Liquid breathing

Last updated
Liquid breathing
Perflubron and gentamicin molecules.png
Computer-generated model of perflubron and gentamicin molecules in liquid suspension for pulmonary administration
MeSH D021061

Liquid breathing is a form of respiration in which a normally air-breathing organism breathes an oxygen-rich liquid (such as a perfluorocarbon), rather than breathing air, by selecting a liquid that can hold a large amount of oxygen and is capable of CO2 gas exchange. [1]

Contents

This requires certain physical properties such as respiratory gas solubility, density, viscosity, vapor pressure, and lipid solubility which some perfluorochemicals (PFCs) have. [2] Thus, it is critical to choose the appropriate PFC for a specific biomedical application, such as liquid ventilation, drug delivery or blood substitutes. The physical properties of PFC liquids vary substantially; however, the one common property is their high solubility for respiratory gases. In fact, these liquids carry more oxygen and carbon dioxide than blood. [3]

In theory, liquid breathing could assist in the treatment of patients with severe pulmonary or cardiac trauma, especially in pediatric cases.[ how? ] Liquid breathing has also been proposed for use in deep diving [4] [5] [6] and space travel. [7] [8] Despite some recent advances in liquid ventilation, a standard mode of application has not yet been established.

Approaches

Physicochemical properties (37 °C at 1 atm) of 18 perfluorochemical liquids used for biomedical applications. This table characterizes the most significant physical properties related to systemic physiology and their range of properties.
Gas solubility
Oxygen33–66 mL / 100 mL PFC
Carbon dioxide140–166 mL / 100 mL PFC
Vapor pressure0.2–400 torr
Density1.58–2.0 g/mL
Viscosity0.8–8.0 cSt
FC-75 Molecule.png
Perflubron Molecule.png
Perfluorodecalin molecule.png
Computer models of three perfluorochemical molecules used for biomedical applications and for liquid ventilation studies: a) FC-75, b) perflubron, and c) perfluorodecalin.

Because liquid breathing is still a highly experimental technique, there are several proposed approaches.

Total liquid ventilation

Although total liquid ventilation (TLV) with completely liquid-filled lungs can be beneficial, [9] the complex liquid-filled tube system required is a disadvantage compared to gas ventilation—the system must incorporate a membrane oxygenator, heater, and pumps to deliver to, and remove from the lungs tidal volume aliquots of conditioned perfluorocarbon (PFC). One research group led by Thomas H. Shaffer has maintained that with the use of microprocessors and new technology, it is possible to maintain better control of respiratory variables such as liquid functional residual capacity and tidal volume during TLV than with gas ventilation. [2] [10] [11] [12] Consequently, the total liquid ventilation necessitates a dedicated liquid ventilator similar to a medical ventilator except that it uses a breathable liquid. Many prototypes are used for animal experimentation, but experts recommend continued development of a liquid ventilator toward clinical applications. [13] Specific preclinical liquid ventilator (Inolivent) is currently under joint development in Canada and France. [14] The main application of this liquid ventilator is the ultra-fast induction of therapeutic hypothermia after cardiac arrest. This has been demonstrated to be more protective than slower cooling method after experimental cardiac arrest. [15]

Partial liquid ventilation

In contrast, partial liquid ventilation (PLV) is a technique in which a PFC is instilled into the lung to a volume approximating functional residual capacity (approximately 40% of total lung capacity). Conventional mechanical ventilation delivers tidal volume breaths on top of it. This mode of liquid ventilation currently seems technologically more feasible than total liquid ventilation, because PLV could utilise technology currently in place in many neonatal intensive-care units (NICU) worldwide.

The influence of PLV on oxygenation, carbon dioxide removal and lung mechanics has been investigated in several animal studies using different models of lung injury. [16] Clinical applications of PLV have been reported in patients with acute respiratory distress syndrome (ARDS), meconium aspiration syndrome, congenital diaphragmatic hernia and respiratory distress syndrome (RDS) of neonates. In order to correctly and effectively conduct PLV, it is essential to

  1. properly dose a patient to a specific lung volume (10–15 ml/kg) to recruit alveolar volume
  2. redose the lung with PFC liquid (1–2 ml/kg/h) to oppose PFC evaporation from the lung.

If PFC liquid is not maintained in the lung, PLV can not effectively protect the lung from biophysical forces associated with the gas ventilator.

New application modes for PFC have been developed. [17]

Partial liquid ventilation (PLV) involves filling the lungs with a liquid. This liquid is a perfluorocarbon such as perflubron (brand name Liquivent). The liquid has some unique properties. It has a very low surface tension, similar to the surfactant substances produced in the lungs to prevent the alveoli from collapsing and sticking together during exhalation. It also has a high density, oxygen readily diffuses through it, and it may have some anti-inflammatory properties. In PLV, the lungs are filled with the liquid, the patient is then ventilated with a conventional ventilator using a protective lung ventilation strategy. The hope is that the liquid will help the transport of oxygen to parts of the lung that are flooded and filled with debris, help remove this debris and open up more alveoli improving lung function. The study of PLV involves comparison to protocolized ventilator strategy designed to minimize lung damage. [18] [19]

PFC vapor

Vaporization of perfluorohexane with two anesthetic vaporizers calibrated for perfluorohexane has been shown to improve gas exchange in oleic acid-induced lung injury in sheep. [20]

Predominantly PFCs with high vapor pressure are suitable for vaporization.

Aerosol-PFC

With aerosolized perfluorooctane, significant improvement of oxygenation and pulmonary mechanics was shown in adult sheep with oleic acid-induced lung injury.

In surfactant-depleted piglets, persistent improvement of gas exchange and lung mechanics was demonstrated with Aerosol-PFC. [21] The aerosol device is of decisive importance for the efficacy of PFC aerosolization, as aerosolization of PF5080 (a less purified FC77) has been shown to be ineffective using a different aerosol device in surfactant-depleted rabbits. Partial liquid ventilation and Aerosol-PFC reduced pulmonary inflammatory response. [22]

Human usage

Medical treatment

The most promising area for the use of liquid ventilation is in the field of pediatric medicine. [23] [24] [25] The first medical use of liquid breathing was treatment of premature babies [26] [27] [28] [29] and adults with acute respiratory distress syndrome (ARDS) in the 1990s. Liquid breathing was used in clinical trials after the development by Alliance Pharmaceuticals of the fluorochemical perfluorooctyl bromide, or perflubron for short. Current methods of positive-pressure ventilation can contribute to the development of lung disease in pre-term neonates, leading to diseases such as bronchopulmonary dysplasia. Liquid ventilation removes many of the high pressure gradients responsible for this damage. Furthermore, perfluorocarbons have been demonstrated to reduce lung inflammation, [30] [31] [32] improve ventilation-perfusion mismatch and to provide a novel route for the pulmonary administration of drugs. [30] [33] [34]

In order to explore drug delivery techniques that would be useful for both partial and total liquid ventilation, more recent studies have focused on PFC drug delivery using a nanocrystal suspension. The first image is a computer model of a PFC liquid (perflubron) combined with gentamicin molecules.

The second image shows experimental results comparing both plasma and tissue levels of gentamicin after an intratracheal (IT) and intravenous (IV) dose of 5 mg/kg in a newborn lamb during gas ventilation. Note that the plasma levels of the IV dose greatly exceed the levels of the IT dose over the 4 hour study period; whereas, the lung tissue levels of gentamicin when delivered by an intratracheal (IT) suspension, uniformly exceed the intravenous (IV) delivery approach after 4 hours. Thus, the IT approach allows more effective delivery of the drug to the target organ while maintaining a safer level systemically. Both images represent the in-vivo time course over 4 hours. Numerous studies have now demonstrated the effectiveness of PFC liquids as a delivery vehicle to the lungs. [35] [36] [37] [38] [34] [39] [33] [40] [30] [41]

Comparison of IT and IV administration of gentamicin. Gentamicin levels.png
Comparison of IT and IV administration of gentamicin.

Clinical trials with premature infants and adults have been conducted. [42] Since the safety of the procedure and the effectiveness were apparent from an early stage, the US Food and Drug Administration (FDA) gave the product "fast track" status (meaning an accelerated review of the product, designed to get it to the public as quickly as is safely possible) due to its life-saving potential. Clinical trials showed that using perflubron with ordinary ventilators improved outcomes as much as using high frequency oscillating ventilation (HFOV). But because perflubron was not better than HFOV, the FDA did not approve perflubron, and Alliance is no longer pursuing the partial liquid ventilation application. Whether perflubron would improve outcomes when used with HFOV or has fewer long-term consequences than HFOV remains an open question.

In 1996 Mike Darwin and Steven B. Harris proposed using cold liquid ventilation with perfluorocarbon to quickly lower the body temperature of victims of cardiac arrest and other brain trauma to allow the brain to better recover. [43] The technology came to be called gas/liquid ventilation (GLV), and was shown able to achieve a cooling rate of 0.5 °C per minute in large animals. [44] It has not yet been tried in humans.

Most recently, hypothermic brain protection has been associated with rapid brain cooling. In this regard, a new therapeutic approach is the use of intranasal perfluorochemical spray for preferential brain cooling. [45] The nasopharyngeal (NP) approach is unique for brain cooling due to anatomic proximity to the cerebral circulation and arteries. Based on preclinical studies in adult sheep, it was shown that independent of region, brain cooling was faster during NP-perfluorochemical versus conventional whole body cooling with cooling blankets. To date, there have been four human studies including a completed randomized intra-arrest study (200 patients). [46] [47] Results clearly demonstrated that prehospital intra-arrest transnasal cooling is safe, feasible and is associated with an improvement in cooling time.

Proposed uses

Diving

Gas pressure increases with depth, rising 1 bar (14.5 psi (100 kPa)) every 10 meters to over 1,000 bar at the bottom of the Mariana Trench. Diving becomes more dangerous as depth increases, and deep diving presents many hazards. All surface-breathing animals are subject to decompression sickness, including aquatic mammals [48] and free-diving humans. Breathing at depth can cause nitrogen narcosis and oxygen toxicity. Holding the breath while ascending after breathing at depth can cause air embolisms, burst lung, and collapsed lung.

Special breathing gas mixes such as trimix or heliox reduce the risk of nitrogen narcosis but do not eliminate it. Heliox further eliminates the risk of nitrogen narcosis but introduces the risk of helium tremors below about 500 feet (150 m). Atmospheric diving suits maintain body and breathing pressure at 1 bar, eliminating most of the hazards of descending, ascending, and breathing at depth. However, the rigid suits are bulky, clumsy, and very expensive.

Liquid breathing offers a third option, [4] [49] promising the mobility available with flexible dive suits and the reduced risks of rigid suits. With liquid in the lungs, the pressure within the diver's lungs could accommodate changes in the pressure of the surrounding water without the huge partial pressure gas exposures required when the lungs are filled with gas. Liquid breathing would not result in the saturation of body tissues with high pressure nitrogen or helium that occurs with the use of non-liquids, thus would reduce or remove the need for slow decompression.

A significant problem, however, arises from the high viscosity of the liquid and the corresponding reduction in its ability to remove CO2. [4] [50] All uses of liquid breathing for diving must involve total liquid ventilation (see above). Total liquid ventilation, however, has difficulty moving enough liquid to carry away CO2, because no matter how great the total pressure is, the amount of partial CO2 gas pressure available to dissolve CO2 into the breathing liquid can never be much more than the pressure at which CO2 exists in the blood (about 40 mm of mercury (Torr)). [50]

At these pressures, most fluorocarbon liquids require about 70 mL/kg minute-ventilation volumes of liquid (about 5 L/min for a 70 kg adult) to remove enough CO2 for normal resting metabolism. [51] This is a great deal of fluid to move, particularly as liquids are more viscous and denser than gases, (for example water is about 850 times the density of air [52] ). Any increase in the diver's metabolic activity also increases CO2 production and the breathing rate, which is already at the limits of realistic flow rates in liquid breathing. [4] [53] [54] It seems unlikely that a person would move 10 liters/min of fluorocarbon liquid without assistance from a mechanical ventilator, so "free breathing" may be unlikely. However, it has been suggested that a liquid breathing system could be combined with a CO2 scrubber connected to the diver's blood supply; a US patent has been filed for such a method. [55] [56]

Space travel

Liquid immersion provides a way to reduce the physical stress of G forces. Forces applied to fluids are distributed as omnidirectional pressures. Because liquids cannot be practically compressed, they do not change density under high acceleration such as performed in aerial maneuvers or space travel. A person immersed in liquid of the same density as tissue has acceleration forces distributed around the body, rather than applied at a single point such as a seat or harness straps. This principle is used in a new type of G-suit called the Libelle G-suit, which allows aircraft pilots to remain conscious and functioning at more than 10g acceleration by surrounding them with water in a rigid suit. [57]

Acceleration protection by liquid immersion is limited by the differential density of body tissues and immersion fluid, limiting the utility of this method to about 15g to 20g. [58] Extending acceleration protection beyond 20g requires filling the lungs with fluid of density similar to water. An astronaut totally immersed in liquid, with liquid inside all body cavities, will feel little effect from extreme G forces because the forces on a liquid are distributed equally, and in all directions simultaneously. Effects will still be felt because of density differences between different body tissues, so an upper acceleration limit still exists. However, it can likely be higher than hundreds of G. [59]

Liquid breathing for acceleration protection may never be practical because of the difficulty of finding a suitable breathing medium of similar density to water that is compatible with lung tissue. Perfluorocarbon fluids are twice as dense as water, hence unsuitable for this application. [3]

Examples in fiction

Literary works

Films and television

Video games

See also

Related Research Articles

<span class="mw-page-title-main">Hypoxia (medicine)</span> Medical condition of lack of oxygen in the tissues

Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.

<span class="mw-page-title-main">Respiratory system</span> Biological system in animals and plants for gas exchange

The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies greatly, depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals, the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs; in mammals and reptiles, these are called alveoli, and in birds, they are known as atria. These microscopic air sacs have a very rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi. These enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds, the bronchioles are termed parabronchi. It is the bronchioles, or parabronchi that generally open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration.

<span class="mw-page-title-main">Respiratory failure</span> Inadequate gas exchange by the respiratory system

Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type 1 or Type 2, based on whether there is a high carbon dioxide level, and can be acute or chronic. In clinical trials, the definition of respiratory failure usually includes increased respiratory rate, abnormal blood gases, and evidence of increased work of breathing. Respiratory failure causes an altered state of consciousness due to ischemia in the brain.

Apnea, BrE: apnoea, is the temporary cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are, there may or may not be a flow of gas between the lungs and the environment. If there is sufficient flow, gas exchange within the lungs and cellular respiration would not be severely affected. Voluntarily doing this is called holding one's breath. Apnea may first be diagnosed in childhood, and it is recommended to consult an ENT specialist, allergist or sleep physician to discuss symptoms when noticed; malformation and/or malfunctioning of the upper airways may be observed by an orthodontist.

<span class="mw-page-title-main">Mechanical ventilation</span> Method to mechanically assist or replace spontaneous breathing

Mechanical ventilation or assisted ventilation is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, with the main goal of helping the delivery of oxygen and removal of carbon dioxide. Mechanical ventilation is used for many reasons, including to protect the airway due to mechanical or neurologic cause, to ensure adequate oxygenation, or to remove excess carbon dioxide from the lungs. Various healthcare providers are involved with the use of mechanical ventilation and people who require ventilators are typically monitored in an intensive care unit.

<span class="mw-page-title-main">Acute respiratory distress syndrome</span> Human disease

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased quality of life is common.

<span class="mw-page-title-main">Hypercapnia</span> Abnormally high tissue carbon dioxide levels

Hypercapnia (from the Greek hyper = "above" or "too much" and kapnos = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the body's metabolism and is normally expelled through the lungs. Carbon dioxide may accumulate in any condition that causes hypoventilation, a reduction of alveolar ventilation (the clearance of air from the small sacs of the lung where gas exchange takes place) as well as resulting from inhalation of CO2. Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO2, leads to respiratory acidosis. Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as "metabolic compensation".

<span class="mw-page-title-main">Oxygen therapy</span> Use of oxygen as a medical treatment

Oxygen therapy, also referred to as supplemental oxygen, is the use of oxygen as medical treatment. Supplemental oxygen can also refer to the use of oxygen enriched air at altitude. Acute indications for therapy include hypoxemia, carbon monoxide toxicity and cluster headache. It may also be prophylactically given to maintain blood oxygen levels during the induction of anesthesia. Oxygen therapy is often useful in chronic hypoxemia caused by conditions such as severe COPD or cystic fibrosis. Oxygen can be delivered via nasal cannula, face mask, or endotracheal intubation at normal atmospheric pressure, or in a hyperbaric chamber. It can also be given through bypassing the airway, such as in ECMO therapy.

<span class="mw-page-title-main">Infant respiratory distress syndrome</span> Human disease affecting newborns

Infant respiratory distress syndrome (IRDS), also called respiratory distress syndrome of newborn, or increasingly surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfactant production and structural immaturity in the lungs. It can also be a consequence of neonatal infection and can result from a genetic problem with the production of surfactant-associated proteins.

<span class="mw-page-title-main">Hypoxemia</span> Abnormally low level of oxygen in the blood

Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia has many causes, and often causes hypoxia as the blood is not supplying enough oxygen to the tissues of the body.

<span class="mw-page-title-main">Alveolar lung disease</span> Medical condition

Alveolar lung diseases, are a group of diseases that mainly affect the alveoli of the lungs.

<span class="mw-page-title-main">Perfluorohexane</span> Chemical compound

Perfluorohexane, or tetradecafluorohexane, is a fluorocarbon. It is a derivative of hexane in which all the hydrogen atoms are replaced by fluorine atoms. It is used in one formulation of the electronic cooling liquid/insulator Fluorinert for low-temperature applications due to its low boiling point of 56 °C and freezing point of −90 °C. It is odorless and colorless. Unlike typical hydrocarbons, the structure features a helical carbon backbone.

A pulmonary shunt is the passage of deoxygenated blood from the right side of the heart to the left without participation in gas exchange in the pulmonary capillaries. It is a pathological condition that results when the alveoli of parts of the lungs are perfused with blood as normal, but ventilation fails to supply the perfused region. In other words, the ventilation/perfusion ratio of those areas is zero.

The Alveolar–arterial gradient, is a measure of the difference between the alveolar concentration (A) of oxygen and the arterial (a) concentration of oxygen. It is a useful parameter for narrowing the differential diagnosis of hypoxemia.

<span class="mw-page-title-main">Pulmonary contusion</span> Internal bruise of the lungs

A pulmonary contusion, also known as lung contusion, is a bruise of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels (hypoxia). Unlike pulmonary laceration, another type of lung injury, pulmonary contusion does not involve a cut or tear of the lung tissue.

<span class="mw-page-title-main">Liquid ventilator</span> Medical device

A liquid ventilator is similar to a medical ventilator except that it should be able to ensure reliable total liquid ventilation with a breatheable liquid ·. Liquid ventilators are prototypes that may have been used for animal experimentations but experts recommend continued development of a liquid ventilator toward clinical applications.

<span class="mw-page-title-main">Heated humidified high-flow therapy</span> Respiratory support method

Heated humidified high-flow therapy, often simply called high flow therapy, is a type of respiratory support that delivers a flow of medical gas to a patient of up to 60 liters per minute and 100% oxygen through a large bore or high flow nasal cannula. Primarily studied in neonates, it has also been found effective in some adults to treat hypoxemia and work of breathing issues. The key components of it are a gas blender, heated humidifier, heated circuit, and cannula.

Modes of mechanical ventilation are one of the most important aspects of the usage of mechanical ventilation. The mode refers to the method of inspiratory support. In general, mode selection is based on clinician familiarity and institutional preferences, since there is a paucity of evidence indicating that the mode affects clinical outcome. The most frequently used forms of volume-limited mechanical ventilation are intermittent mandatory ventilation (IMV) and continuous mandatory ventilation (CMV). There have been substantial changes in the nomenclature of mechanical ventilation over the years, but more recently it has become standardized by many respirology and pulmonology groups. Writing a mode is most proper in all capital letters with a dash between the control variable and the strategy.

<span class="mw-page-title-main">Pathophysiology of acute respiratory distress syndrome</span>

The pathophysiology of acute respiratory distress syndrome involves fluid accumulation in the lungs not explained by heart failure. It is typically provoked by an acute injury to the lungs that results in flooding of the lungs' microscopic air sacs responsible for the exchange of gases such as oxygen and carbon dioxide with capillaries in the lungs. Additional common findings in ARDS include partial collapse of the lungs (atelectasis) and low levels of oxygen in the blood (hypoxemia). The clinical syndrome is associated with pathological findings including pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of chemical signals and other inflammatory mediators secreted by local epithelial and endothelial cells.

<span class="mw-page-title-main">Ventilation–perfusion coupling</span> Relationship between respiratory and cardiovascular processes

Ventilation-perfusion coupling is the relationship between ventilation and perfusion processes, which take place in the respiratory system and the cardiovascular system. Ventilation is the movement of gas during breathing, and perfusion is the process of pulmonary blood circulation, which delivers oxygen to body tissues. Anatomically, the lung structure, alveolar organization, and alveolar capillaries contribute to the physiological mechanism of ventilation and perfusion. Ventilation-perfusion coupling maintains a constant ventilation/perfusion ratio near 0.8 on average, while the regional variation exists within the lungs due to gravity. When the ratio gets above or below 0.8, it is considered abnormal ventilation-perfusion coupling, also known as a ventilation–perfusion mismatch. Lung diseases, cardiac shunts, and smoking can cause a ventilation-perfusion mismatch that results in significant symptoms and diseases, which can be treated through treatments like bronchodilators and oxygen therapy.

References

  1. ↑ GAEDEKE NORMS, M., RN, MSN, CCRN, CS, et al. Liquid Ventilation: It's Not Science Fiction Anymore. AACN Clin Issues Crit Care Nurs. 1994;5(3):246-254. Cited in: Your Journals@Ovid Full Text at http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=yrovftb&NEWS=N&AN=00002245-199408000-00004 .
  2. 1 2 Shaffer, Thomas H.; Wolfson, Marla R.; Clark, Leland C. (Oct 1992). "Liquid ventilation". Pediatric Pulmonology. 14 (2): 102–109. doi:10.1002/ppul.1950140208. PMID   1437347. S2CID   222167378.
  3. 1 2 Gabriel, Jerome L.; Miller, T. F.; Wolfson, Marla R.; Shaffer, Thomas H. (Nov 1996). "Quantitative Structure-Activity Relationships of Perfluorinated Hetero-Hydrocarbons as Potential Respiratory Media: Application to Oxygen Solubility, Partition Coefficient, Viscosity, Vapor Pressure, and Density". ASAIO Journal. 42 (6): 968–973. doi:10.1097/00002480-199642060-00009. ISSN   1058-2916. PMID   8959271. S2CID   31161098.
  4. 1 2 3 4 Kylstra JA (1977). The Feasibility of Liquid Breathing in Man. Vol. Report to the US Office of Naval Research. Durham, NC: Duke University. Archived from the original on 2008-07-07. Retrieved 2008-05-05.{{cite book}}: CS1 maint: unfit URL (link)
  5. ↑ "menfish". Archived from the original on 2008-05-16. Retrieved 2008-05-17.
  6. ↑ Featured on the ABC television program That's Incredible, including a demonstration of a mouse surviving a prolonged dunking in perfluorocarbon.
  7. ↑ "Liquid Breathing - Medical uses". Archived from the original on 2010-04-15. Retrieved 2008-05-17.
  8. ↑ Featured on the ABC television program That's Incredible. Cathy Lee Crosby describing diving and spaceflight applications. Voiceover with stock video.
  9. ↑ Wolfson, Marla R.; Hirschl, Ronald B.; Jackson, J Craig; Gauvin, France; Foley, David S.; Lamm, Wayne J. E.; Gaughan, John; Shaffer, Thomas H. (May 2008). "Multicenter Comparative Study of Conventional Mechanical Gas Ventilation to Tidal Liquid Ventilation in Oleic Acid Injured Sheep". ASAIO Journal. 54 (3): 256–269. doi: 10.1097/MAT.0b013e318168fef0 . ISSN   1058-2916. PMID   18496275. S2CID   2647244.
  10. ↑ Cox CA, Stavis RL. Wolfson MR, Shaffer TH; Stavis; Wolfson; Shaffer (2003). "Long-term tidal liquid ventilation in premature lambs: Physiologic, biochemical and histological correlates". Biol. Neonate. 84 (3): 232–242. doi:10.1159/000072307. PMID   14504447. S2CID   46143608.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Libros, R.; Philips, C. M.; Wolfson, M. R.; Shaffer, T. H. (Sep 2000). "A perfluorochemical loss/restoration (L/R) system for tidal liquid ventilation". Biomedical Instrumentation & Technology. 34 (5): 351–360. ISSN   0899-8205. PMID   11098391.
  12. ↑ Heckman, J. L.; Hoffman, J.; Shaffer, T. H.; Wolfson, M. R. (May 1999). "Software for real-time control of a tidal liquid ventilator". Biomedical Instrumentation & Technology. 33 (3): 268–276. ISSN   0899-8205. PMID   10360217.
  13. ↑ Costantino, ML; Micheau, P; Shaffer, TH; Tredici, S; et al. (2009). "Clinical design functions: Round table discussions on bioengineering of liquid ventilators". ASAIO J. 55 (3): 206–8. doi: 10.1097/MAT.0b013e318199c167 . PMID   19282746.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  14. ↑ "Inolivent".
  15. ↑ Kohlhauer, Matthias; Lidouren, Fanny; Remy-Jouet, Isabelle; Mongardon, Nicolas; Adam, Clovis; Bruneval, Patrick; Hocini, Hakim; Levy, Yves; Blengio, Fabiola (Oct 2015). "Hypothermic Total Liquid Ventilation Is Highly Protective Through Cerebral Hemodynamic Preservation and Sepsis-Like Mitigation After Asphyxial Cardiac Arrest*". Critical Care Medicine. 43 (10): e420–e430. doi:10.1097/CCM.0000000000001160. ISSN   0090-3493. PMID   26110489. S2CID   10245455.
  16. ↑ Clark, L. C.; Gollan, F. (1966-06-24). "Survival of Mammals Breathing Organic Liquids Equilibrated with Oxygen at Atmospheric Pressure". Science. 152 (3730): 1755–1756. Bibcode:1966Sci...152.1755C. doi:10.1126/science.152.3730.1755. ISSN   0036-8075. PMID   5938414. S2CID   12998179.
  17. ↑ Hlastala, Michael P.; Souders, Jennifer E. (Jul 2001). "Perfluorocarbon Enhanced Gas Exchange: The Easy Way". American Journal of Respiratory and Critical Care Medicine. 164 (1): 1–2. doi:10.1164/ajrccm.164.1.2104021a. ISSN   1073-449X. PMID   11435228. A significant positive step was the use of PFC-associated gas exchange, now termed partial liquid ventilation (PLV).
  18. ↑ Hirschl, Ronald B.; Pranikoff, T; Wise, C; Overbeck, MC; et al. (1996-02-07). "Initial Experience With Partial Liquid Ventilation in Adult Patients With the Acute Respiratory Distress Syndrome". JAMA: The Journal of the American Medical Association. 275 (5): 383–389. doi:10.1001/jama.1996.03530290053037. ISSN   0098-7484. PMID   8569018.
  19. ↑ Verbrugge, S.J.C.; Lachmann, B. (1997-09-01). "Partial liquid ventilation". European Respiratory Journal. 10 (9): 1937–1939. doi: 10.1183/09031936.97.10091937 . PMID   9311481.[ permanent dead link ] (editorial)
  20. ↑ Bleyl, Jorg U.; Ragaller, Maximilian; Tscho, Uwe; Regner, Mike; Kanzow, Maria; Hubler, Matthias; Rasche, Stefan; Albrecht, Michael (Aug 1999). "Vaporized Perfluorocarbon Improves Oxygenation and Pulmonary Function in an Ovine Model of Acute Respiratory Distress Syndrome". Anesthesiology. 91 (2): 461–469. doi: 10.1097/00000542-199908000-00021 . ISSN   0003-3022. PMID   10443610. Vaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid-induced lung injury.
  21. ↑ Kandler, Michael A.; von der HARDT, Katharina; Schoof, Ellen; Dötsch, Jörg; Rascher, Wolfgang (Jul 2001). "Persistent Improvement of Gas Exchange and Lung Mechanics by Aerosolized Perfluorocarbon". American Journal of Respiratory and Critical Care Medicine. 164 (1): 31–35. doi:10.1164/ajrccm.164.1.2010049. ISSN   1073-449X. PMID   11435235. Aerosolized perfluorocarbon improved pulmonary gas exchange and lung mechanics as effectively as PLV did in surfactant-depleted piglets, and the improvement was sustained longer.
  22. ↑ Von Der Hardt, Katharina; Schoof, Ellen; Kandler, Michael A; Dötsch, Jörg; Rascher, Wolfgang (Feb 2002). "Aerosolized Perfluorocarbon Suppresses Early Pulmonary Inflammatory Response in a Surfactant-Depleted Piglet Model". Pediatric Research. 51 (2): 177–182. doi: 10.1203/00006450-200202000-00009 . ISSN   0031-3998. PMID   11809911. In a surfactant-depleted piglet model, aerosol therapy with perfluorocarbon but not LV-PLV reduces the initial pulmonary inflammatory reaction at least as potently as PLV at FRC volume.
  23. ↑ Wolfson, Marla R.; Kechner, Nancy E.; Roache, Robert F.; Dechadarevian, Jean-Pierre; et al. (Feb 1998). "Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency". Journal of Applied Physiology. 84 (2): 624–640. doi:10.1152/jappl.1998.84.2.624. ISSN   8750-7587. PMID   9475875. S2CID   25351115.
  24. ↑ Stavis, Robert L; Wolfson, Marla R; Cox, Cynthia; Kechner, Nancy; Shaffer, Thomas H (Jan 1998). "Physiologic, Biochemical, and Histologic Correlates Associated with Tidal Liquid Ventilation". Pediatric Research. 43 (1): 132–138. doi: 10.1203/00006450-199801000-00020 . ISSN   0031-3998. PMID   9432124.
  25. ↑ Wolfson, Marla R.; Shaffer, Thomas H. (Jun 2005). "Pulmonary applications of perfluorochemical liquids: Ventilation and beyond". Paediatric Respiratory Reviews. 6 (2): 117–127. doi:10.1016/j.prrv.2005.03.010. PMID   15911457.
  26. ↑ Greenspan, JS; Wolfson, MR; Rubenstein, SD; Shaffer, TH (1989). "Liquid ventilation of preterm baby". The Lancet . 2 (8671): 1095. doi:10.1016/S0140-6736(89)91101-X. PMID   2572810. S2CID   29173957.
  27. ↑ Greenspan, Jay S.; Wolfson, Marla R.; Rubenstein, S. David; Shaffer, Thomas H. (Jul 1990). "Liquid ventilation of human preterm neonates". The Journal of Pediatrics. 117 (1): 106–111. doi:10.1016/S0022-3476(05)82457-6. PMID   2115078.
  28. ↑ Leach, CL; Greenspan, JS; Rubenstein, SD; Shaffer, TH; et al. (September 1996). "Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome. The LiquiVent Study Group". The New England Journal of Medicine . 335 (11): 761–7. doi: 10.1056/NEJM199609123351101 . PMID   8778584.
  29. ↑ Greenspan, J. S.; Fox, W. W.; Rubenstein, S. D.; Wolfson, M. R.; Spinner, S. S.; Shaffer, T. H.; Philadelphia Liquid Ventilation Consortium (1997-01-01). "Partial Liquid Ventilation in Critically Ill Infants Receiving Extracorporeal Life Support". Pediatrics. 99 (1): E2. doi:10.1542/peds.99.1.e2. ISSN   0031-4005. PMID   9096170.
  30. 1 2 3 Brunelli, Luca; Hamilton, Eric; Davis, Jonathan M; Koo, Hshi-Chi; et al. (Jul 2006). "Perfluorochemical Liquids Enhance Delivery of Superoxide Dismutase to the Lungs of Juvenile Rabbits". Pediatric Research. 60 (1): 65–70. doi: 10.1203/01.pdr.0000219392.73509.70 . ISSN   0031-3998. PMID   16690961.
  31. ↑ Nakstad, Britt; Wolfson, Marla R.; Shaffer, Thomas H.; Kähler, Hanne; Lindemann, Rolf; Fugelseth, Drude; Lyberg, Torstein (Sep 2001). "Perfluorochemical liquids modulate cell-mediated inflammatory responses". Critical Care Medicine. 29 (9): 1731–1737. doi:10.1097/00003246-200109000-00013. ISSN   0090-3493. PMID   11546973. S2CID   20704132.
  32. ↑ Ramesh Babu, Polani B.; Chidekel, Aaron; Shaffer, Thomas H. (Mar 2005). "Hyperoxia-induced changes in human airway epithelial cells: The protective effect of perflubron". Pediatric Critical Care Medicine. 6 (2): 188–194. doi:10.1097/01.PCC.0000154944.67042.4F. ISSN   1529-7535. PMID   15730607. S2CID   21857004.
  33. 1 2 Cox, Cynthia A.; Cullen, Aaron B.; Wolfson, Marla R.; Shaffer, Thomas H. (Aug 2001). "Intratracheal administration of perfluorochemical-gentamicin suspension: A comparison to intravenous administration in normal and injured lungs". Pediatric Pulmonology. 32 (2): 142–151. doi:10.1002/ppul.1100. ISSN   8755-6863. PMID   11477731. S2CID   33298231.
  34. 1 2 Fox, W. W.; Weis, C. M.; Cox, C.; Farina, C.; et al. (1997-11-01). "Pulmonary Administration of Gentamicin During Liquid Ventilation in a Newborn Lamb Lung Injury Model". Pediatrics. 100 (5): e5. doi:10.1542/peds.100.5.e5. ISSN   0031-4005. PMID   9346999.
  35. ↑ Wolfson, Marla R.; Greenspan, Jay S.; Shaffer, Thomas H. (1 April 1996). "Pulmonary Administration of Vasoactive Substances by Perfluorochemical Ventilation". Pediatrics. 97 (4): 449–455. doi:10.1542/peds.97.4.449. ISSN   0031-4005. PMID   8632927. S2CID   25787266.
  36. ↑ Kimless-Garber, D.B.; Wolfson, M.R.; Carlsson, C.; Shaffer, T.H. (May 1997). "Halothane administration during liquid ventilation". Respiratory Medicine. 91 (5): 255–262. doi: 10.1016/S0954-6111(97)90028-7 . PMID   9176643.
  37. ↑ Zelinka, M. A.; Wolfson, M. R.; Calligaro, I.; Rubenstein, S. D.; Greenspan, J. S.; Shaffer, T. H. (21 April 1997). "A comparison of intratracheal and intravenous administration of gentamicin during liquid ventilation". European Journal of Pediatrics. 156 (5): 401–404. doi:10.1007/s004310050625. ISSN   0340-6199. PMID   9177987. S2CID   13135927.
  38. ↑ Lisby, Dee Ann; Ballard, Philip L.; Fox, William W.; Wolfson, Marla R.; Shaffer, Thomas H.; Gonzales, Linda W. (20 May 1997). "Enhanced Distribution of Adenovirus-Mediated Gene Transfer to Lung Parenchyma by Perfluorochemical Liquid". Human Gene Therapy. 8 (8): 919–928. doi:10.1089/hum.1997.8.8-919. ISSN   1043-0342. PMID   9195214.
  39. ↑ Cullen, A.B.; Cox, C.A.; Hipp, S.J.; Wolfson, M.R.; Shaffer, T.H. (Nov 1999). "Intra-tracheal delivery strategy of gentamicin with partial liquid ventilation". Respiratory Medicine. 93 (11): 770–778. doi: 10.1016/S0954-6111(99)90261-5 . PMID   10603625.
  40. ↑ Chappell, S.E.; Wolfson, M.R.; Shaffer, T.H. (Jul 2001). "A comparison of surfactant delivery with conventional mechanical ventilation and partial liquid ventilation in meconium aspiration injury". Respiratory Medicine. 95 (7): 612–617. doi: 10.1053/rmed.2001.1114 . PMID   11453320.
  41. ↑ Costantino, Maria-Laura; Shaffer, Thomas; Wauer, Roland R.; Rüdiger, Mario (July 2006). "The 5th European Symposium on Perfluorocarbon (PFC) Application". ASAIO Journal. 52 (4): 483–484. doi:10.1097/00002480-200607000-00021. ISSN   1058-2916. PMID   16883132.
  42. ↑ Hirschl, R. B.; Pranikoff, T.; Wise, C.; Overbeck, M. C.; Gauger, P.; Schreiner, R. J.; Dechert, R.; Bartlett, R. H. (1996-02-07). "Initial experience with partial liquid ventilation in adult patients with the acute respiratory distress syndrome". JAMA. 275 (5): 383–389. doi:10.1001/jama.1996.03530290053037. ISSN   0098-7484. PMID   8569018.
  43. ↑ Darwin, MG (1996). "Liquid ventilation: A bypass on the way to bypass". BPI Tech Briefs. 19.
  44. ↑ Harris, SB; Darwin, MG; Russell, SR; O'Farrell, JM; et al. (2001). "Rapid (0.5°C/min) minimally invasive induction of hypothermia using cold perfluorochemical lung lavage in dogs". Resuscitation. 50 (2): 189–204. doi:10.1016/S0300-9572(01)00333-1. PMID   11719148.
  45. ↑ Wolfson, Marla R.; Malone, Daniel J.; Wu, Jichuan; Hoffman, John; Rozenberg, Allan; Shaffer, Thomas H.; Barbut, Denise (Jun 2008). "Intranasal Perfluorochemical Spray for Preferential Brain Cooling in Sheep". Neurocritical Care. 8 (3): 437–447. doi:10.1007/s12028-008-9064-0. ISSN   1541-6933. PMID   18266110. S2CID   424891.
  46. ↑ Castrén, Maaret; Nordberg, Per; Svensson, Leif; Taccone, Fabio; Vincent, Jean-Louise; Desruelles, Didier; Eichwede, Frank; Mols, Pierre; Schwab, Tilmann (17 Aug 2010). "Intra-Arrest Transnasal Evaporative Cooling: A Randomized, Prehospital, Multicenter Study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness)". Circulation. 122 (7): 729–736. doi: 10.1161/CIRCULATIONAHA.109.931691 . ISSN   0009-7322. PMID   20679548.
  47. ↑ Busch, H.-J.; Eichwede, F.; Födisch, M.; Taccone, F.S.; Wöbker, G.; Schwab, T.; Hopf, H.-B.; Tonner, P.; Hachimi-Idrissi, S. (Aug 2010). "Safety and feasibility of nasopharyngeal evaporative cooling in the emergency department setting in survivors of cardiac arrest". Resuscitation. 81 (8): 943–949. doi:10.1016/j.resuscitation.2010.04.027. PMID   20627524.
  48. ↑ Lippsett, Lonny (5 April 2005). "Even Sperm Whales Get the Bends". Oceanus. 44 (1). Archived from the original on 5 June 2010. Retrieved 3 August 2010.
  49. ↑ Kylstra, J. A. (Sep 1974). "Liquid breathing". Undersea Biomedical Research. 1 (3): 259–269. ISSN   0093-5387. PMID   4619862.
  50. 1 2 Matthews, W. H.; Kylstra, J. A. (Jun 1976). "A fluorocarbon emulsion with a high solubility for CO2". Undersea Biomedical Research. 3 (2): 113–120. ISSN   0093-5387. PMID   951821.
  51. ↑ Miyamoto, Yoshimi; Mikami, Tomohisa (1976). "Maximum Capacity Of Ventilation And Efficiency Of Gas Exchange During Liquid Breathing In Guinea Pigs". The Japanese Journal of Physiology. 26 (6): 603–618. doi:10.2170/jjphysiol.26.603. ISSN   1881-1396. PMID   1030748. S2CID   21853061.
  52. ↑ Sherwood, Lauralee; Klandorf, Hillar; Yancey, Paul H. (2005). Animal Physiology: From Genes to Organisms. Southbank, Victoria, Australia: Thomson/Brooks/Cole. ISBN   978-0-534-55404-0. OCLC   224468651.
  53. ↑ Koen, Peter A; Wolfson, Marla R; Shaffer, Thomas H (Sep 1988). "Fluorocarbon Ventilation: Maximal Expiratory Flows and CO2 Elimination". Pediatric Research. 24 (3): 291–296. doi: 10.1203/00006450-198809000-00003 . ISSN   0031-3998. PMID   3145482.
  54. ↑ Matthews, W. H.; Balzer, R. H.; Shelburne, J. D.; Pratt, P. C.; Kylstra, J. A. (Dec 1978). "Steady-state gas exchange in normothermic, anesthetized, liquid-ventilated dogs". Undersea Biomedical Research. 5 (4): 341–354. ISSN   0093-5387. PMID   153624.
  55. ↑ Taylor, Jerome (20 November 2010). "Into the abyss: The diving suit that turns men into fish" . No. 20 November 2010. Independent Print Ltd. The Independent. Archived from the original on 2022-06-14. Retrieved 20 October 2015.
  56. ↑ Artificial gills for deep diving without incurring the bends and for scavenging O2 from and dispelling CO2 into water or thin air US Patent #8,631,788, published 21 Jan 2014.
  57. ↑ Hoepfner, Michael T.; Schultz, Marian C.; Schultz, James T. (Winter 2004). "Libelle Self-Contained Anti-G Ensemble: Overcoming Negative Transfer". The Journal of Aviation/Aerospace Education and Research. 13 (2). Daytona Beach, FL: Embry-Riddle Aeronautical University. OCLC   844961259.
  58. ↑ Guyton, Arthur C. (1986). "Aviation, Space, and Deep Sea Diving Physiology". Textbook of Medical Physiology (7th ed.). W. B. Saunders Company. p. 533.
  59. ↑ Advanced Concepts Team (2007-04-24). "Liquid Ventilation and Water Immersion". esa.int. Retrieved 2024-03-26.
  60. ↑ Westerfeld, Scott (2003). The Risen Empire. Little, Brown Book. ISBN   978-0-7653-0555-8.
  61. ↑ McNeill, Graham (2008). Mechanicum: war comes to Mars. Horus Heresy. Vol. 9. Cover art & illustration by Neil Roberts; map by Adrian Wood (1st UK ed.). Nottingham, UK: Black Library. pp. 64, 149. ISBN   978-1-84416-664-0. The amniotic tanks are referenced in several other places in the novel.
  62. ↑ Cixin, Liu (2008). The Dark Forest. Head of Zeus. ISBN   978-1784971595.
  63. ↑ van Eekhout, Greg (2014). California Bones. Macmillan. ISBN   978-0765328557.
  64. ↑ Harmetz, Aljean (August 6, 1989). "'The Abyss': A Foray Into Deep Waters". New York Times .
  65. ↑ "About Capsuleers - EVE Fiction - EVE Online Forums".
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.