ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Antonio F. Corno
Enrico Ferrari
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Corno, A. F.
Right arrow Articles by von Segesser, L. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Corno, A. F.
Right arrow Articles by von Segesser, L. K.
Related Collections
Right arrow Cardiac - pharmacology

Ann Thorac Surg 2004;78:956-960
© 2004 The Society of Thoracic Surgeons

Original article: cardiovascular

Myocardial and pulmonary effects of aqueous oxygen with acute hypoxia

Antonio F. Corno, MD, FRCS*, Yves Boone, RN, Iker Mallabiabarrena, PhD, Monique Augstburger, RN, Piergiorgio Tozzi, MD, Enrico Ferrari, MD, Ludwig K. von Segesser, MD, FACS

Department of Cardiovascular Surgery, Centre Hospitalier Universitaire Vaudo, Lausanne, Switzerland

Accepted for publication March 16, 2004.

* Address reprint requests to Dr Corno, Department of Cardiovascular Surgery, Centre Hospitalier Universitaire Vaudois, 46 Rue du Bugnon, Lausanne, Switzerland
antonio.corno{at}chuv.hospvd.ch

Presented at the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 26–28, 2004.


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Discussion
 References
 
BACKGROUND: The purpose of this paper was to evaluate myocardial and pulmonary effects of aqueous oxygen (AO) delivered directly into the pulmonary circulation in acute hypoxia.

METHODS: Six calves (2 months old, 68.0 ± 2.2 kg) after general anesthesia, mechanical ventilation, and median sternotomy underwent total right heart bypass using fixed flow with continuous pressure and blood gas measurements in carotid and femoral arteries, left atrium, the coronary sinus and PA. Measurements of systemic and PA pressures and O2 saturations; myocardial O2 atrioventricular (AV) differences; and O2 extraction were made. After base line measurements, hypoxic ventilation reducing the mean arterial PO2 from 277 ± 102 mm Hg to 47 ± 4 mm Hg (p < 0.0005) was maintained for 30 minutes. Without changes in the hypoxic ventilation (mean arterial PO2 = 49 ± 11 mm Hg) 3 ml/min of hyperbaric aqueous oxygen (AO = oxygen diluted in saline solution) was administered into the PA for 30 minutes. Pulmonary blood flow was maintained during the entire experiment (3.7 ± 0.3 L/min).

RESULTS: Hypoxic ventilation significantly raised (p < 0.05) the systolic (30 ± 7 vs 21 ± 4 mm Hg), diastolic (20 ± 6 vs 12 ± 3 mm Hg), and mean (23 ± 7 vs 15 ± 3 mm Hg) PA pressure; PA/systemic pressure ratio for systolic (0.37 ± 0.08 vs 0.25 ± 0.06) and mean (0.56 ± 0.19 vs 0.29 ± 0.11) pressures; and pulmonary vascular resistance (PVR) (5.63 ± 1.06 vs 3.53 ± 0.75 U). Aqueous oxygen (AO) infusion significantly reduced (p < 0.05) the values obtained with hypoxic ventilation; systolic (23 ± 5 vs 30 ± 7 mm Hg), diastolic (11 ± 4 vs 20 ± 6 mm Hg), and mean (14 ± 3 vs 23 ± 7 mm Hg) PA pressure; PA/systemic pressure ratio for systolic (0.25 ± 0.05 vs 0.37 ± 0.08) and mean pressures (0.29 ± 0.12 vs 0.56 ± 0.19); and PVR (3.41 ± 1.01 vs 5.63 ± 1.06 U). AO infusion in the pulmonary circulation did not influence the myocardial O2 atrioventricular (AV) difference or the O2 extraction.

CONCLUSIONS: Infusion of hyperbaric AO solution into the PA can completely reverse the negative effects of acute hypoxia on the pulmonary circulation without affecting the myocardial metabolism.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Discussion
 References
 
Congenital heart defects with left-to-right shunt and increased pulmonary blood flow, congenital, or acquired cardiac diseases with pulmonary venous hypertension, pathologies of the respiratory system, chronic hypoxemia, chronic thrombotic and/or embolic diseases, and a variety of miscellaneous causes can lead to vasoconstriction and structural remodeling of the pulmonary arterial vessels including thickness of adventitial and medial layers and muscularization of precapillary vessels causing pulmonary hypertension [1–3].

The combination of pulmonary vasoconstriction and vascular remodeling, coupled with increased hematocrit, results in pulmonary hypertension and subsequently right ventricular hypertrophy [4, 5]. Whereas prolonged pulmonary hypertension may result in irreversible vascular lesions leading to pulmonary vascular obstructive disease and the corresponding clinical pattern of the Eisenmenger syndrome [6–9], in patients with congenital heart defects the severity of the vascular remodeling in the pulmonary vessels seems to be in direct correlation with the increase of the pulmonary blood flow, the pressure and oxygen saturation at whom it is delivered, and the duration [10].

The currently available treatments for pulmonary hypertension including continuous oxygen administration and vasodilator therapy with either calcium antagonists, prostaglandins, prostacyclins, inhaled nitric oxide, and oral sildenafil provide suboptimal results with the exception of specific acute or chronic circumstances [1, 11]. Considering that in a previous experimental study [12] we observed that acute hypoxic pulmonary hypertension can be reduced by delivering hyperbaric oxygen solution (mean value of PO2 between 600 and 800 mm Hg) directly into the pulmonary circulation, we decided to evaluate the effects of the same treatment, but this time with fixed pulmonary blood flow, on the pulmonary circulation and on the myocardium.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Discussion
 References
 
After induction of general anesthesia and tracheal intubation with mechanical ventilation, six calves, 2 months old, 68.0 ± 2.2 kg, underwent chest opening through median sternotomy. Through longitudinal pericardial opening for exposure, the superior and inferior vena cava were dissected free and controlled with rubber tourniquets. After heparin IV administration (4 mg/kg of body weight, Liquemin; Hoffman-La Roche, Basel, Switzerland), a circuit for right heart bypass was established between two metal tip venous cannulas (DLP, Medtronic, Minneapolis, MN) separately introduced in superior and inferior vena cava and with an arterial cannula (Terumo, Cardiovascular Systems Corp., Ann Arbor, MI) introduced in the proximal PA (PA). Venous and pulmonary arterial cannulas were connected with a standard 1/2-inch to 3/8-inch polyvinylchloride tubing circuit primed with crystalloid solution (NaCl 104 mMol/L, KCl 5.4 mMol/L, CaCl2 1.6 mMol/L, MgCl 1 mMol/L, Na lactate 27 mMol/L, NaHCO3 50 mMol/L) with a roller pump (Stöckert, Sorin Biomedical, Irvine, CA) in the middle. The activated clotting time (ACT, Hemochron, International Technidyne Corp., Edison, NJ) was maintained above 400 seconds throughout the experiment. No additional blood was transfused.

Total right heart bypass was obtained by snaring the rubber tourniquets around the superior and inferior vena cava and draining the total systemic venous return (with the exception of the coronary sinus return) to the roller pump with restitution of the blood to the main PA.

Catheters for continuous pressure and blood gas measurements were directly inserted in carotid and femoral arteries, the left atrium, the coronary sinus, and the PA (Fig 1) . The presence of intracardiac shunts as well as of patent ductus arteriosus was ruled out at the beginning of the experiments.



View larger version (114K):
[in this window]
[in a new window]
  		Fig 1. Experimental setup with chest and pericardium open and all cannulas for right heart bypass and all catheters for pressures and saturations measurements already in place. (AO cath = aqueous oxygen infusion catheter; IVC c = inferior vena cava cannula; LA cath = left atrial catheter; PA = pulmonary artery; PA c = pulmonary artery cannula; PA cath = pulmonary artery catheter; RV = right ventricle; CS cath = coronary sinus catheter; SVC c = superior vena cava cannula.)

 
Instrumentation
Pressure measurement
Continuous pressure values were obtained connecting the systemic and PA catheters, as well as the coronary sinus and left atrial catheters, to high-fidelity pressure probes (Mikro-Tip, model MPC-500; Millar Instruments, Inc, Houston, TX) with a pressure range of –50 mm Hg to 300 mm Hg and a sensitivity of 5 µV · V · mm Hg. The ratio between PA and systemic pressure for values of systolic and mean pressures was calculated.

Pulmonary blood flow measurements
Once the animal was on total right heart bypass, after snaring the superior and inferior vena cava, the total pulmonary blood flow corresponded to the flow read of the roller pump.

Blood gas measurements
The pH, oxygen, and carbon partial pressure from the coronary sinus and left atrial catheters were continuously measured and displayed with an in-line gas monitoring system (CDI-500, Terumo, 3 mol/L; Health Care, Ann Arbor, MI) and the data read and recorded with a data acquisition system (LabView 6; National Instruments, Austin, TX). Blood gases were double-checked for correspondence of every recording of the hemodynamic parameters with analysis (ABL 700 analyzer; Radiometer Medical A/S, Copenhagen, Denmark) of blood samples obtained from the coronary sinus and femoral artery, respectively, for pulmonary and systemic circulation.

Evaluation
Pulmonary vascular resistance
The value was calculated with the following formula: pulmonary vascular resistance (PVR) = (mean PA pressure – mean left atrial pressure)/pulmonary blood flow.

Myocardial metabolism
The myocardial arteriovenous difference for oxygen was calculated with the values of oxygen saturation obtained by the arterial systemic and coronary sinus catheters; the myocardial oxygen extraction was calculated with the formula: myocardial oxygen extraction = (arterial oxygen saturation – coronary sinus oxygen saturation)/arterial oxygen saturation.

After the base line measurements were performed with the animal already on total right heart bypass, hypoxic pulmonary hypertension was obtained through hypoxic ventilation reducing the mean arterial PO2 from 277 ± 102 mm Hg to 47 ± 4 mm Hg (p < 0.0005) with continuous reading of the monitored parameters. After 30 minutes with hypoxic ventilation, new samples for blood gases were taken and all the parameters were recorded.

At this point without any change in the hypoxic ventilation (the mean arterial PO2 was maintained at 49 ± 11 mm Hg, not significant [NS]), 3 mL/min of hyperbaric aqueous oxygen (AO = oxygen diluted in saline solution with a concentration of 0.82 mL of oxygen/mL lactated Ringer's solution, TherOx Inc, Irvine, CA) were added to 72 mL/min of blood withdrawn from the carotid artery and, via a custom syringe pump (TherOx Inc, Irvine, CA), infused directly into the PA for 30 minutes with continuous reading of the monitored parameters. At the end of the 30 minutes of AO infusion, after new samples for blood gases were taken and all the parameters were recorded, the experiments were ended and the animals were sacrificed.

All animals were treated and all experiments were conducted in accordance with the guidelines set forth by the U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health (Bethesda, MD) [13]. The protocol was approved by the institutional Committee on Animal Research.

Student's t test was used for statistical evaluation. Data are expressed as mean ± standard deviation (SD). The significance level was p = 0.05.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Discussion
 References
 
The pulmonary blood flow was maintained as stable during the entire experiment (3.7 ± 0.3 L/min) without any addition of blood, because the values of hemoglobin remained stable during the entire protocol. In all experiments 30 minutes of hypoxic ventilation significantly raised the values of systolic, diastolic, and mean PA pressure, PA/systemic pressure ratio for systolic and mean pressures, and PVR (Table 1). After another 30 minutes of the same hypoxic ventilation, but with AO infusion, all of the values obtained with hypoxic ventilation only (systolic, diastolic, and mean PA pressure, PA/systemic pressure ratio for systolic and mean pressures, and PVR) returned as not statistically different from base line values obtained without hypoxia (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Hemodynamic Parameters

 
Despite an evident reduction of the myocardial arteriovenous difference for oxygen during hypoxia (from 63%–46%, p < 0.01) caused by the wanted reduction of the systemic oxygen saturation, AO infusion in the pulmonary circulation did not influence the myocardial O2 arteriovenous difference (from 46%–48%, not significant [NS]) or the O2 extraction (from 59%–63%, NS) during acute hypoxia (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2. Myocardial Metabolic Parameters

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Discussion
 References
 
Oxygen administration by ventilation may either fail to correct arterial hypoxemia with the associated pulmonary hypertension or may be limited by the potential for pulmonary toxicity at high inspired oxygen concentration [14].

The only possibility currently available for introducing oxygen into blood requires its diffusion across an artificial gas–liquid interface. Mass transport of oxygen by diffusion is inherently slow, so that a relatively large surface area for contact of the two phases is required in both the extracorporeal and intravascular oxygenators [15–17]. Therefore such devices are inherently bulky and prolonged contact with blood over a broad surface area may be associated with a variety of complications [18, 19].

A bubble-free method has been developed for introducing oxygen dissolved at elevated partial pressures in physiologic crystalloid solutions (aqueous oxygen; TherOx Inc, Irvine, CA) at rapid velocity through capillary tubes in vitro into host liquids at ambient pressure [20]. The stabilized aqueous oxygen solution can be mixed with blood to create a bubble-free hyperoxemic blood perfusate that can be safely infused to increase the local oxygen tension to hyperbaric levels with a small amount of carrier solution [21].

So far the main experimental and clinical applications of this technique have been in the field of myocardial ischemia. Positive results have been obtained with intravascular administration of hyperbaric oxygen during myocardial reperfusion, in particular regarding the reduction of the myocardial injury associated with ischemia/reperfusion in both experimental [22–24] and clinical studies [25–27]. Recently intravascular administration of hyperbaric oxygen has proven to also be successful as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model [28].

In a previous experimental study we tested the hypothesis if an off-label use of hyperbaric oxygen solution was able to treat pulmonary hypertension with a similar protocol, but without total right heart bypass, therefore leaving to the pulmonary circulation the possibility of modifying pulmonary blood flow and resistance [12]. In our previous experience the administration of a minimal amount of hyperbaric oxygen solution directly into the pulmonary circulation allowed for the correction of all the hemodynamic parameters negatively affected by the hypoxic ventilation with return to the values obtained at base line with normal ventilation.

In the current experimental study we extended our observations to the administration of AO during total right heart bypass and again, despite the minimal amount used (3 mL/min mixed with a fixed pulmonary blood flow of 3.7 ± 0.3 L/min maintained during the hypoxic ventilation), the relief of pulmonary hypertension was confirmed. We also decided to evaluate the influence on the myocardial metabolism of the infusion of hyperbaric oxygen solution during the hypoxic ventilation with pulmonary hypertension. Our results did not indicate any considerable change in the myocardial arteriovenous difference of oxygen or in the oxygen extraction during the AO administration. This observation confirmed that the positive results obtained with regard to the pulmonary circulation are independent of the effects on the myocardial metabolism.

Our current experimental observations are consistent with our initial hypothesis that a minimal amount of oxygen is sufficient to reverse the pulmonary vasoconstriction induced by severe hypoxia provided that the oxygen is available by direct administration into the pulmonary circulation. We are well aware that the amount of 3 mL/min used in our experimental study could represent a substantial volume overload if applied to a subject with a much smaller body weight and size. In view of potential clinical applications in a subject such as a neonate or a small infant, one or more of the currently available solutions to reduce the volume overload have to be taken into consideration.

Only the acute effects of AO administration have been studied in an acute situation with pulmonary hypertension artificially created with 30 minutes of hypoxic ventilation on total right heart bypass. The consequences of AO administration after induction of chronic hypoxia [29] or in the presence of established pulmonary hypertension with histologic pulmonary vascular lesions [10] should be evaluated

Despite the evident experimental benefits of AO administration on the hemodynamic parameters, reactive oxygen species generation upon the intravascular introduction of oxygen remains a potential concern [30]. The relationship between oxygen partial pressure in the reperfused tissues and reactive oxygen species production is likely to be quite complex, but nevertheless it is possible that oxygen toxicity may occur with longer periods of treatment. If this were to be demonstrated, the conventional strategies with oxygen free radical scavengers should be taken into consideration.

In conclusion our experimental study demonstrated that acute infusion of hyperbaric AO solution into the pulmonary circulation can completely reverse the negative hemodynamic effects of hypoxia during total right heart bypass without interferences on the myocardial oxygen metabolism. These observations can lead to the extension of experimental studies with AO usage in more severe and chronic situations to evaluate the potential clinical applications of this available technology. If the results observed with acute hypoxia could be confirmed in a chronic hypoxic model, the potential administration of the hyperoxic solution into the pulmonary circulation through a simple central venous line could be taken into consideration for patients in the intensive care unit because of respiratory insufficiency attributable to cardiac or pulmonary diseases with subsequent hypoxia and/or pulmonary hypertension.


   Discussion
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Discussion
References
 
DR SCOTT M. BRADLEY (Charleston, SC): Could you tell us a bit more about what exactly the aqueous oxygen solution consists of? Is it a mixture of blood and a carrier with oxygen within it?

DR CORNO: The oxygen can be mixed with any type of saline solution. We simply use the saline solution that is available from our pharmacy at the hospital, but it can be used in any physiologic solution. It is mixed in this cartridge of the chamber with a particular system allowing a bubbleless system, because the oxygen exhibits very high pressure, 30 bar, and is diffused in the saline solution by a system with glass (or better silica) capillary microtubes having an internal diameter less than 1 µm. This is the way to prevent the formation of bubbles. There are, in fact, nanobubbles, but they are insignificant for clinical consequences. Then, this hyperbaric oxygen solution is mixed with the blood that we obtained from the animal into the coronary circulation from the patient using two catheters—one drawing 72 ml/min of blood and the other reinfusing 72 ml of blood plus 3 ml of this hyperbaric oxygen solution.

DR BRADLEY: What is the PO2 of aqueous oxygen?

DR CORNO: It is between 600 and 800 mm Hg. So it is really very high partial pressure.

DR BRADLEY: And how stable is the solution over time? How soon do you need to infuse it after it is made?

DR CORNO: Well, it is practically infused immediately, because the mixture is done in the cartridge and it is quickly connected to the circuit coming from the patient and going back to the patient. So we do not prepare this solution and leave it in place. Simply the machine is started when we start the application. The device available for the patient, until now, which is the same we use in animals, allows the use of one single cartridge for 90 minutes. So it is for acute usage. In fact, it has been devised for adult cardiologists to use as a protection during PTCA dilatation for coronary arteries to protect the distal myocardium. We are using this in animals as off-label usage.

DR ANDREW C. FIORE (St. Louis, MO): I understand that the flow into the lung was controlled, but was the hematocrit the same in all patients?

DR CORNO: Well, we were studying it in animals, not in patients.

DR FIORE: I mean in animals.

DR CORNO: So we did not use any blood. We filled the circuit from the vena cava to the aortic cannula in the PA with saline solution. We never add any blood to the system. But it is a short duration experiment, 90 minutes, so we did not need to add any blood. The hemoglobin was quite stable during the procedure.

DR FIORE: I just have to ask this question. Was the atrial septum intact and was the ductus arteriosus occluded in all of these calves?

DR CORNO: Well, of course. With the echo and inspection we excluded any atrial septal defect and any patent ductus arteriosus. Because at 2 months of age we can have animals with patent ductus arteriosus, so this had been excluded at the beginning.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Discussion
 References
 

  1. Gibbs JS. Recommendations on the management of pulmonary hypertension in clinical practice. Heart. 2001;86(Suppl I):1–13[Free Full Text]
  2. Hopkins WE. Severe primary pulmonary hypertension in congenital heart disease: a review of Eisenmenger syndrome. Curr Opin Cardiol. 1995;10:517–523[Medline]
  3. Hislop A, Reid L. New findings in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension. Br J Path. 1976;57:542–554
  4. Corno AF, Milano G, Samaja M, et al. Chronic hypoxia: a model for cyanotic congenital heart defects. J Thorac Cardiovasc Surg. 2002;124:105–112[Abstract/Free Full Text]
  5. Corno AF, Milano G, Morel S, et al. Hypoxia: unique myocardial morphology? J Thorac Cardiovasc Surg 2004;127:1301–8
  6. Vongpatanasin W, Brickner ME, Hillis LD, et al. The Eisenmenger syndrome in adults. Ann Intern Med. 1998;128:745–755[Medline]
  7. Daliento L, Somerville J, Presbitero P, et al. Eisenmenger syndrome. Factors relating to deterioration and death. Eur Heart J. 1998;19:1845–1855[Abstract/Free Full Text]
  8. Cantor WJ, Harrison DA, Moussadji JS, et al. Determinants of survival and length of survival in adults with Eisenmenger syndrome. Am J Cardiol. 1999;84:677–681[Medline]
  9. Oya H, Nagaya N, Uematsu M, et al. Poor prognosis and related factors in adults with Eisenmenger syndrome. Am Heart J. 2002;143:739–744[Medline]
  10. Corno AF, Tozzi P, Genton CY, et al. Surgically induced unilateral pulmonary hypertension: time related analysis of a new experimental model. Eur J Cardiothorac Surg. 2003;23:513–517[Abstract/Free Full Text]
  11. Ghofrani HA, Rose F, Schermuly RT, et al. Oral Sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol. 2003;42:158–164[Medline]
  12. Corno AF, Boone Y, Mallabiabarrena I, et al. Aqueous oxygen: the solution to relief hypoxic pulmonary hypertension. Eur J Cardiothorac Surg (submitted for publication)
  13. Principles of Laboratory Animals (formulated by the National Society of Medical Research). Guide for the Use and Care of Laboratory Animals. Publication No. 85-23. Bethesda, MD: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, Revised 1985
  14. Huber GL, Drath DB. Pulmonary oxygen toxicity. Gilbert DL. Oxygen and Living Processes: An Interdisciplinary Approach. New York: Springer-Verlag; 1981. p. 273–357
  15. Stinkens D, Himpe D, Thyssen P, et al. Clinical evaluation of the oxygenation capacity and controllability of 15 commercially available membrane oxygenators during alpha-state regulated hypothermic cardiopulmonary bypass. Perfusion. 1996;11:471–480[Abstract/Free Full Text]
  16. Voorhees ME, Brian BF. Blood-gas exchange devices. Int Anesthesiol Clin. 1996;34:29–45[Medline]
  17. Sim KM, Evans TW, Keogh BF. Clinical strategies in intravascular gas exchange. Artif Organs. 1996;20:807–810[Medline]
  18. Fukutomi M, Kobayashi S, Niwaya K, et al. Changes in platelet, granulocyte, and complement activation during cardiopulmonary bypass using heparin-coated equipment. Artif Organs. 1996;20:767–776[Medline]
  19. Martin W, Carter R, Tweddel A, et al. Respiratory dysfunction and white cell activation following cardiopulmonary bypass: comparison of membrane and bubble oxygenators. Eur J Cardiothorac Surg. 1996;10:774–783[Abstract/Free Full Text]
  20. Brereton GJ, Crilly RJ, Spears JR. Nucleation in small capillary tubes. Chem Phys. 1998;230:253–265
  21. Spears JR, Wang B, Wu X, et al. Aqueous oxygen: a highly O2-supersaturated infusate for regional correction of hypoxemia and production of hyperoxemia. Circulation. 1997;96:4385–4391[Abstract/Free Full Text]
  22. Spears JR, Prcevski P, Wu X, et al. Hyperoxemic perfusion with aqueous oxygen improves left ventricular function during experimental MI reperfusion. Circulation. 1997;96(Suppl I):364
  23. Kantor B, McKenna CJ, Camrud AR, et al. Coronary reperfusion with aqueous oxygen improves left ventricular ejection fraction and may reduce mortality in an ischemic porcine model. Am J Cardiol. 1998;82(Suppl 7):86S
  24. Spears JR, Henney C, Prcevski P, et al. Aqueous oxygen hyperbaric reperfusion in a porcine model of myocardial infarction. J Invas Cardiol. 2002;14:160–166[Medline]
  25. Cameron AJV, Hutton ACF, Murdoch WR. Hemodynamic and metabolic effects of hyperbaric oxygen in myocardial infarction. Lancet. 1966;2:833–837[Medline]
  26. Dixon SR, Bartorelli AL, Marcovitz PA, et al. Initial experience with hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction. Results of a pilot study utilizing intracoronary aqueous oxygen therapy. J Am Coll Cardiol. 2002;39:387–392[Medline]
  27. Bartorelli AL. Hyperoxemic perfusion for treatment of reperfusion microvascular ischemia in patients with myocardial infarction. Am J Cardiovasc Drugs. 2003;3:253–263[Medline]
  28. Petre PM, Baciewicz FA, Tigan S, et al. Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model. J Thorac Cardiovasc Surg. 2003;125:85–95[Abstract/Free Full Text]
  29. Corno AF, Milano G, Samaja M, et al. Chronic hypoxia: a model for cyanotic heart defects. J Thorac Cardiovasc Surg. 2002;124:105–112[Abstract/Free Full Text]
  30. McCord JM. Oxygen-derived radicals: a link between reperfusion injury and inflammation. Fed Proc. 1987;46:2402–2406[Medline]



This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
A. Tabuchi, M. Mertens, H. Kuppe, A. R. Pries, and W. M. Kuebler
Intravital microscopy of the murine pulmonary microcirculation
J Appl Physiol, February 1, 2008; 104(2): 338 - 346.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Antonio F. Corno
Enrico Ferrari
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Corno, A. F.
Right arrow Articles by von Segesser, L. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Corno, A. F.
Right arrow Articles by von Segesser, L. K.
Related Collections
Right arrow Cardiac - pharmacology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS