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Division of Cardiothoracic Surgery, Department of Surgery, and Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Jones, David R., Randy M. Becker, Steve C. Hoffmann, John J. Lemasters, and Thomas M. Egan. When does the lung
die? Kfc, cell
viability, and adenine nucleotide changes in the circulation-arrested rat lung. J. Appl. Physiol. 83(1):
247-252, 1997.
Lungs harvested from cadaveric
circulation-arrested donors may increase the donor pool for lung
transplantation. To determine the degree and time course of
ischemia-reperfusion injury, we evaluated the effect of
O2 ventilation on capillary
permeability [capillary filtration coefficient
(Kfc)],
cell viability, and total adenine nucleotide (TAN) levels in in situ
circulation-arrested rat lungs.
Kfc increased with increasing postmortem ischemic time
(r = 0.88). Lungs ventilated with
O2 1 h postmortem had similar
Kfc and
wet-to-dry ratios as controls. Nonventilated lungs had threefold
(P < 0.05) and sevenfold (P < 0.0001) increases in
Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in
all groups except for 30-min postmortem
O2-ventilated lungs. TAN levels
decreased with increasing ischemic time, particularly in nonventilated
lungs. Loss of adenine nucleotides correlated with increasing
Kfc values (r = 0.76). This study indicates that
lungs retrieved 1 h postmortem may have normal
Kfc with
preharvest O2 ventilation. The
relationship between
Kfc and TAN
suggests that vascular permeability may be related to lung TAN levels.
capillary filtration coefficient; cadaveric lung transplantation
INTRODUCTION LUNG TRANSPLANTATION has become an accepted and
effective treatment for a variety of end-stage pulmonary diseases. The
major impediment to more widespread application of this treatment
continues to be the shortage of satisfactory donors. A novel approach
to increase the donor pool would be to harvest lungs from
non-heart-beating cadaveric donors at intervals after death. The
hypothesis that lungs remain viable after cardiac arrest and are
suitable for transplantation has been the focus of investigation in our
laboratory (6, 7, 19).
The lung, unlike other solid organs, does not rely on perfusion for
cellular respiration. Respiration can occur directly across the
alveolar wall and is entirely passive. Although cessation of the
circulation with death leads to ischemia and cell death in other
organs, successful cell culture of lungs retrieved from morgue
specimens implies that lung tissue may remain viable long after death
of the organism (12). We previously showed 90% parenchymal cell
viability in rat lungs ventilated with
O2 4 h postmortem (3). In
addition, we demonstrated preservation of ultrastructure (1) and a
marked attenuation in the time-dependent decrement of lung high-energy
phosphate stores in O2-ventilated
cadaveric rat lung (4). These studies all attest that the lung is
viable for intervals after circulatory arrest.
Despite improved preservation techniques, the ischemia-reperfusion (IR)
insult to the transplanted lung remains a significant problem in the
early postoperative period. The ischemia-induced hypoxia results in
increased pulmonary endothelial cell permeability, which has been shown
to be related not only to the absolute level of
O2 deprivation but also to the
duration of ischemia (15). Although we demonstrated postmortem
pulmonary parenchymal cell viability before reperfusion, little is
known about the integrity of the pulmonary endothelial cell surface and
viability of the pulmonary parenchymal cell after reperfusion in the
postmortem lung.
The present study was designed to determine the degree and time course
of IR-induced microvascular injury as measured by the capillary
filtration coefficient
(Kfc) in in
situ circulation-arrested cadaveric rat lungs. In addition, we sought
to investigate the relationship between
O2 ventilation and
Kfc, pulmonary
vasculature hemodynamics, parenchymal cell viability, and adenine
nucleotide levels in the cadaveric rat lung.
METHODS Isolated perfused lung. Male
Sprague-Dawley rats weighing 250-450 g were anesthetized
intraperitoneally with pentobarbital sodium (20 mg/kg) (Abbott
Laboratories, Chicago, IL). A small laparotomy incision was made, and
600 U of heparin (Elkins-Sinn, Cherry Hill, NJ) were injected
intrahepatically under direct vision. The trachea was cannulated. The
rat was euthanized with an intrahepatic injection of pentobarbital
sodium (30 mg/kg). Cardiac arrest occurred within 1 min, documented by
observation of cardiac motion transmitted through the diaphragm and by
palpation. The laparotomy incision was closed with staples (Appose,
Davis and Geck, Danbury, CT). The rat was either ventilated (Harvard
rodent ventilator model 683; Harvard Apparatus, Millis, MA) with 100%
O2 at 60 breaths/min, a tidal
volume of 4 ml, and a positive end-expiratory pressure of 2 cmH2O or not ventilated. The
heart-lung block was left in situ in an effort to simulate the
cadaveric donor as closely as possible.
After varying intervals following death, a median sternotomy was
performed, the main pulmonary artery was cannulated through a right
ventriculotomy, and the left atrium was cannulated via a left
ventriculotomy. The catheters, flared at the tip, were sutured in
place. The heart, lungs, and mediastinal structures were removed en
bloc and suspended from a force-displacement transducer (model FT03,
Grass Instruments, Quincy, MA) into a humidified chamber to monitor
weight changes. The lungs were ventilated with 5%
CO2-20%
O2-75%
N2 at the ventilator settings
described above. The lungs were perfused with a peristaltic pump
(Minipuls 3, Gilson Medical Electronics, Middleton, WI) at a constant
flow of 0.03 ml/g body wt. The perfusate was Earle's balanced salt
solution [containing (in mmol) 2.4 CaCl2 · 2H2O,
0.4 MgSO4 (anhydrous), 5.4 KCl,
116 NaCl, 0.88 NaH2PO4
(anhydrous), 5.5 D-glucose, and 0.3 phenol red] containing O.21%
NaHCO3 and 4% bovine serum
albumin (Sigma Chemical, St. Louis, MO). The initial 75 ml of
perfusate, which contain residual red blood cells and plasma, were
discarded. An additional 40 ml of perfusate placed in a water-jacketed
reservoir were used for recirculation. The perfusate temperature was
maintained between 35 and 38.5°C, and the perfusate pH was
continuously monitored with a pH probe (Accumet; Fisher Scientific,
Pittsburgh, PA) placed in the venous reservoir. The pH was maintained
near 7.40 by adding dilute HCl or
NaHCO3 as necessary.
Pressure transducers (Cope Laboratories, Lakewood, CO) were positioned
at the hila of the lungs, zeroed to atmospheric pressure, and
calibrated with a mercury manometer. Pulmonary arterial (Ppa) and
pulmonary venous (Ppv) pressures were measured continuously. In
addition, peak inspiratory airway pressure (Paw) was continuously measured by positioning a T-tube on the inspiratory limb of the respiration plumbing. Peak inspiratory pressure was adjusted to ~7.0
mmHg for the control group, since previous studies have shown that
pressures <8.0 mmHg permitted adequate ventilation without altering
transvascular fluid flux (13). Zone 3 conditions (arterial > venous > alveolar pressures) were maintained throughout all experiments. All
pressure measurements and changes in weight gain were amplified
(Hewlett-Packard 8805D, Mountain View, CA) and then analyzed with a
special computer software package developed for our laboratory. Data
were recorded and displayed on a Macintosh II Fx computer.
Measurement of pulmonary capillary pressure
(Ppc). Ppc was estimated by using the double-occlusion
technique as described by Townsley (18). Simultaneous occlusion of
arterial and venous catheters results in equilibration of Ppa and Ppv
to the same pressure. This equilibration equals the Ppc and also
reflects the capillary pressure when the lung is not isogravimetric.
The pulmonary arterial (Ra) and venous (Rv) resistances were calculated from the following equations
where
is flow, and
Wt/t). The initial 3- to 5-min period of weight gain represents vascular distention and
recruitment and is not a reflection of capillary permeability. The
Wt/t between
minutes 6 and
15 represents increased transvascular
fluid flux secondary to increased capillary permeability. This later
Wt/t was analyzed by
using linear regression of the log10 
weight changes per
minute. The initial rate of weight gain was calculated by extrapolation
of Wt/t to
time 0.
The Starling equation describes the role of
Kfc in
transvascular fluid flux (14)
![<IT>J</IT><SUB>v</SUB> = <IT>K</IT><SUB>fc</SUB> [(Pc − Pi) − &sfgr; (&Pgr;<SUB>c</SUB> − &Pgr;<SUB>i</SUB>)]](/content/vol83/issue1/fulltext/247/img003.gif)
|
c and
i are osmotic pressures in the
capillary and interstitium, respectively; and 
is the osmotic
reflection coefficient. At the extrapolated time
0, both Pc and
Jv are elevated
to new steady states before the remaining factors can be
affected. Therefore, Kfc can be
calculated by using the equation
|
Wt/t at
time 0 by the change in Ppc that
occurred after Ppv elevation. It was normalized using baseline wet lung
weight and expressed as
ml · min
1 · cmH2O1 · 100 g lung tissue1.
Wet-to-dry (W/D) weight ratios. At the
completion of the experiment, the upper lobe of the right lung was
excised and immediately weighed. It was then dried in a 60°C oven
for 48 h and reweighed.
Lung parenchymal cell viability. After
excision of the right upper lobe, the right hilum was suture ligated.
Right lung pieces were flash-frozen in liquid nitrogen and stored at
70°C. Thirty milliliters of a 500 mM trypan blue solution
(Sigma Chemical), dissolved in Krebs-Heinseleit buffer (pH 7.4), were
infused into the left pulmonary artery via the existing catheter.
Trypan blue stains the nuclei of nonviable cells (10). The infusion
reservoir was positioned 30 cm above the heart. After infusion of the
trypan blue, 30 ml of fixative consisting of 2% gluteraldehyde and 2% paraformaldehyde in 0.1 M Sorenson's buffer were infused from the same
reservoir. During both infusions, mechanical ventilation with 100%
O2 was performed. The left lung
was then excised, placed in the same fixative, and stored at 4°C.
The left lung tissue was prepared for histological analysis by using
standard techniques. Briefly, the tissue was dehydrated in ethanol,
washed in xylene, and embedded in paraffin. Five-micrometer sections
were cut, mounted on slides, and counterstained with eosin only.
Cell viability was determined microscopically (Nikon, Melville, NY)
using ×1,000 magnification with oil immersion and an ocular grid.
The microscopist was blinded to the experimental group analyzed. Twenty-five parenchymal cell nuclei were identified in each quadrant and recorded as either viable (pink) or nonviable (blue). Each slide
was counted twice at different intervals. If a >10% difference existed between counts, a third and final count was performed. Lung
parenchymal cell viability was reported as the percentage of viable
cells.
High-performance liquid chromatography
(HPLC). Tissue samples previously retrieved from the
right lung for HPLC were pulverized by using a liquid nitrogen-cooled
Bessman pulverizer and then homogenized with ice-cold 0.6 N perchloric
acid (2-8 ml/g tissue) using a tissue tearer (Biospec Products,
Bartlesville, OK) at 30,000 revolutions/min (rpm) for 30 s. After
centrifugation for 2 min at 10,000 rpm, the supernatant was removed and
neutralized with cold 1 M potassium phosphate dibasic (pH 12) to
achieve a pH of 6.8. The supernatant was separated from precipitated
salt by repeat centrifugation for 2 min at 10,000 rpm. The remaining solution was passed through a 0.45-mm acrodisc filter.
ATP, ADP, AMP, xanthine, and hypoxanthine concentrations were
determined by HPLC using an LKB Bromma apparatus (LKB-Produkter, Bromma, Sweden). A partisil 10 SAX column (Whatman, Clifton, NJ) in
0.25 potassium phosphate monobasic (pH 6.5) at a flow rate of 1.5 ml/min was used to separate and quantify ATP and ADP levels. An EQC 5u
S C18 column (Whatman) in 0.25 M
ammonium phosphate monobasic (pH 4.5) at a flow rate of 2.0 ml/min was
used to measure AMP, xanthine, and hypoxanthine. For each assay,
50-100 ml of solution were injected into the HPLC system.
Chromatograms were analyzed on an IBM 486 DX 33-MHz computer with Peak
Simple software.
Standard curves were made by performing serial dilutions for ATP, ADP,
AMP, xanthine, and hypoxanthine (Sigma Chemical).
Specific protocol. Forty-eight pairs
of lungs were divided into eight groups
(n = 6 lungs/group):
group I, controls, retrieval immediately after death; group
II, retrieval 30 min postmortem and
O2 ventilation;
group III, retrieval 30 min postmortem
and no ventilation; group IV,
retrieval 60 min postmortem and O2
ventilation; group V, retrieval 60 min
postmortem and no ventilation; group VI, retrieval 120 min postmortem and
O2 ventilation;
group VII, retrieval 120 min
postmortem and no ventilation; and group
VIII, retrieval 240 min postmortem and
O2 ventilation. Control lungs were
extirpated immediately and reperfused within 5 min of death. All lungs
were allowed to equilibrate for 15-20 min to achieve an
isogravimetric state. Lungs that could not reach an isogravimetric state were discarded, and the experiment was repeated. During equilibration, the Ppa, Ppv, and Paw were measured and recorded every
minute. After equilibration, the Ppc was obtained, and the Kfc was measured.
The left lung was then perfused with trypan blue to determine cell
viability, and portions of the right lungs were frozen or weighed to
calculate the W/D ratio as described above.
Statistics. All results are expressed
as means ± SE. Comparisons among groups were made using analysis of
variance with Fisher's post hoc test for multiple comparisons.
Significance was determined to be present when
P < 0.05. Linear correlations were
obtained using Pearson's correlation coefficient.
RESULTS
The number of lungs unable to achieve isogravimetric state for each group was as follows: group I, 1; group II, 2; group III, 0; group IV, 0; group V, 2; group VI, 3; group VII, 3; and group VIII, 4.
Kfc. Changes in microvascular permeability as measured by Kfc are shown in Table 1. In nonventilated lungs, a marked increase in pulmonary microvascular permeability occurred as the postmortem ischemic time increased (r = 0.96) (Fig. 1). In lungs ventilated with O2, Kfc did not increase significantly compared with the control group for up to 60 min postmortem. In contrast, in nonventilated rats, the Kfc increased threefold after 30 min (P = 0.05) and sevenfold after 60 min (P = 0.0001) postmortem. After 120 min of postmortem time, the Kfc increased despite O2 ventilation. Attempts to evaluate Kfc after 240 min postmortem in nonventilated lungs were unsuccessful because the lungs failed to reach an isogravimetric state and had near-instantaneous pulmonary edema on reperfusion. However, Kfc could be assessed in O2-ventilated lungs 240 min postmortem (Fig. 1).
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W/D ratios. As the pulmonary microvascular permeability increased, lung weight gain increased, as measured by the W/D weight ratio (Table 1). The W/D ratio increased after 30 min postmortem ischemia for both the O2-ventilated and nonventilated groups. The W/D ratio was significantly less with O2 ventilation after 60 min compared with the 60- and 120-min nonventilated groups (P < 0.02). Kfc correlated with W/D ratio (r = 0.91) for all groups (Fig. 2).
Viability. Pulmonary parenchymal cell viability was determined after IR by using the trypan blue exclusion technique. The percentage of viable cells for each group is shown in Table 1. All groups had significantly decreased viability compared with control lungs except the 30-min postmortem ischemia group ventilated with O2. Viability correlated with Kfc and postmortem time in the O2-ventilated and nonventilated groups (Fig. 3).
Hemodynamics. Hemodynamic data are shown in Table 2. There were no significant differences among groups with respect to the Ppa or Ppv. Peak Paw was significantly increased in the 240-min postmortem ischemic group.
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DISCUSSION
The duration of postmortem ischemic time whereby lung function remains acceptable for transplantation is unknown. Identification of this time range and modifications in preservation techniques that could potentially increase the time are mandatory if transplantation of lungs from circulation-arrested donors is to become a reality. Previous studies from this laboratory have shown preserved parenchymal cell viability in adenine nucleotide levels in cadaveric rat lungs retrieved up to 12 h postmortem (3). This study was designed to evaluate viability and adenine nucleotide levels, as well as lung function, as measured by the capillary permeability coefficient after reperfusion.
The model used in this study is different from other isolated perfused rat lung models. Lungs were left in situ after the animal was euthanized, instead of the usual protocol of harvesting, perfusing, and then making the lungs ischemic. This model most closely resembles the clinical scenario of the circulation-arrested donor, which is of interest to us.
The degree of capillary permeability, as measured by Kfc, and the W/D ratio increased in all groups compared with controls. Interestingly, ischemic lungs ventilated with O2 had similar Kfc values and W/D ratios compared with the control group up to 60 min postmortem. Lungs reperfused after 120 min of ischemia had similar Kfc values and W/D ratios, regardless of preharvest ventilation. O2 ventilation did allow measurement of Kfc in lungs with postmortem ischemic time interval of 4 h, although the Kfc and W/D ratio were significantly increased compared with controls. This suggests a beneficial effect of O2 ventilation on the capillary permeability of the reperfused lungs. We have shown a similar benefit in O2-ventilated cadaveric lungs transplanted in dogs, as measured by improved gas exchange and recipient survival (19).
Although there is considerable evidence that reduced O2-derived species are responsible for oxidative injury to tissues, the degree of damage necessary to cause irreversible lung injury is unknown. Ayene et al. (2) have demonstrated increased oxidative stress as measured by lipid peroxidation in IR rat lungs ventilated with 100% O2. Unfortunately, no correlation was made between the increased lung oxidized protein levels and actual lung function. Haniuda et al. (9) have shown that lung function, as measured by Kfc, is not influenced by differences in the inspired O2 fraction during ischemic intervals up to 8 h. We have shown that O2 ventilation of cadaver dog lungs for 4 h before retrieval leads to improved lung function in recipients compared with lung function in recipients of nonventilated lungs (19). In addition, O2 ventilation of cadaveric rat lung resulted in improved viability compared with N2 ventilation or no ventilation (4).
In general, lung viability was decreased in lungs subjected to an ischemic period before perfusion (except 30-min O2-ventilated lungs, which did not differ from controls). Preharvest O2 ventilation did not increase the percentage of viable parenchymal cells compared with nonventilated lungs. This finding is contrasted by lung viability studies before reperfusion in the cadaveric rat lung. Prior studies have found that O2 delivery to the ischemic airway, rather than mechanical ventilation per se, was the critical factor in delaying cell death in nonperfused lungs (3). Approximately 20% more lung cells were viable before reperfusion than what we found after reperfusion for each postmortem ischemic time interval. Therefore, IR appears to decrease cell viability in this model, compared with viability in ischemic but nonreperfused lungs. Additionally, the beneficial effect of preharvest O2 ventilation on cell viability could not be demonstrated after lungs were reperfused.
This study shows a strong correlation between cell viability and microvascular capillary permeability (Kfc). This relationship was more apparent in O2-ventilated lungs. Realizing that lungs with high Kfc values will have a poorer gas exchange, it was particularly interesting to find a strong relationship between Kfc and cell viability. This implies that if lung parenchymal cell viability could be ascertained noninvasively preharvest, one would have an idea of the suitability of the lungs for transplant and what their immediate posttransplant lung function would be.
Tissue TAN levels decrease at different rates, depending on the organ. For example, TAN levels in rat liver decreased >75% after 2 h of ischemia (11) and >65% in mouse kidney after 2 h of ischemia (20). We have shown that TAN levels in nonventilated rat lung decreased 66% from baseline at 2 h postmortem. By comparison, O2 ventilation of rat lungs after 2 h of ischemia decreased TAN levels by 32% (4). In the present study, we found no difference in TAN levels between ventilated and nonventilated lungs. This suggests that TAN levels after reperfusion correlate better with length of postmortem ischemic time than with preharvest ventilation status. Alternatively, TAN levels may be somewhat restored by reperfusion with Earle's solution.
The present study shows a clear relationship between
Kfc, cell
viability, and adenine nucleotide levels in the IR rat lung. Whereas
previous studies from our laboratory suggested a benefit from
preharvest O2 ventilation in
circulation-arrested cadavers with respect to cell viability and
adenine nucleotide levels, this benefit is not as apparent after the
lungs are reperfused. O2
ventilation resulted in a significantly decreased
Kfc in lungs ventilated up to 1 h postmortem and allowed for
Kfc assessment in
lungs retrieved 4 h postmortem. Failure of the
Kfc to remain decreased after 60 min postmortem ischemia may be related to decreased cell viability and/or increased adenine nucleotide breakdown. Other possible explanations for this finding that were not explored in
this study include the sodium, potassium, and calcium fluxes between
the cell and the interstitium. Finally, alterations in the endothelial
cell cytoskeleton may affect capillary permeability; however, it is
unclear what length of ischemic time interval is necessary to result in
contraction of the actomyosin fibrils in the cell, which results in
this increased permeability. Seibert et al. (17) have suggested that
compounds that increase adenosine 3
,5-cyclic
monophosphate can reverse increased capillary permeability, presumably
through an adenosine 3,5-cyclic monophosphate-dependent endothelial cell relaxation.
In conclusion, this modification of traditional IR rat lung models has allowed us to further evaluate our hypothesis that lungs retrieved from circulation-arrested donors may be suitable for transplantation. This experimental design evaluates the acute effects of the postmortem ischemic time and ventilation on Kfc, cell viability, and adenine nucleotide levels. It does not address whether these observations are irreversible or constant over time, because our reperfusion time period was only ~45 min. A recent study suggests that the increase in permeability may be transient, even in lungs retrieved 4 h after death. Using a canine double-lung transplant model, we showed improvement in alveolar-to-arterial gradient and reduction in extravascular lung water over an 8-h period following lung transplant from O2-ventilated cadaver dogs (16). To investigate the time course of changes in permeability and gas-exchange characteristics, we plan to perform rat lung allograft transplantation with lungs retrieved from cadavers at intervals after death. These studies will further elucidate our understanding of lungs retrieved after death, perhaps culminating in the use of circulation-arrested donor lungs for lung transplantation.
ACKNOWLEDGEMENTS
We express appreciation to Robert T. Currin and Kimberlie Burns for their excellent technical assistance and to Betsy L. Mann for editorial assistance in the preparation of the manuscript. We also thank Dr. Pavel L. Khimenko and Dr. Aubrey E. Taylor for their technical support.
FOOTNOTES
Address for reprint requests: D. R. Jones, 108 Burnett-Womack Bldg., CB 7065, Chapel Hill, NC 27599-7065.
Received 23 December 1996; accepted in final form 14 March 1997.
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 S. Takashima, G. Koukoulis, H. Inokawa, M. Sevala, and T. M. Egan Inhaled nitric oxide reduces ischemia-reperfusion injury in rat lungs from non-heart-beating donors J. Thorac. Cardiovasc. Surg., July 1, 2006; 132(1): 132 - 139. [Abstract] [Full Text] [PDF]
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T. M. Egan, J. A. Haithcock, W. A. Nicotra, G. Koukoulis, H. Inokawa, M. Sevala, P. L. Molina, W. K. Funkhouser, and B. J. Mattice Ex Vivo Evaluation of Human Lungs for Transplant Suitability Ann. Thorac. Surg., April 1, 2006; 81(4): 1205 - 1213. [Abstract] [Full Text] [PDF]
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 Y.-W. Chen, K. C. Hwang, C.-C. Yen, and Y.-L. Lai Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R21 - R26. [Abstract] [Full Text] [PDF]
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T. M. Egan, Y. Thomas, D. Gibson, W. Funkhouser, P. Ciriaco, A. Kiser, J. Sadoff, M. Bleiweis, and C. E. Davis Trigger for intercellular adhesion molecule-1 expression in rat lungs transplanted from non-heart-beating donors Ann. Thorac. Surg., March 1, 2004; 77(3): 1048 - 1055. [Abstract] [Full Text] [PDF]
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R. Aguilo, E. Serra, B. Togores, A. de la Pena, C. Santos, and A. G. N. Agusti Long-term (72 hours) preservation of rat lungs J. Thorac. Cardiovasc. Surg., April 1, 2003; 125(4): 907 - 912. [Abstract] [Full Text] [PDF]
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A. C. Kiser, P. Ciriaco, S. C. Hoffmann, and T. M. Egan Lung retrieval from non-heart beating cadavers with the use of a rat lung transplant model J. Thorac. Cardiovasc. Surg., July 1, 2001; 122(1): 18 - 23. [Abstract] [Full Text] [PDF]
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 S. C. HOFFMANN, M. S. BLEIWEIS, D. R. JONES, H. C. PAIK, P. CIRIACO, and T. M. EGAN Maintenance of cAMP in Non-Heart-Beating Donor Lungs Reduces Ischemia-Reperfusion Injury Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1642 - 1647. [Abstract] [Full Text] [PDF]
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T. M. Egan Non-heart-beating lung donors: yes or NO? Ann. Thorac. Surg., November 1, 2000; 70(5): 1451 - 1452. [Full Text] [PDF]
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M. S. Bleiweis, D. R. Jones, S. C. Hoffmann, R. M. Becker, and T. M. Egan Reduced ischemia-reperfusion injury with rolipram in rat cadaver lung donors: effect of cyclic adenosine monophosphate Ann. Thorac. Surg., January 1, 1999; 67(1): 194 - 199. [Abstract] [Full Text] [PDF]
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