts or protein. The data presented here further support our previous findings that hyperoxia induces not only ventricular remodeling, but also atrial electrical remodeling.

Sublingual microvascular perfusion is altered during normobaric and hyperbaric hyperoxia.

Hyperoxia and hyperbaric oxygen therapy can restore oxygen tensions in tissues distressed by ischemic injury and poor vascularization and is believed to also yield angiogenesis and regulate tissue perfusion. The aim of this study was to develop a model in which hyperoxia-driven microvascular changes could be quantified and to test the hypothesis that microcirculatory responses to both normobaric (NB) and hyperbaric (HB) hyperoxic maneuvers are reversible. Sublingual mucosa microcirculation vessel density, proportion of perfused vessels, vessel diameters, microvascular flow index, macrohemodynamic, and blood gas parameters were examined in male rabbits breathing sequential O2/air mixtures of 21%, 55%, 100%, and return to 21% during NB (1.0 bar) and HB (2.5 bar) conditions. The results indicate that NB hyperoxia (55% and 100%) produced significant decreases in microvascular density and vascular diameters (p<0.01 and p<0.05, respectively) accompanied by significant increases in systolic and mean arterial blood pressure (p<0.05, respectively) with no changes in blood flow indices when compared to NB normoxia. HB normoxia/hyperoxia resulted in significant decreases in microvascular density (p<0.05), a transient rise in systolic blood pressure at 55% (p<0.01), and no changes in blood vessel diameter and blood flow indices when compared to NB hyperoxia. All microcirculation parameters reverted back to normal values upon return to NB normoxia. We conclude that NB/HB hyperoxia-driven changes elicit reversible physiological control of sublingual mucosa blood perfusion in the presence of steady cardiovascular function and that the absence of microvascular vasoconstriction during HB conditions suggests a beneficial mechanism associated with maintaining peak tissue perfusion states.

Neurotoxic effects of oxygen in hyperbaric environment: A case report.

INTRODUCTION: Oxygen is an essential element of life in aerobic organisms. However, if not controlled, inhalation of oxygen under increased pressure in conditions of hyperbaric oxygen therapy can lead to serious damage and even death. CASE REPORT: We presented a 20-year-old male who had begun exhibiting symptoms of epilepsy during diving test in a hyperbaric chamber while inhaling 100% oxygen. He was immediately taken off oxygen mask and started breathing air and began rapid decompression. He lost consciousness, began foaming at the mouth, and had a series of tonic spasms. The patient was previously completely healthy and not on any medications. He was admitted for emergency treatment in our hospital, where he was treated for epilepsy. On admission, he complained of muscle and joint pain, and had erythematous changes on the forehead, neck and chest. All these changes occurred after leaving the hyperbaric chamber. Bloodwork revealed leukocytosis with neutrophil (Leukocytosis 16.0 x 10(9)/L (reference values 4.00-11.00 x 10(9)/L), Neutrophili 13 x 10(9)/L (reference values 1.9-8.0 x 10(9)/L), with elevated enzymes aspartate aminotransferase (AST) 56 U/L (reference values 0-37 U/L), alanin aminotransferase (ALT) 59 U/L, (reference values 25-65 U/L), creatine kinase (CK) 649 U/L, (reference values 32-300 U /L), lactate dehydrogenase (LDH) 398 U/L (reference values 85-227 U/L). Because of pain and his condition we began treatment in a hyperbaric chamber at a pressure of 2.0 ATA for 70 minutes, resulting in a reduction of symptoms and objective recovery of the patient. Within 24 h, repeated laboratory tests showed a reduction of leukocytosis (13 x 109/L and neutrophils (7.81 x 109/L), and the gradual reduction of the enzymes AST (47 U/L), ALT (50 U/L, CK (409 U/L), LDH (325 U/L). Since head CT and EEG were normal, epilepsy diagnosis was ruled out. This fact, along with medical tests, facilitated the differential diagnosis and confirmed that this was a case of neurotoxic effects of oxygen while the patient was in a hyperbaric chamber, not epileptic seizures. CONCLUSION: This case report suggests that in patients with symptoms of epileptic seizures while undergoing treatment in a hyperbaric chamber, it is always important to think of neurotoxic effects of pure oxygen which occurs at higher pressures and with a longer inhalation of 100% oxygen. In these patients, reexposure to hyperbaric conditions leads to recovery. This effect is important in daily inhalation of 100% oxygen under hyperbaric conditions which is why the use of pure oxygen is controlled and diving is allowed in shallow depths and for a limited time.

Supplementary oxygen for nonhypoxemic patients: O2 much of a good thing?

Supplementary oxygen is routinely administered to patients, even those with adequate oxygen saturations, in the belief that it increases oxygen delivery. But oxygen delivery depends not just on arterial oxygen content but also on perfusion. It is not widely recognized that hyperoxia causes vasoconstriction, either directly or through hyperoxia-induced hypocapnia. If perfusion decreases more than arterial oxygen content increases during hyperoxia, then regional oxygen delivery decreases. This mechanism, and not (just) that attributed to reactive oxygen species, is likely to contribute to the worse outcomes in patients given high-concentration oxygen in the treatment of myocardial infarction, in postcardiac arrest, in stroke, in neonatal resuscitation and in the critically ill. The mechanism may also contribute to the increased risk of mortality in acute exacerbations of chronic obstructive pulmonary disease, in which worsening respiratory failure plays a predominant role. To avoid these effects, hyperoxia and hypocapnia should be avoided, with oxygen administered only to patients with evidence of hypoxemia and at a dose that relieves hypoxemia without causing hyperoxia.

Hyperoxia sensing: from molecular mechanisms to significance in disease.

Oxygen therapy using mechanical ventilation with hyperoxia is necessary to treat patients with respiratory failure and distress. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), causing cellular damage and multiple organ dysfunctions. As the lungs are directly exposed, hyperoxia can cause both acute and chronic inflammatory lung injury and compromise innate immunity. ROS may contribute to pulmonary oxygen toxicity by overwhelming redox homeostasis, altering signaling cascades that affect cell fate, ultimately leading to hyperoxia-induced acute lung injury (HALI). HALI is characterized by pronounced inflammatory responses with leukocyte infiltration, injury, and death of pulmonary cells, including epithelia, endothelia, and macrophages. Under hyperoxic conditions, ROS mediate both direct and indirect modulation of signaling molecules such as protein kinases, transcription factors, receptors, and pro- and anti-apoptotic factors. The focus of this review is to elaborate on hyperoxia-activated key sensing molecules and current understanding of their signaling mechanisms in HALI. A better understanding of the signaling pathways leading to HALI may provide valuable insights on its pathogenesis and may help in designing more effective therapeutic approaches.

Oxygen therapy-use and abuse in acute myocardial infarction patients.

In August 2008, an article was published in Heart entitled, "The Routine Use of Oxygen in the Treatment of Myocardial Infarction." This article stimulated me to opine on this topic, which has been an interest of mine for many years.

Two faces of nitric oxide: implications for cellular mechanisms of oxygen toxicity.

Recent investigations have elucidated some of the diverse roles played by reactive oxygen and nitrogen species in events that lead to oxygen toxicity and defend against it. The focus of this review is on toxic and protective mechanisms in hyperoxia that have been investigated in our laboratories, with an emphasis on interactions of nitric oxide (NO) with other endogenous chemical species and with different physiological systems. It is now emerging from these studies that the anatomical localization of NO release, which depends, in part, on whether the oxygen exposure is normobaric or hyperbaric, strongly influences whether toxicity emerges and what form it takes, for example, acute lung injury, central nervous system excitation, or both. Spatial effects also contribute to differences in the susceptibility of different cells in organs at risk from hyperoxia, especially in the brain and lungs. As additional nodes are identified in this interactive network of toxic and protective responses, future advances may open up the possibility of novel pharmacological interventions to extend both the time and partial pressures of oxygen exposures that can be safely tolerated. The implications of a better understanding of the mechanisms by which NO contributes to central nervous system oxygen toxicity may include new insights into the pathogenesis of seizures of diverse etiologies. Likewise, improved knowledge of NO-based mechanisms of pulmonary oxygen toxicity may enhance our understanding of other types of lung injury associated with oxidative or nitrosative stress.

B-type natriuretic peptide in healthy subjects after exposure to hyperbaric oxygen at 2.5 ATA.

INTRODUCTION: B-type natriuretic peptide (BNP) is a cardiac hormone used as a marker of cardiac dysfunction with diuretic and vasodilating properties secreted by the ventricles in response to wall stress. Hyperbaric oxygen (HBO) exposure is known to induce hemodynamic effects in humans which can be complicated by acute pulmonary edema. The aim of this study was to investigate if HBO has any effects on the secretion of BNP in healthy human subjects. METHODS: Eight healthy volunteers underwent the following HBO protocol in a hyperbaric chamber: compression to 2.5 atmospheres absolute (ATA); 45 min breathing 100% oxygen; 5 min breathing air; another 45 min in 100% oxygen; then decompression to atmospheric pressure. A venous blood sample was drawn before entering the chamber (To), immediately at the end of the treatment (T1), and at 5 h from To (T2). BNP concentration was determined using a rapid point-of-care immunoassay. Non-parametric statistics were used to analyze data. RESULTS: No difference in BNP levels was found between T0 and T1 or T2. DISCUSSION: The findings of this preliminary study show that in healthy subjects a single HBO exposure does not significantly modify BNP plasma levels. We hypothesize that this can be the net result between the stimulating effect of the HBO-induced vasoconstriction and the direct inhibitory effect on BNP secretion of myocyte hyperoxia. We conclude that HBO does not modify BNP secretion in healthy volunteers and that the direct effect of extreme hyperoxia on BNP secretion deserves further investigation.