Biological effects of hypercapnia

Laffey, John G.; Kavanagh, Brian P.

doi:10.1007/s001340050027

Cited by 47 publications

(28 citation statements)

References 25 publications

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“…The present study adds to a growing body of experimental evidence (35,36,38,47) indicating that hypercapnia can have beneficial effects on the pulmonary circulation. Whereas there is a relatively large body of literature examining the acute pulmonary vascular effects of hypercapnia (54), we are aware of only one other study (47) where the chronic effects of hypercapnia were examined.…”

Section: Discussionmentioning

confidence: 62%

Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat

Kantores¹,

McNamara²,

Teixeira³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

108

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. Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat. Am J Physiol Lung Cell Mol Physiol 291: L912-L922, 2006. First published July 7, 2006 doi:10.1152/ajplung.00480.2005.-Induction of hypercapnia by breathing high concentrations of carbon dioxide (CO2) may have beneficial effects on the pulmonary circulation. We tested the hypothesis that exposure to CO2 would protect against chronic pulmonary hypertension in newborn rats. Atmospheric CO2 was maintained at Ͻ0.5% (normocapnia), 5.5%, or 10% during exposure from birth for 14 days to normoxia (21% O2) or moderate hypoxia (13% O2). Pulmonary vascular and hemodynamic abnormalities in animals exposed to chronic hypoxia included increased pulmonary arterial resistance, right ventricular hypertrophy and dysfunction, medial thickening of pulmonary resistance arteries, and distal arterial muscularization. Exposure to 10% CO2 (but not to 5.5% CO2) significantly attenuated pulmonary vascular remodeling and increased pulmonary arterial resistance in hypoxia-exposed animals (P Ͻ 0.05), whereas both concentrations of CO2 normalized right ventricular performance. Exposure to 10% CO2 attenuated increased oxidant stress induced by hypoxia, as quantified by 8-isoprostane content in the lung, and prevented upregulation of endothelin-1, a critical mediator of pulmonary vascular remodeling. We conclude that hypercapnic acidosis has beneficial effects on pulmonary hypertension and vascular remodeling induced by chronic hypoxia, which we speculate derives from antioxidant properties of CO2 on the lung and consequent modulating effects on the endothelin pathway. carbon dioxide; endothelin; oxidant stress; 8-isoprostane; echocardiography PULMONARY HYPERTENSION, characterized by increased pulmonary artery resistance and pressure, is a common complication of sick newborn infants that carries a high mortality and is associated with considerable long-term morbidity in survivors (43,59,60). Studies suggest that the newborn is uniquely susceptible to remodeling of pulmonary resistance arteries (49). Vascular remodeling contributes to increased resistance (15), may limit the effectiveness of vasodilator therapies (15,32), and in the newborn appears to contribute to inhibition of lung growth and alveolar development (33,45,46,57). Reversal of pathological changes in the newborn pulmonary vascular bed is also more likely to be delayed and incomplete (29,31,49), leading to an increased susceptibility to the development of more severe pulmonary hypertension in later life (10, 17). Thus therapies aimed at preventing or ameliorating vascular remodeling in the newborn have great potential to improve mortality and long-term outcome.A major pathological role for reactive oxygen species (ROS) in pulmonary hypertension is likely, as evidenced by observational studies showing increased oxidant stress in the lungs of adult humans with idiopathic pulmonary arterial hypertension (6, 13) and by the reported efficacy of various antioxidant interventions in the pr...

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Section: Discussionmentioning

confidence: 62%

Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat

Kantores¹,

McNamara²,

Teixeira³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

108

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“…5 "Permissive hypercapnia", first implemented in neonatal practice by Wung et al, 6 was demonstrated to improve survival in patients with adult respiratory distress syndrome in studies by Hickling et al 7,8 The concept of 'therapeutic hypercapnia', whereby PaCO 2 is deliberately elevated in order to attenuate endorgan injury, has evolved from studies which have demonstrated reduced tissue injury in association with hypercapnia. 9,10 Elevation of PaCO 2 attenuated injury resulting from myocardial ischemia, 11 stroke 12 and lung reperfusion 13 and has been associated with improved neurological outcome following cardiopulmonary bypass. 14 Although the mechanisms of protection have not been clearly delineated, improved balance between tissue O 2 supply and demand may play a significant role.…”

Section: Résultats : La To 2 Tc a Augmenté En Proportion De L'oxygénamentioning

confidence: 99%

“…14 Although the mechanisms of protection have not been clearly delineated, improved balance between tissue O 2 supply and demand may play a significant role. 9,10 Experimental studies help to explain how hypercapnia may improve cerebral tissue oxygenation. Although not predicted by the alveolar gas equation, elevated PaCO 2 has been demonstrated to increase arterial PaO 2 , possibly by improved ventilation perfusion matching in the lung.…”

Section: Résultats : La To 2 Tc a Augmenté En Proportion De L'oxygénamentioning

confidence: 99%

“…(48,7 ± 4,9, 72,3 ± 6,0 et 95,3 ± 15,4 mmHg), de la PaO 2 (172,2 ± 33,1, 191,7 ± 42,5 et 216,0 ± 41,8 mmHg) et de la TO 2 TC (29,1 ± 9,2, 49,4 ± 19,5 et 60,5 ± 23,0 mmHg) ont été observées avec l'augmentation des concentrations de CO 2 inspiré de 0 % à 5 %, 10 % et 15 %, respectivement, tandis que le pH s'est abaissé (P < 0,05 pour chacune). L'exposition au CO 2 a fait monter la TO 2 TC de 1,04 ± 0,67 à une valeur maximale de 1,49 ± 0,45 (P < 0,05 (34,9 ± 14,5 vs 11,4 ± 5,0 mmHg, P < 0,05 …”

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L’hypercapnie augmente la tension en oxygène du tissu cérébral chez des rats anesthésiés

Hare

Kavanagh

Mazer

et al. 2003

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : To test the hypotheses that deliberate elevation of PaCO 2 increases cerebral tissue oxygen tension (PBrO 2 ) by augmenting PaO 2 and regional cerebral blood flow (rCBF).M Me et th ho od ds s: : Anesthetized rats were exposed to increasing levels of inspired oxygen (O 2 ) or carbon dioxide (CO 2 ; 5%, 10% and 15%, n = 6). Mean arterial blood pressure (MAP), PBrO 2 and rCBF were measured continuously. Blood gas analysis and hemoglobin concentrations were determined for each change in inspired gas concentration. Data are presented as mean ± standard deviation with P < 0.05 taken to be significant. R Re es su ul lt ts s: : The PBrO 2 increased in proportion to arterial oxygenation (PaO 2 ) when the percentage of inspired O 2 was increased. Proportional increases in PaCO 2 (48.7 ± 4.9, 72.3 ± 6.0 and 95.3 ± 15.4 mmHg), PaO 2 (172.2 ± 33.1, 191.7 ± 42.5 and 216.0 ± 41.8 mmHg), and PBrO 2 (29.1 ± 9.2, 49.4 ± 19.5 and 60.5 ± 23.0 mmHg) were observed when inspired CO 2 concentrations were increased from 0% to 5%, 10% and 15%, respectively, while arterial pH decreased (P < 0.05 for each). Exposure to CO 2 increased rCBF from 1.04 ± 0.67 to a peak value of 1.49 ± 0.45 (P < 0.05). Following removal of exogenous CO 2 , arterial blood gas values returned to baseline while rCBF and PBrO 2 remained elevated for over 30 min. The hypercapnia induced increase in PBrO 2 was threefold higher than that resulting from a comparable increase in PaO 2 achieved by increasing the inspired O 2 concentration (34.9 ± 14.5 vs 11.4 ± 5.0 mmHg, P < 0.05).C Co on nc cl lu us si io on n: : These data support the hypothesis that the combined effect of increased CBF, PaO 2 and reduced pH collectively contribute to augmenting cerebral PBrO 2 during hypercapnia. (48,7 ± 4,9, 72,3 ± 6,0 et 95,3 ± 15,4 mmHg), de la PaO 2 (172,2 ± 33,1, 191,7 ± 42,5 et 216,0 ± 41,8 mmHg) et de la TO 2 TC (29,1 ± 9,2, 49,4 ± 19,5 et 60,5 ± 23,0 mmHg) ont été observées avec l'augmentation des concentrations de CO 2 inspiré de 0 % à 5 %, 10 % et 15 %, respectivement, tandis que le pH s'est abaissé (P < 0,05 pour chacune). L'exposition au CO 2 a fait monter la TO 2 TC de 1,04 ± 0,67 à une valeur maximale de 1,49 ± 0,45 (P < 0,05 (34,9 ± 14,5 vs 11,4 ± 5,0 mmHg, P < 0,05 Objectif

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“…One such example surrounds the effects of hypercapnia on cell wounding. Hypercapnia has been demonstrated to protect against, and hypocapnia exacerbate, vascular barrier dysfunction in a number of injury models (Laffey et al 2000a;Laffey et al 2000b;Kavanagh 2005). Our group has confirmed the protective effect of hypercapnia as measured by reduced injury-related edema formation in alveolar epithelial cells (Doerr et al 2005).…”

Section: Consequence Of Deformation-induced Injurymentioning

confidence: 99%

Cell wounding and repair in ventilator injured lungs

Oeckler¹,

Hubmayr²

2008

Respiratory Physiology & Neurobiology

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Acute lung injury (ALI) is a common, frequently hospital acquired condition with a high morbidity and mortality. The stress associated with invasive mechanical ventilation represents a potentially harmful exposure, and attempts to minimize deforming stress through low tidal ventilation have proven efficacious. Lung cells are both sensors and transducers of deforming stress, and are frequently wounded in the setting of mechanical ventilation. Cell wounding may be one of the drivers of the innate immunologic and systemic inflammatory response associated with mechanical ventilation. These downstream effects of mechano-transduction have been referred to collectively as "Biotrauma". Our review will focus on cellular stress failure, that is cell wounding, and the mechanisms mediating subsequent plasma membrane repair, We hold that a better mechanistic understanding of cell plasticity, deformation associated remodeling and repair will reveal candidate approaches for lung protective interventions in mechanically ventilated patients. We will detail one such intervention, lung conditioning with hypertonic solutions as an example of ongoing research in this arena.

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Biological effects of hypercapnia

Cited by 47 publications

References 25 publications

Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat

Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat

L’hypercapnie augmente la tension en oxygène du tissu cérébral chez des rats anesthésiés

Cell wounding and repair in ventilator injured lungs

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