(Circulation. 1997;96:4385-4391.)
© 1997 American Heart Association, Inc.
Articles |
Aqueous Oxygen
A Highly O2-Supersaturated Infusate for Regional Correction of Hypoxemia and Production of Hyperoxemia
From the Cardiovascular Research Laboratory, Department of Medicine, Division of Cardiology, Harper Hospital/Wayne State University School of Medicine, Detroit, and the Department of Mechanical Engineering, Michigan State University, Lansing (G.J.B.), Mich.
Correspondence to J. Richard Spears, MD, Wayne State University School of Medicine, Louis M. Elliman Research Bldg, Room 1107, 421 E Canfield Rd, Detroit, MI 48201. E-mail spears{at}oncvx1.roc.wayne.edu
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Abstract |
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Background High levels of hyperoxemia may have utility in the treatment of regional tissue ischemia, but current methods for its implementation are impractical. A catheter-based method for infusion of O2, dissolved in a crystalloid solution at extremely high concentrations, ie, 1 to 3 mL O2/g (aqueous oxygen [AO]), into blood without bubble nucleation was recently developed for the potential hyperoxemic treatment of regional tissue ischemia.
Methods and Results To test the hypotheses that hypoxemia is correctable and that hyperoxemia can be produced locally by AO infusion, normal saline equilibrated with O2 at 3 MPa (30 bar; 1 mL O2/g) was delivered into arterial blood in two different animal models. In 15 New Zealand White rabbits with systemic hypoxemia, AO was infused into the midabdominal aorta at 1 g/min. Mean distal arterial PO2 increased to 236±113 and 593±114 mm Hg on 1-hour periods of air and O2 breathing, respectively, from a baseline of 70±10 mm Hg (P<.01). In contrast, infusion of ordinary normal saline in a control group (n=7) had no effect on arterial PO2. No differences between groups (P>.05) in temporal changes in blood counts and chemistries were identified. In 10 dogs, low coronary blood flow in the circumflex artery was delivered with a roller pump through the central channel of an occluding balloon catheter. Hypoxemic, normoxemic, and AO-induced hyperoxemic blood perfusates (mean PO2, 52±4, 111±22, and 504±72 mm Hg, respectively) were infused for 3-minute periods in a randomized sequence. Short-axis two-dimensional echocardiography demonstrated a significant decrease (P<.05) in left ventricular ejection fraction compared with baseline physiological values with low-flow hypoxemic and normoxemic perfusion but not with low-flow hyperoxemic perfusion.
Conclusions Intra-arterial AO infusion was effective in these models for regional correction of hypoxemia and production of hyperoxemia.
Key Words: oxygen • hypoxia • ischemia • catheterization
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Introduction |
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Oxygen administration by ventilation either may fail to correct arterial hypoxemia or may be limited by the potential for pulmonary toxicity at high inspired oxygen concentrations.1 This problem is more profound when regional tissue ischemia, associated with locally impaired blood flow, is superimposed on systemic hypoxemia. Currently, the only alternative means 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 extracorporeal and recently developed intravascular oxygenators.2–4 Such devices are therefore inherently bulky, and prolonged contact with blood over a broad surface area may be associated with a variety of problems.5–14
We recently developed a bubbleless method for introducing oxygen, dissolved at partial pressures of 3 to 10 MPa (30 to 100 bar) in physiological crystalloid solutions, ie, aqueous oxygen (AO), at a rapid velocity through capillary tubes in vitro into host liquids at ambient pressure.15–18 The corresponding concentration of oxygen in AO is 1 to 3 mL O2/g, which is an order of magnitude greater than the O2 carrying capacity of blood. Rapid dilution of the AO effluent with the host liquid during rapid mixing of the two liquids results in efficient oxygenation of hypoxemic liquids, because diffusion at a gas/liquid interface is not required. In the present study, the hypotheses were tested that regional arterial hypoxemia is correctable and that hyperoxemia can be produced experimentally in vivo with an AO infusion.
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Methods |
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Animal Models
Protocols were approved by the Wayne State University School of Medicine Institutional Review Board before initiation of studies. All animals were housed and studied in a facility approved by the American Association for Accreditation of Laboratory Animal Care. Humane care was provided to all animals in accordance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences (NIH publication 85–23, revised 1985).
Systemic Hypoxemia in Rabbits
Twenty-two New Zealand White female rabbits weighing 3.4 to 3.6
kg were anesthetized with ketamine 35 mg/kg IM and
xylazine 5 mg/kg IM, with additional quarter doses given
intravenously as needed thereafter. All rabbits were
allowed to breathe spontaneously throughout the course of the study.
The distal end of a 2.5-m-long fused silica capillary tube with a
75-µm ID (365-µm OD, Polymicro Technology, Inc) was advanced
antegrade to the midabdominal aorta from a carotid artery cutdown
approach. A gold marker band at the distal end of the tube permitted
its precise placement under fluoroscopic control (Precise Optics). A
polyethylene catheter (PE 90) was advanced retrograde to the distal
aorta from a femoral artery cutdown, and a similar catheter was
advanced to the distal inferior vena cava from a femoral
vein for withdrawal of blood samples. Heparin 100 U/kg was given
intravenously immediately after placement of the
catheters.
An infusion of normal saline at 1 g/min through the capillary tube was
performed in all animals during an initial 1 hour of air breathing and
a subsequent 1 hour of 100% oxygen breathing. The infusion was started
at each of the two FIO2 levels after
a constant arterial PO2
(
5 mm Hg) over at least a 10-minute period was confirmed.
The distal end of the catheter was withdrawn 2 to 3 cm proximally
immediately before the infusion on oxygen breathing. Otherwise, an
excessive rise in distal arterial blood
PO2 occurred, on the order of 900 to
1400 mm Hg, which was noted in a prior pilot study to
occasionally result in the formation of microbubbles. Systemic
hypoxemia was present in most of the animals on air breathing, very
likely as a result of a naturally occurring pneumonia
(Pasteurella multocida).19 Once
the infusion was initiated, arterial and venous blood
samples were obtained at 10-minute intervals for blood gas
analysis (model 1312, Instrumentation Laboratories). Unused
portions of blood samples were returned intravenously.
Additional blood samples were obtained before and after 1 and 2 hours
of the onset of the infusion for analysis of complete blood
counts and of a battery of chemistries. All analyses except
blood gas measurements and lipid peroxide levels (femoral venous blood,
K-Assay, Kamiya Biomedical Co) were performed by an independent
clinical laboratory.
In a treatment group of rabbits (n=15), the saline infusate contained 1 mL O2/g. The remainder of the rabbits (n=7) received saline alone and served as a control group. Although aortography was not performed routinely, in view of the fluid volume challenge superimposed on the saline infusion, it was performed in two additional rabbits in the treatment group before the infusion and immediately before its termination. Quantitative image analysis of digitized video images (3/4-in Sony recorder) recorded at a 2:1 magnification at the output phosphor was used20 to measure the luminal diameter of the distal aorta. A vessel phantom of known diameter filled with contrast medium, included in the radiographic field at the same level as the aorta, was used for calibration of the magnification factor. On completion of each study, the abdominal aorta, external iliac arteries, common femoral arteries, and random samples of skeletal muscle perfused with saline or AO injectates were harvested and placed in 10% neutral buffered formalin. Alcohol-dehydrated, paraffin-embedded, hematoxylin-eosin–stained sections were examined by light microscopy.
Dog Low-Flow Coronary Artery Perfusion Model
Under pentobarbital and morphine sulfate anesthesia
and after endotracheal intubation and placement of a volume-cycled
respirator, cutdowns were performed in 10 adult mongrel dogs (weight,
21±6 kg) over the midline cervical and bilateral inguinal regions.
Heparin 100 U/kg IV was given. An 8F guide catheter was advanced to the
left coronary ostium from a carotid arteriotomy, and a 6F dual
Millar catheter was advanced to the left ventricle from a femoral
arteriotomy. The distal transducer was used to monitor left
ventricular pressure and dP/dt, and the proximal one was
used to monitor aortic root pressure. All pressures and a lead II ECG
were continuously recorded on a physiological
recorder (model 2107–8890, Gould, Inc) throughout each study. An
8F Swan-Ganz catheter (Criticon) was advanced from the internal jugular
vein into the distal portion of the coronary sinus for blood
gas analysis on samples obtained intermittently.
A 4F Swan-Ganz catheter (Arrow) was advanced through the guide catheter
into the proximal circumflex artery in each dog. Inflation of the
balloon with air was used to occlude the circumflex artery for 3-minute
periods. Injection of 5 mL iohexol through the guide catheter was used
to confirm fluoroscopically that flow through the circumflex artery was
completely occluded and that the left mainstem artery was patent. After
two initial balloon occlusion periods separated by a 5-minute interval,
three more balloon occlusions were performed, with blood perfusion
through the central channel of the Swan-Ganz catheter at a flow rate of
10 to 20 mL/min. Previous experience with this model demonstrated that
resting circumflex coronary artery flow in similar-sized dogs
is 35 to 40 mL/min, so that the flow rate chosen
represented 30% to 50% of anticipated normal levels. For
each dog, the flow rate was the same during infusion of blood at three
different levels of arterial
PO2. Randomized assignment to
the different levels was used before initiation of blood perfusion. A
roller pump (model 7401 blood pump, B-D Drake Willock) and Tygon tubing
(ID 1/8 in) was used to withdraw blood from an external reservoir
filled with autologous blood and to deliver it to the proximal end of
the Swan-Ganz catheter. To obtain hypoxemic blood for the perfusion,
venous and arterial blood were mixed in a 1:1 ratio. AO
consisting of normal saline containing 1 mL
O2/g was infused through a silica capillary
tube (75 µm ID) at 1 g/min into arterial blood
within the reservoir until a PO2 of
500 mm Hg was achieved.
Immediately before and during the final 20 seconds of each balloon occlusion period, pressures and ECG were recorded at 25 mm/s, and two-dimensional transthoracic echocardiographic video recordings of the left ventricular short axis were obtained (model SZ-203-PA, 5-MHz probe, Aloka Co, Ltd). In our experience, this echocardiographic approach is superior to transesophageal ultrasound for examining posterior wall motion during circumflex occlusion–induced regional myocardial ischemia. From digitized end-diastolic (d) and end-systolic (s) video frames, relative areas (A) were determined automatically after manual delineation of the left ventricular endocardial border. Percent left ventricular ejection fraction (% LVEF) was determined as 100x[(Ad-As)/Ad].
On completion of each study, the heart was removed, the aortic root was flushed with saline, and after the myocardium was sectioned at 1-cm intervals from base to apex, the sections were placed in 10% neutral buffered formalin for processing for light microscopy as described above.
Preparation of AO
Normal saline (Baxter) was equilibrated with oxygen from a
medical-grade oxygen cylinder (Air Products; nominal purity
99.5%) at 3 MPa in a sterile 316 stainless steel 3.5-L reservoir at
22°C for at least 24 hours before use. The oxygenated
saline was delivered to the 75-µm-ID silica capillary tube at a
hydrostatic pressure (50 to 70 MPa) with a hydrostatic compressor (SC
Hydraulics) that provided a flow rate of 1 g/min at a velocity of 4
m/s though the tube. Collection of undiluted AO effluents at 3 MPa, in
a manner that allowed its decomposition under conditions that
approximate standard temperature and pressure, demonstrated an oxygen
concentration of 1 mL O2/g, which is the
same as that observed in previous in vitro studies at this partial
pressure.18 Immediately before AO infusion
through the silica tube into blood, each tube was flushed for several
minutes with ordinary normal saline at 70 MPa from a hydraulic
compressor operated in parallel to ensure the remove of surface gas
nuclei. The hydraulic compressor was used to deliver normal saline
alone in the control group of rabbits.
Data Analysis
ANOVA was used for prespecified comparisons, including blood gas
values, blood counts, and plasma chemistries between groups and over
time in the rabbit study and echocardiographic left
ventricular dimensions, hemodynamic
parameters, and ECG J-point elevation (referenced to the
preceding TP segment) between levels of perfusion (normal flow; no
perfusion; and either hypoxemic, normoxemic, or hyperoxemic perfusion)
in the dog study. Before comparisons of blood counts and laboratory
values, a correction derived from the change in hematocrit over time
was applied for hemodilution produced by the saline infusion in both
the control and treatment groups. A two-tailed, unpaired Student's t test was used to compare means between groups and
between time periods of normally distributed data, when ANOVA resulted
in a significant F test. A value of P<.05, after
application of a Bonferroni correction, was considered statistically
significant. Values are expressed as mean±SD.
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Results |
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Effect of AO Infusion in Hypoxemic Rabbits
On room air breathing, arterial and venous PO2 in distal blood samples increased during infusion of the aqueous O2 solution to a level similar to that achieved with 100% O2 breathing in the control group (Fig 1
). Arterial hypoxemia, which
was severe in many of the rabbits
(PO2 60 mm Hg in 3 and
80 mm Hg in 13 of the 15 rabbits), was corrected locally by
the infusion in all such animals (PO2
range, 106 to 445 mm Hg). On 100%
O2 breathing, an increase in the mean
arterial PO2 to
593±114 mm Hg from a baseline value of 330±109 mm
Hg was observed. In the treatment group, the mean venous
PO2 increased from 37±6 mm
Hg before the infusion to 48±5 mm Hg during the infusion on
air breathing and from a baseline of 51±8 to 69±11 mm Hg
during the infusion on oxygen breathing. No significant change in the
arterial or venous PO2
occurred over time in the control group on either air breathing (mean
arterial and venous PO2,
71±6 and 39±5 mm Hg, respectively) or oxygen breathing
(mean arterial and venous
PO2, 319±95 and 55±7 mm
Hg, respectively). All differences in mean arterial and
venous PO2 values during AO infusion,
compared with control group values and baseline values, were
significant at P.01.
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On the basis of the indicator dilution principle, intra-aortic blood flow during AO infusion at a known rate of O2 delivery was estimated from the distal arterial PO2, hemoglobin level, and O2 solubility in blood. The ratio of infusate to blood flow was found to vary between 0.01 and 0.02 in the treatment group.
There were no significant changes in either
PCO2 or pH during infusion of the
aqueous O2 solution compared with baseline
or control group values (P>.05). Compared with the
control group, there were no significant differences in changes in any
laboratory test other than PO2
(Table). Angiographic luminal diameter
measurements of the distal aorta by computer image processing differed
by <4% during AO infusion periods, compared with air and oxygen
breathing periods without the infusion, in the two rabbits studied. No
histopathological changes were noted by light microscopy in
formalin-fixed, hematoxylin-eosin–stained tissues perfused with
AO.
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Effect of AO Infusion on Low-Flow Coronary Ischemia
in Dogs
The mean PO2 values of
hypoxemic, normoxemic, and hyperoxemic perfusates were 52±4,
111±22, and 504±72 mm Hg, respectively. Mean values of left
ventricular systolic and diastolic
areas by two-dimensional echocardiography were
significantly smaller (by 27.1% and 13.4%, respectively) and % LVEF
was significantly greater (by 31.0%) during hyperoxemic low
coronary flow compared with hypoxemic low flow
(P<.05). In contrast, the mean improvements in
systolic (15.5%) and diastolic (6.3%) areas and
in % LVEF (16.2%) associated with normoxemic low flow, compared with
hypoxemic low flow, were not statistically significant
(P>.05).
Compared with mean baseline values of LVEF obtained immediately before
each low-flow perfusion period, mean LVEF associated with both
hypoxemic and normoxemic low flow was significantly depressed
(P<.05, Fig 2). In contrast,
mean LVEF during hyperoxemic low flow was not significantly different
from mean baseline values (P>.05).
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Mean coronary sinus PO2 values during hyperoxemic perfusion (28.8±8.5 mm Hg) were nearly the same as the mean value of baseline flow periods immediately before balloon occlusion and before active perfusion periods (29.0±7.1 mm Hg) and slightly higher than the mean values observed during normoxemic (25.8± 7.2 mm Hg) and hypoxemic perfusion (26.3±7.8 mm Hg), but these differences did not achieve statistical significance.
Although trends in improvement in hemodynamic parameters and ECG lead II J-point change from baseline were noted with increasing PO2 levels, these changes also were not statistically significant.
No histopathological changes were noted by light microscopy in hematoxylin-eosin–stained sections of the left ventricle in any of the animals.
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Discussion |
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Oxygen administration is a common adjunctive measure in the treatment of patients with acute ischemia of a major organ. However, systemic hypoxemia may not be correctable by a ventilatory route of administration in many patients with respiratory insufficiency. In addition, attempts to correct systemic hypoxemia or to induce arterial hyperoxemia with high levels of inspired oxygen tensions may result in pulmonary oxygen toxicity.1 As a result, for example, the duration of hyperbaric oxygen exposure, typically 2.0 to 2.5 bar, is usually limited to 90 min/d. Additional common problems with hyperbaric chambers include limited patient access, decompression periods required, middle ear barotrauma, and high cost. Alternatively, regional catheter-based arterial perfusion of hyperoxemic blood at PO2
1 bar could be performed with a
conventional oxygenator used in an extracorporeal circuit to treat
local tissue ischemia. Potential activation of coagulation
cascade components and induction of inflammatory cell
reactions5–14 very likely have been
deterrents to a clinical application with such an approach. The
relatively large priming volume required for preparation of a
conventional oxygenator, as well as the need for specialized personnel
for its operation, may also have hindered the development of its use
for regional hyperoxemic perfusion.
Oxygen is only sparingly soluble in water. At a
PO2 of 1 bar, the oxygen content of
water is 0.03 mL
O2/g.21 Bubble
formation is ordinarily prominent when the dissolved gas partial
pressure greatly exceeds hydrostatic pressure. However, under static
conditions, several groups have noted the absence of nucleation, on
release of hydrostatic pressure to atmospheric, in water equilibrated
with a variety of gases at extremely high partial
pressures,22–27 including oxygen at 140
bar.25 Stabilization of
heterogeneous (solid/liquid interface) gas nuclei by high
hydrostatic compression very likely contributed to these observations.
Ordinarily, cavitation thresholds are diminished by ejection of liquids
at high velocity.29 We found that
stabilization of surface nuclei near the exit port by the application
of high hydrostatic pressure and the use of capillary tubes of suitably
small dimensions permit ejection of water, equilibrated with oxygen at
a PO2 as high as 140 bar, into
aqueous liquids at ambient pressure without bubble
nucleation.15–18 An inverse relationship
was noted between capillary tube diameter and the maximum threshold of
metastability of the effluent. Predictions of a newly developed
heterogeneous nucleation model of
ours18 correlated well with empirical
observations, including the effect of temperature on nucleation
thresholds. An important conclusion of the model is that small ratios
of volume to surface area of liquid-confining spaces, such as within
the capillary tubes used to deliver gas-supersaturated solutions,
retard the formation of active surface nuclei. The high tensile
strength of water confined within small spaces, as noted by others in
widely disparate scientific
disciplines,22–32 is explicable for the
first time by the model.
The results of the present work support the hypothesis that an AO infusion can be used either to correct hypoxemia or to produce hyperoxemia on a regional basis. In the rabbit study, the mean arterial and venous oxygen tensions that were achieved during AO infusion on room air breathing are similar to those noted with oxygen breathing without the infusion. The mean arterial and venous oxygen tensions achieved during AO infusion on oxygen breathing approach values anticipated under hyperbaric conditions.
Although hemoglobin is essentially fully saturated at a
PO2 of 100 mm Hg, the
oxygen content of blood is nevertheless increased by 2 vol % when
the PO2 is increased to 600
mm Hg from normoxemic levels as a result of increased dissolution
of the gas.33 The oxygen delivery rate
should thereby be increased accordingly. As shown in the experimental
coronary model, hyperoxemic low flow at this
PO2 was unassociated with a
significant decrease in LVEF compared with that associated with
baseline physiological flow, in contrast to the
effects of low-flow normoxemic and hypoxemic flow. The lack of a
significant change in coronary sinus
PO2 with different levels of oxygen
in the perfusate suggests that oxygen extraction may have
increased with higher arterial oxygen levels. Our results
are consistent with those of Cason et
al,34 who demonstrated that hyperoxemic
flow (mean PO2=511±70 mm
Hg), compared with normoxemic flow at the same low rate in a porcine
coronary artery model, is associated with improved left
ventricular systolic shortening, increased
endocardial blood flow, and a reduction in lactate production.
The same group has also shown that hyperoxemia exerts a similar
increase in left ventricular systolic shortening
compared with normoxemia in a porcine model of myocardial
stunning.35
Experimental evidence suggests that hyperoxemia may also be beneficial for the treatment of reperfusion injury of the myocardium.36–38 Although oxygen-derived free radicals are generated on normoxemic reperfusion,39 the efficacy of free radical scavengers and antioxidants in reducing infarct size is controversial.40 An increase in capillary density was noted experimentally with the use of hyperbaric oxygen therapy during reperfusion in striated muscle,41 and Zamboni et al42 demonstrated that hyperbaric oxygen therapy during the first 1 to 2 hours of reperfusion of the rat gracilis muscle after 4 hours of ischemia inhibited neutrophil adherence to postcapillary venules. Recently, it was shown that hyperbaric oxygen impairs cGMP synthesis by activated neutrophils, so that B2 integrin–dependent adherence is inhibited.43 Rather than increasing oxygen free radical production, hyperbaric oxygen therapy has been shown to enhance a biochemical pathway for quenching lipid peroxide radicals.44
In tests of hypotheses related to the utility of hyperoxemia in the treatment of ischemic syndromes, infusion of AO to control regional arterial oxygen tension may offer a number of advantages over the use of cumbersome and expensive hyperbaric oxygen chambers. For example, hyperbaric oxygen exposures are typically limited to 90 min/d because of the risk of pulmonary oxygen toxicity. Although oxygen toxicity thresholds (duration times level) of tissues perfused with hyperoxemic blood from a regional AO infusion require study, pulmonary oxygen toxicity is not a limiting factor, and intermittent treatment should be simple to implement. In addition, the effect of hyperoxemic perfusion of a target tissue can now be studied independently of superimposed peripheral hemodynamic effects of systemic hyperoxemia produced by hyperbaric oxygen exposure. For example, the oxygen cost of contractility is increased in left ventricular dysfunction45 and stunning46; whether an increase in local oxygen delivery would be associated with an increase in oxygen extraction and improvement in function could be addressed with a regional AO infusion.
The maximum level of hyperoxemia that is achievable with an AO
infusion, below the threshold for microbubble formation, has not been
defined. As noted previously, arterial
PO2 of 2 bar have been achieved in
a prior pilot study, but microbubble formation occurred in some animals
in an unpredictable manner. Lower levels of hyperoxemia were therefore
used in the present work to identify potential adverse effects of
the infusion without superimposed problems that microbubbles would
present. Harvey et al47 noted that the
tensile strength (threshold for cavitation) of blood decompressed under
static conditions is high, on the order of 37 bar. Lee et
al48 also demonstrated high thresholds for
bubble nucleation in static, air-supersaturated blood experimentally on
decompression to atmospheric pressure. However, it is likely that under
dynamic, flowing conditions, the cavitation threshold in blood is much
lower than these values.29 Experience with
decompression sickness in humans provides only indirect information
regarding cavitation thresholds in blood, because the source of bubble
emboli in gas-supersaturated tissues is ambiguous and includes ruptured
alveoli and perivascular tissues, such as connective tissue under
simultaneous mechanical
tension.47 In vitro, microbubble formation
occurred during AO infusion in dog anoxic blood during rapid mixing at
a mean PO2 of 830 mm
Hg.18 This value is similar to that
observed for the bubble nucleation threshold associated with an
infusion of a dilute hydrogen peroxide solution into
blood.49 The primary reason that the latter
approach was abandoned clinically was the unavoidable formation of
methemoglobin.50 In the present study,
in contrast, no change in methemoglobin levels was noted after 2 hours
of AO infusion.
Study Limitations
Our primary goal in this study was to assess the feasibility of
the use of an AO infusion to correct hypoxemia and to produce
hyperoxemia. Although no adverse effects were noted, additional studies
will be required to ensure that more subtle adverse effects on blood
elements, plasma chemistries, and perfused tissues are not produced by
the infusion. In addition, the rate and level of dilution of AO, as
well as flow patterns of both blood and the AO effluent, that permit
effective oxygenation without microbubble formation
will require further study. It is likely that to precisely control an
AO infusion in a future clinical setting, continuous monitoring of the
infusate/blood mixture with an oxygen sensor and a microbubble detector
will be required. Finally, although pulmonary oxygen toxicity
is not a consideration with this new approach, the oxygen tolerance of
perfused normal and postischemic tissues as a function of
both the level of hyperoxemia and duration of exposure will require
study.
Conclusions
The results of our studies support the hypotheses that correction
of arterial hypoxemia and production of hyperoxemia
on a regional basis are achievable with an AO infusion. Specific
hypotheses regarding the effects of hyperoxemia on ischemic
tissue function and metabolism can now be addressed with
this catheter-based approach without concern for pulmonary
oxygen toxicity.
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Acknowledgments |
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This study was supported by grants from the National Institutes of Health (HL-56436) and from TherOx, Inc.
Received July 13, 1997; revision received September 3, 1997; accepted September 6, 1997.
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