Acetazolamide and inhaled carbon dioxide reduce periodic breathing during exercise in patients with chronic heart failure

Background Periodic breathing (PB) during sleep and exercise in heart failure (HF) is related to respiratory acid-base status, CO2 chemosensitivity, and temporal dynamics of CO2 and O2 sensing. We studied inhaled CO2 and acetazolamide to alter these factors and reduce PB. Methods and Results We measured expired and arterial gases and PB amplitude and duration in 20 HF patients during exercise before and after acetazolamide given acutely (500 mg intravenously) and prolonged (24 hours, 2 g orally), and we performed overnight polysomnography. We studied CO2 inhalation (1%-2%) during constant workload exercise. PB disappeared in 19/20 and 2/7 patients during 2% and 1% CO2. No changes in cardiorespiratory parameters were observed after acute acetazolamide. With prolonged acetazolamide at rest: ventilation +2.04 \ub1 4.0 L/min (P =.001), tidal volume +0.11 \ub1 1.13 L (P =.003), respiratory rate +1.24 \ub1 4.63 breaths/min (NS), end-tidal PO2 +4.62 \ub1 2.43 mm Hg (P =.001), and end-tidal PCO2 -2.59 \ub1 9.7 mm Hg (P <.001). At maximum exercise: Watts -10% (P <.02), VO2 -61 \ub1 109 mL/min (P =.04) and VCO2 101 \ub1 151 mL/min (P <.02). Among 20 patients, PB disappeared in 1 and 7 subjects after acute and prolonged acetazolamide, respectively. PB was present 80% \ub1 26, 65% \ub1 28, and 43% \ub1 39 of exercise time before and after acute and prolonged acetazolamide, respectively. Overnight apnea/hypopnea index decreased from 30.8 \ub1 83.8 to 21.1 \ub1 16.9 (P =.003). Conclusions In HF, inhaled CO2 and acetazolamide reduce exercise PB with additional benefits of acetazolamide on sleep PB

Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions : A joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine

The travelling options currently available allow an increasingly large number of individuals, including sedentary people, the elderly and diseased patients, to reach high altitude (HA) locations, defined as locations higher than 2500 m above sea level (asl),1S i.e. the altitude above which many of the physiological responses that represent challenges for the human body start developing. Physiological acclimatization mechanisms impose an increased workload on the cardiovascular system, but the actual risk of adverse cardiovascular events associated with HA exposure is still a debated issue. The aim of this article is to review the available evidence on the effects of HA in cardiovascular patients and to address their risk of developing clinically relevant events. This was done through multiple Medline searches on the PubMed database, with the main aim of promoting a generally safe access to mountains. Searched terms included a combination of either ‘high altitude’ or ‘hypobaric hypoxia’ plus each of the following: ‘physiology’, ‘maladaption’, ‘cardiovascular response’, ‘systemic hypertension’, ‘pulmonary hypertension’, ‘ischaemic heart disease’, ‘cardiac revascularisation’, ‘heart failure’, ‘congenital heart disease’, ‘arrhythmias’, ‘implantable cardiac devices’, ‘stroke’, ‘cerebral haemorrhage’, ‘exercise’, ‘sleep apnea’. Compared with a previous review article on this topic,2S we now include the most recent data on hypoxia-induced changes in left ventricular (LV) systolic and diastolic function, lung function and ventilation control, blood coagulation, and on the effects of pharmacological interventions. We also offer an update on the clinical and pathophysiological findings related to the exposure to altitude of patients with pre-existing cardiovascular conditions (ischaemic heart disease, heart failure, and arterial and pulmonary hypertension).</p

Strengthening altitude knowledge: a delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude

Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatment of acute-altitude illness for experts, but essential knowledge for laypersons traveling to high altitudes has not been defined. We sought expert consensus on the essential knowledge required for people planning to travel to high altitudes. Methods: The Delphi method was used. The panel consisted of two moderators, a core expert group and a plenary expert group. The moderators made a preliminary list of statements defining the desired minimum knowledge for laypersons traveling to high altitudes, based on the relevant literature. These preliminary statements were then reviewed, supplemented, and modified by a core expert group. A list of 33 statements was then presented to a plenary group of experts in successive rounds. Results: It took three rounds to reach a consensus. Of the 10 core experts invited, 7 completed all the rounds. Of the 76 plenary experts, 41 (54%) participated in Round 1, and of these 41 a total of 32 (78%) experts completed all three rounds. The final list contained 28 statements in 5 categories (altitude physiology, sleeping at altitude, AMS, HACE, and HAPE). This list represents an expert consensus on the desired minimum knowledge for laypersons planning high-altitude travel. Conclusion: Using the Delphi method, the STrengthening Altitude Knowledge initiative yielded a set of 28 statements representing essential learning objectives for laypersons who plan to travel to high altitudes. This list could be used to develop educational interventions

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Flying to high-altitude destinations: is the risk of acute mountain sickness greater?

Altitude sojourns increasingly attract individuals of all ages and different health status due to the appeal of high-altitude destinations worldwide and easy access to air travel. The risk of acute mountain sickness (AMS) when flying to high altitude destinations remains underemphasized. Thus, this mini-review aims to evaluate the altitude-dependent AMS incidence depending on the mode of ascending, e.g. by air versus terrestrial travel. A literature search was performed to identify observational studies assessing AMS incidence after acute ascent of primarily healthy adults to real high altitude. In addition, placebo arms of interventional trials evaluating the prophylactic efficacy of various drugs have been separately analysed to confirm or refute the findings from the observational studies. Linear regression analyses were used to evaluate altitude-dependent AMS incidence. Findings of 12 observational studies, in which the AMS incidence in 11 021 individuals ascending to 19 different altitudes (2200-4559 m) was evaluated, revealed an impressive 4.5-fold steeper increase in the AMS incidence for air travel as compared to slower ascent modes, i.e. hiking or combined car and/or air travel and hiking. The higher AMS incidence following transportation by flight versus slower means was also confirmed in placebo-treated participants in 10 studies of drug prophylaxis against AMS. Due to the short time span in going from low to high altitude, reduced acclimatization likely is the main reason for a higher AMS risk when travelling to high altitude destinations by flight. To avoid frustrating travel experiences and health risks, appropriate and timely medical advice on how to prepare for air travel to high-altitude is of vital importance. Effective preparation options include the use of modern pre-acclimatization strategies and pharmacological prophylaxis by acetazolamide or dexamethasone, or even considering alternate itineraries with more gradual ascent

An investigation of the role of carbonic anhydrase in aquatic and aerial gas transfer in the African lungfish Protopterus dolloi

10.1242/jeb.01780Journal of Experimental Biology208193805-3815JEBI

No renal dysfunction or salt and water retention in acute mountain sickness at 4,559 m among young resting males after passive ascent.

This study examined the role and function of the kidney at high altitude in relation to fluid balance and the development of acute mountain sickness (AMS), avoiding confounders that have contributed to conflicting results in previous studies. We examined 18 healthy male resting volunteers (18-40 yr) not acclimatized to high altitude while on a controlled diet for 24 h at Lausanne (altitude: 560 m) followed by a period of 44 h after reaching the Regina Margherita hut (4,559 m) by helicopter. AMS scores peaked after 20 h at 4,559 m. AMS was defined as functional Lake Louise score ≥ 2. There were no significant differences between 10 subjects with and 8 subjects without AMS for urinary flow, fluid balance, and weight change. Sodium excretion rate was lower in those with AMS after 24 h at altitude. Microalbuminuria increased at altitude but was not different between the groups. Creatinine clearance was not affected by altitude or AMS, whereas clearances of sinistrin and p-aminohippuric acid decreased slightly, somewhat more in those without AMS. Plasma concentrations of epinephrine, norepinephrine, atrial natriuretic factor, and vasopressin increased whereas renin activity, angiotensin, and aldosterone decreased at altitude. Circulating hormone concentrations did not differ between those with and without AMS. Summarizing, in healthy resting young men flown by helicopter to 4,559 m, renal function was not affected by hypoxia except for minor microalbuminuria, high altitude diuresis did not occur, and AMS was not associated with salt and water retention or renal dysfunction.NEW &amp; NOTEWORTHY Kidney function remained essentially unaffected and acute mountain sickness (AMS) was not associated with salt and water retention in healthy young men flown to and resting at the Margherita hut (4,559 m) under strictly controlled conditions maintaining water, salt, and food intake at pre-exposure levels. Thus, renal dysfunction and fluid retention are not essential factors contributing to the pathophysiology of AMS