The physiological and molecular effects of elevated CO<sub>2</sub>levels

Azzam, Zaher S.; Sharabi, Kfir; Guetta, Julia; Bank, Erin M.; Gruenbaum, Yosef

doi:10.4161/cc.9.8.11196

Cited by 17 publications

(14 citation statements)

References 35 publications

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“…Therefore, it is possible that intermittent hypercapnia may play a crucial role in promoting the evolution of PA atherosclerosis. Hypercapnia has both protective and deleterious effects (32). On the one hand, hypercapnia can inhibit hypoxia pulmonary vascular remodeling (33) and prevent hypoxia-induced pulmonary hypertension (34).…”

Section: Discussionmentioning

confidence: 99%

Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide

Xue¹,

Zhou²,

Poulsen³

et al. 2017

Am J Respir Cell Mol Biol

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Obstructive sleep apnea (OSA) is a common disorder characterized by intermittent hypoxia and hypercapnia (IHC) during sleep. OSA has been shown to be a risk factor for atherosclerosis, but the relation of IHC to the induction or progression of atherosclerosis is not well understood. To dissect the mechanisms involved, we compared atherosclerotic lesion formation in two mouse models, i.e., apolipoprotein E (ApoE) and low density lipoprotein receptor (Ldlr)-deficient mice, with or without IHC exposure. Ten-week-old ApoE or Ldlr mice were fed a high-fat diet for 4 or 8 weeks while being exposed to IHC for 10 hours/day or room air (RA) for 24 hours/day. En face lesions of the aorta, aortic arch, and pulmonary artery (PA) were examined. Moreover, 3,3-dimethyl-1-butanol (DMB), an inhibitor of microbial trimethylamine (TMA) production, was used to determine the contribution of TMA-oxide (TMAO) to IHC-induced atherosclerosis. Eight weeks of IHC exposure expedited the formation of atherosclerosis in both the PA and aortic arch of ApoE mice, but only in the PA of Ldlr mice (ApoE PA 8 wk, IHC 35.4 ± 1.9% versus RA 8.0 ± 2.8%, P < 0.01). The atherosclerotic lesions evolved faster and to a more severe extent in ApoE mice as compared with Ldlr mice (PA IHC 8 wk, ApoE 35.4 ± 1.9% versus Ldlr 8.2 ± 1.5%, P < 0.01). DMB significantly attenuated but did not totally eliminate IHC-induced PA atherosclerosis. Our findings suggest that IHC, a hallmark of OSA, accelerates the progression of atherosclerosis in the aorta and especially in the PA. This process is partly inhibited by DMB, demonstrating that microbial metabolites may serve as therapeutic targets for OSA-induced atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide

Xue¹,

Zhou²,

Poulsen³

et al. 2017

Am J Respir Cell Mol Biol

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“…Elevated CO 2 levels can impose severe physiological stress on complex aerobic organisms (Pörtner et al 2004;Wittmann & Pörtner 2013). Physiological responses to elevated CO 2 (hypercapnia) can be complex-often interacting across molecular, cellular, and organismal scales (Azzam et al 2010)-but are most often regulated by respiratory acidosis and associated changes to ion buffering in internal fluids (Permentier et al 2017). High atmospheric CO 2 also alters oceanic chemistry by lowering marine pH, with deleterious impacts on calcifying organisms and organisms that cannot effectively buffer internal pH (Wittmann & Pörtner 2013;Goodwin et al 2014;Bennett et al 2017).…”

Section: Requirements Of Complex Life and Co 2 Levels In The Hzmentioning

confidence: 99%

A Limited Habitable Zone for Complex Life

Schwieterman

Reinhard

Olson

et al. 2019

ApJ

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The habitable zone (HZ) is commonly defined as the range of distances from a host star within which liquid water, a key requirement for life, may exist on a planet's surface. Substantially more CO 2 than present in Earth's modern atmosphere is required to maintain clement temperatures for most of the HZ, with several bars required at the outer edge. However, most complex aerobic life on Earth is limited by CO 2 concentrations of just fractions of a bar. At the same time, most exoplanets in the traditional HZ reside in proximity to M dwarfs, which are more numerous than Sun-like G dwarfs but are predicted to promote greater abundances of gases that can be toxic in the atmospheres of orbiting planets, such as carbon monoxide (CO). Here we show that the HZ for complex aerobic life is likely limited relative to that for microbial life. We use a 1D radiative-convective climate and photochemical models to circumscribe a Habitable Zone for Complex Life (HZCL) based on known toxicity limits for a range of organisms as a proof of concept. We find that for CO 2 tolerances of 0.01, 0.1, and 1 bar, the HZCL is only 21%, 32%, and 50% as wide as the conventional HZ for a Sun-like star, and that CO concentrations may limit some complex life throughout the entire HZ of the coolest M dwarfs. These results cast new light on the likely distribution of complex life in the universe and have important ramifications for the search for exoplanet biosignatures and technosignatures.

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“…The impact of hypercapnia on lung injury or on systemic effects including remote organ damage (myocardial insufficiency, renal failure, and hepatic/intestinal ischemia) is somewhat controversial [7, 8], delaying or preventing the implementation of adequate lung-protective strategies [9]. …”

Section: Introductionmentioning

confidence: 99%

Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS

et al. 2013

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BackgroundAcute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (VT) strategy (VT ≈ 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS.MethodsSeventy-nine patients were enrolled after a ‘stabilization period’ (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low VT ventilation (≈3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (≈6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality.ResultsVentilation with very low VT’s was easy to implement with extracorporeal CO2-removal. VFD’s within 60 days were not different between the study group (33.2 ± 20) and the control group (29.2 ± 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 ≤150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 ± 12.8) compared to control (28.2 ± 16.4, p = 0.033). The mortality rate was low (16.5 %) and did not differ between groups.ConclusionsThe use of very low VT combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a ‘normal’ lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928).Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-012-2787-6) contains supplementary material, which is available to authorized users.

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The physiological and molecular effects of elevated CO₂levels

Cited by 17 publications

References 35 publications

Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide

Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide

A Limited Habitable Zone for Complex Life

Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS

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The physiological and molecular effects of elevated CO2levels

Cited by 17 publications

References 35 publications

Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide

Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide

A Limited Habitable Zone for Complex Life

Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS

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The physiological and molecular effects of elevated CO₂levels