- Updated on August 3, 2021
These are references for the web page “Lung damage“.
Crit Care Med. 2003 Nov;31(11):2634-40.
Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation.
Laffey JG, Engelberts D, Duggan M, Veldhuizen R, Lewis JF, Kavanagh BP.
Lung Biology Program, The Research Institute and Department of Critical Care Medicine and Anesthesia, Hospital for Sick Children, Interdepartmental Division of Critical Care, University of Toronto, Ontario, Canada.
Abstract
OBJECTIVE: Deliberate elevation of PaCO2 (therapeutic hypercapnia) protects against lung injury induced by lung reperfusion and severe lung stretch. Conversely, hypocapnic alkalosis causes lung injury and worsens lung reperfusion injury. Alterations in lung surfactant may contribute to ventilator-associated lung injury. The potential for CO2 to contribute to the pathogenesis of ventilator-associated lung injury at clinically relevant tidal volumes is unknown. We hypothesized that: 1) hypocapnia would worsen ventilator-associated lung injury, 2) therapeutic hypercapnia would attenuate ventilator-associated lung injury; and 3) the mechanisms of impaired compliance would be via alteration of surfactant biochemistry. DESIGN: Randomized, prospective animal study. SETTING: Research laboratory of university-affiliated hospital. SUBJECTS: Anesthetized, male New Zealand Rabbits. INTERVENTIONS: All animals received the same ventilation strategy (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O; rate, 42 breaths/min) and were randomized to receive FiCO2 of 0.00, 0.05, or 0.12 to produce hypocapnia, normocapnia, and hypercapnia, respectively. MEASUREMENTS AND MAIN RESULTS: Alveolar-arterial oxygen gradient was significantly lower with therapeutic hypercapnia, and peak airway pressure was significantly higher with hypocapnic alkalosis. However, neither static lung compliance nor surfactant chemistry (total surfactant, aggregates, or composition) differed among the groups. CONCLUSIONS: At clinically relevant tidal volume, CO2 modulates key physiologic indices of lung injury, including alveolar-arterial oxygen gradient and airway pressure, indicating a potential role in the pathogenesis of ventilator-associated lung injury. These effects are surfactant independent.
Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):399-405.
Injurious effects of hypocapnic alkalosis in the isolated lung.
Laffey JG, Engelberts D, Kavanagh BP.
Department of Critical Care Medicine and The Lung Biology Program, The Research Institute, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
Abstract
Mechanical ventilation can worsen morbidity and mortality by causing ventilator-associated lung injury, especially where adverse ventilatory strategies are employed. Adverse strategies commonly involve hyperventilation, which frequently results in hypocapnia. Although hypocapnia is associated with significant lung alterations (e.g., bronchospasm, airway edema), the effects on alveolar-capillary permeability are unknown. We investigated whether hypocapnia could cause lung injury independent of altering ventilatory strategy. We hypothesized that hypocapnia would cause lung injury during prolonged ventilation, and would worsen injury following ischemia-reperfusion. We utilized the isolated buffer-perfused rabbit lung model. Pilot studies assessed a range of levels of hypocapnic alkalosis. Experimental preparations were randomized to control groups (FI(CO(2)) = 0.06) or groups with hypocapnia (FI(CO(2)) = 0.01). Following prolonged ventilation, pulmonary artery pressure, airway pressure, and lung weight were unchanged in the control group but were elevated in the group with hypocapnia; elevation in microvascular permeability was greater in the hypocapnia versus control groups. Injury following ischemia-reperfusion was significantly worse in the hypocapnia versus control groups. In a preliminary series, degree of lung injury was proportional to the degree of hypocapnic alkalosis. We conclude that in the current model (1) hypocapnic alkalosis is directly injurious to the lung and (2) hypocapnic alkalosis potentiates ischemia-reperfusion-induced acute lung injury.
Am Rev Respir Dis. 1992 Jan;145(1):80-4.
Airway hypocapnia increases microvascular leakage in the guinea pig trachea.
Reynolds AM, Zadow SP, Scicchitano R, McEvoy RD.
Department of Thoracic Medicine, Royal Adelaide Hospital, South Australia.
Abstract
We have previously shown that airway hypocapnia induced bronchoconstriction in the guinea pig lung by releasing tachykinins. To examine whether airway hypocapnia could also cause an increase in airway microvascular leakage, a tracheal segment was isolated in vivo in anesthetized guinea pigs and unidirectionally ventilated (200 ml/min) for 1 h with fully conditioned air (0% CO2) or isocapnic gas (5% CO2). The lungs were ventilated through a distally placed tracheal cannula. Microvascular leakage was produced by the injection of Evans blue (EB) and its extraction from the tracheal segment. EB extravasation was increased in tracheae exposed to 0% CO2 (52.3 +/- 2.0 micrograms/g wet tissue) compared with tracheae exposed to 5% CO2 (26.4 +/- 2.9 micrograms/g; p less than 0.05) and to tracheae from spontaneously breathing guinea pigs (25.2 +/- 2.3 micrograms/g; p less than 0.05). Groups of animals in which trachea were unidirectionally ventilated with 0% CO2 were then pretreated with a range of drugs in an attempt to determine the mediators responsible for the microvascular leakage with 0% CO2. Capsaicin and morphine pretreatment did not significantly alter 0% CO2-induced EB extravasation, and phosphoramidon prevented rather than increased extravasation, suggesting that tachykinins did not play a role. The hypocapnia-induced increase in microvascular leakage was, however, prevented by indomethacin pretreatment and significantly attenuated by dazmegrel, a thromboxane synthetase inhibitor. We conclude that airway hypocapnia causes microvascular leakage in the guinea pig trachea and that this effect is mediated by prostaglandins and/or thromboxane.
Surg Endosc. 2010 Feb 21. [Epub ahead of print]
Protective effect of carbon dioxide against bacterial peritonitis induced in rats.
Sorbello AA, Azevedo JL, Osaka JT, Damy S, Franua LM, Tolosa EC.
Departments of Surgical Gastroenterology and Experimental Surgery, San Paulo Hospital for State Civil Servants, San Paulo, Brazil, smcsorbello@uol.com.br.
Abstract
BACKGROUND: Carbon dioxide (CO(2)) has been used in the food industry as an antimicrobial agent. This study aimed to investigate whether CO(2) pneumoperitoneum might act similarly as an antimicrobial agent in the infected peritoneal cavity. METHODS: Peritonitis was induced in 58 rats by intraabdominal injection of an Escherichia coli inoculum (6 x 105 colony-forming units [CFU]/ml). Control rats were injected with saline solution. The rats were randomly divided into four groups: rat control (RC, n = 15), bacterial inoculation control (BIC, n = 10), bacterial inoculation and laparotomy (BIL, n = 17), and bacterial inoculation and CO(2) pneumoperitoneum (BIP, n = 16). The survival rates and histopathologic changes in the abdominal wall muscles, spleen, liver, intestines, and omentum were evaluated, and the samples were classified as “preserved” or “inflamed” (acute inflammation or tissue regeneration). RESULTS: The survival rates for the four groups were as follows: RC (100%), BIP (75%), BIL (53%), and BIC (30%). With regard to survival rates, statistically significant differences were observed between the following groups: RC and BIC (p = 0.0009), RC and BIL (p = 0.0045), BIP and BIC (p = 0.0332), and RC and BIP (p = 0.0470). No significant differences regarding survival rates were observed between the BIL and BIC groups or between the BIP and BIL groups. With regard to the number of inflamed samples per group, a statistically significant difference was observed between the BIC and RC groups and the BIL and RC groups (p = 0.05). CONCLUSION: Carbon dioxide pneumoperitoneum has a protective effect against bacterial peritonitis induced in rats.
Anesthesiology. 1993 Jan;78(1):91-9.
Hypocapnia worsens arterial blood oxygenation and increases VA/Q heterogeneity in canine pulmonary edema.
Domino KB, Lu Y, Eisenstein BL, Hlastala MP.
University of Washington Medical School, Seattle.
Abstract
BACKGROUND: Hyperventilation frequently is employed to reduce carbon dioxide partial pressure in patients in the operating room and intensive care unit. However the effect of hypocapnia on oxygenation is complex and may result in worsening in patients with preexisting intrapulmonary shunt. To better define the interplay between hypocapnia and oxygenation, the effects of hypocapnia and hypercapnia on the matching of ventilation (VA) and perfusion (Q) were studied in dogs with oleic acid-induced pulmonary edema, using the multiple inert gas elimination technique. METHODS: Eight pentobarbital-anesthetized, closed-chested dogs were administered 0.06 ml/kg of oleic acid at least 150 min prior to study. Ventilation was set with an FIO2 of 0.90, a tidal volume of 20 ml/kg, and a respiratory rate of 35 breaths/min. The arterial carbon dioxide tension (PaCO2) was varied in a randomized order to three levels (26, 38, and 50 mmHg) by altering the amount of CO2 in the inspired gas mixture. Gas exchange was assessed by true shunt, dead space, the log standard deviation of the perfusion (log SDQ) and the ventilation (log SDV) distributions, and the tracer inert gas arterial-alveolar difference ([a-A]D) area. RESULTS: Cardiac output (4.1 +/- 0.4 L/min), mean pulmonary artery pressure (25 +/- 1 mmHg), inert gas shunt (22 +/- 3%), and dead space (38 +/- 4%) during normocapnia were not different from that during hypocapnia and hypercapnia. Hypocapnia increased (P < .05) the alveolar-arterial oxygen tension difference (P[A-a]O2) and decreased (P < .05) the arterial blood oxygen tension (PaO2, 181 +/- 33 mmHg vs. 221 +/- 35 mmHg with normocapnia). P[A-a]O2 and PaO2 were unaffected by hypercapnia. During hypocapnia, VA/Q inequality increased, demonstrated by an increase (P < .05) in log SDQ (1.60 +/- 0.15 vs. 1.35 +/- 0.19 with normocapnia) and in the [a-A]D area (0.63 +/- 0.09 vs. 0.50 +/- 0.09 with normocapnia) indexes of VA/Q heterogeneity. During hypercapnia, the [a-A]D area (0.63 +/- 0.11) and log SDV (1.13 +/- 0.10 compared to 0.97 +/- 0.12 with normocapnia) also were increased (P < .05). With hypocapnia, there was a small but insignificant increase in blood flow to shunt and low VA/Q areas (29 +/- 4% compared to 26 +/- 4% with normocapnia). In the presence of a high FIO2, this small increase in shunt and low VA/Q may result in a significant decrease in PaO2. CONCLUSIONS: Both hypocapnia and hypercapnia were associated with an increased VA/Q inequality. However, PaO2 decreased and P[A-a]O2 increased with only hypocapnia. These results suggest that hyperventilation to reduce PaCO2 may be detrimental to arterial PO2 in some patients with lung disease.
