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Ann Thorac Surg 1996;61:1631-1635
© 1996 The Society of Thoracic Surgeons

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Original Article: General Thoracic

Critical Importance of the First 10 Minutes of Lung Graft Reperfusion After Hypothermic Storage

Department of Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, United Kingdom

Accepted for publication February 17, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. We have shown previously that lung graft function can be improved by achieving reperfusion with stepwise increments of perfusion pressure over 60 minutes. This study aimed to establish whether similar benefit could be achieved with a shorter, simpler protocol and different storage conditions.

Methods. Rat lungs were flushed with University of Wisconsin or modified Euro-Collins solution and reperfused for 1 hour with blood from a support animal. Grafts were reperfused immediately or after storage at 4°C for 24 hours (University of Wisconsin solution) or 6 hours (Euro-Collins solution). Stored-graft reperfusion was initiated with a 0-, 5-, or 10-minute period during which reperfusion pressure was reduced by 50%.

Results. Stored grafts receiving 0 or 5 minutes of initial low-pressure reperfusion performed poorly, with reduced oxygenation and blood flow and elevated pulmonary artery pressure, airway pressure, and wet/dry weight ratio. In contrast, 10 minutes of initial 50%-pressure reperfusion yielded function comparable with that in controls with both storage conditions.

Conclusions. An initial 10-minute period of 50%-pressure reperfusion improves the function of stored rat lung grafts, whereas 5 minutes is insufficient.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The number of lung and heart-lung transplantation procedures performed increased steadily in the 1980s and early 1990s but now seems to have plateaued, and may even be declining [1]. Availability of donors continues to fall short of demand, and although prolonged lung preservation is possible in laboratory models, the incidence of early graft dysfunction in clinical practice has restricted storage times and therefore the geographic distribution of organs and donor-recipient matching. Early graft dysfunction with hypoxia and noncardiogenic pulmonary edema is a manifestation of ischemia-reperfusion injury. Changes in the graft during ischemia trigger a cascade of damaging events on reperfusion, mediated by production of free radicals, increased endothelial permeability, platelet aggregation, and neutrophil recruitment and activation [2]. This process may be attenuated by improved preservation techniques and interventions during reperfusion with, for example, free radical scavengers, leukocyte depletion, or agents that block neutrophil-endothelial interactions [3, 4].

We have shown previously that rat lung graft dysfunction can be ameliorated by controlling the initial reperfusion pressure [5]. Grafts were stored in University of Wisconsin (UW) solution for 24 hours at 4°C and reperfused in an isolated lung perfusion circuit using a support animal. Whereas grafts reperfused at physiologic pressure performed poorly, function was significantly improved when reperfusion was achieved with stepwise increments in pressure from 20% up to physiologic levels over a period of 60 minutes. The aim of the current study was to establish whether the same benefit could be achieved with a shorter, simpler protocol of controlled reperfusion, which might be more applicable to clinical practice. After defining such a protocol, we tested it in a second series of experiments to ascertain whether the beneficial effect was unique to 24-hour storage in UW solution. Grafts were stored this time for 6 hours at 4°C in modified Euro-Collins (EC) solution, a combination of storage conditions more relevant to current clinical lung transplantation.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Male Sprague-Dawley rats (Charles River Laboratories, Kent, UK) weighing 350 to 420 g were used throughout. All animals received humane care in compliance with the United Kingdom Government's Animals (Scientific Procedures) Act of 1986, and all procedures were carried out under terminal general anesthesia. Anesthesia was induced with halothane inhalation and maintained with intraperitoneal pentobarbitone sodium, 100 mg/kg. Animals and isolated grafts were ventilated using a Harvard rodent ventilator (Harvard Apparatus, Kent, UK).

Donor Procedure
Lung donors were anesthetized, intubated through a tracheostomy with a 16-gauge intravenous cannula, and ventilated with room air using 60 cycles/min, 10 mL/kg tidal volume, and 3 cm H₂O positive end-expiratory pressure. Methylprednisolone 30 mg/kg was given through the femoral vein 45 minutes before lung explantation. Median sternotomy was performed, the pleura and pericardium were opened, and the thymus was excised. A ligature was passed through the transverse sinus to encircle the aorta and pulmonary artery trunk. Heparin 500 U was given intravenously. The inferior vena cava was then clamped, the left atrial appendage was amputated, and the right ventricular outflow tract was opened. A primed, olive-tipped 20-gauge cannula was passed into the pulmonary artery trunk and tied with the previously placed ligature. The lungs were flushed through this cannula with perfusate precooled to 4°C and delivered by 25 cm H₂O hydrostatic pressure at a volume of 60 mL/kg.

Flush perfusates used were UW solution (DuPont Pharmaceuticals, Letchworth Garden City, UK) and EC solution (Fresenius AG, Bad Homburg, Germany) modified by the addition of 5 mmol/L magnesium sulfate. Lungs flushed with EC were pretreated with prostacyclin, given through the inferior vena cava at a rate of 20 ng•kg^-1•min^-1 for 10 minutes immediately before flushing. We also added prostacyclin 200 µg/L to the EC solution.

At the end of the flush procedure, the tracheal cannula was clamped with the lungs fully inflated, and the heart and lungs were excised en bloc. For storage, the block was submerged in the flush solution.

Support Animal
The support animals used during reperfusion were anesthetized and ventilated as described for lung donors and placed on a homeothermic warming blanket (Harvard Apparatus). Through a median sternotomy, mediastinal structures were exposed and the brachiocephalic artery was ligated. For connection to the reperfusion circuit, a 16-gauge intravenous cannula was passed through the right superior vena cava into the inferior vena cava through the right atrium, and an 18-gauge cannula was passed through the left superior vena cava into the right atrium.

Reperfusion
Before reperfusion, the left lung and postcaval lobe of the grafts were removed. A double lumen cannula was placed in the pulmonary artery. The graft was suspended in an insulated chamber and ventilated with room air using 30 cycles/min, 10 mL/kg tidal volume, and 3 cm H₂O positive end-expiratory pressure. Blood drawn from the inferior vena cava of the support animal was delivered by hydrostatic pressure into the pulmonary artery of the graft. Graft effluent drained through the opened left atrium and was collected and returned to the right atrium of the support animal by a pump (Variable Speed Peristaltic Pump; Harvard Apparatus). Thus, the support animal was able to supply deoxygenated blood continuously to the graft. The circuit tubing and reperfusion chamber were water-lagged to maintain blood temperature at 38°C. Blood obtained from a separate animal was used to prime the circuit and to replace losses together with 0.9% saline solution. Any support animal with acidosis occurring during reperfusion was treated with sodium bicarbonate to maintain a base excess of ±2.

The circuit was designed such that the vertical distance between the graft and the support animal generated hydrostatic reperfusion pressure equivalent to the physiologic pulmonary artery pressure of these rats (18 to 20 mm Hg), as measured by us and by others [6]. Reperfusion pressure was reduced to 50% by reducing the vertical distance proportionately.

Protocol
Twenty-eight lung grafts were flushed with UW solution. Group UW-A grafts (n = 7) were reperfused immediately after explantation at physiologic pressure for baseline data. The remainder were stored in UW solution for 24 hours at 4°C and then randomly allocated to one of three reperfusion protocols. In group UW-B (n = 6), physiologic-pressure reperfusion (PPR) was used throughout. In group UW-C (n = 7), the initial 5 minutes of reperfusion were conducted with the perfusion pressure reduced by half (50% PPR), and reverting subsequently to standard PPR. Grafts in group UW-D (n = 8) were reperfused with an initial 10-minute period of 50% PPR. All grafts were reperfused for a total of 60 minutes.

Subsequently, another 18 lung grafts were flushed, this time with modified EC solution. Group EC-A grafts (n = 6) were reperfused immediately and EC-B grafts (n = 6) after 6-hour 4°C storage, all using standard PPR. Grafts in group EC-C (n = 6) were also stored for 6 hours, but were reperfused with an initial 10-minute period of 50% PPR.

Measurements
Blood samples were taken from the reperfusion circuit proximal to the graft and from graft effluent at 5, 10, 15, and 20 minutes, and every 10 minutes thereafter, for gas tension and acid/base measurements. These allowed monitoring of the stability of the support animal, consistency of (de)oxygenation of afferent blood, and reoxygenation by the graft. An in-line ultrasonic flow probe (Transonic Systems, Ithaca, NY) measured graft blood flow, and the second lumen of the reperfusion cannula was connected to a transducer for measurement of pulmonary artery pressure (PAP). Flow and PAP were recorded continuously using a data acquisition package (Dataq Instruments, Akron, OH) and were subsequently analyzed for point measurements at 2.5-minute intervals. Another transducer gave graft peak airway pressure readings which, with fixed-volume ventilation, reflect changes in compliance. Lung tissue was weighed at the end of the reperfusion period and again after drying to constant weight at 120°C. Wet/dry weight ratio was calculated as (wet weight - dry weight)/dry weight.

Statistical Analysis
All data are expressed as mean ± standard error of the mean. Means were compared by analysis of variance. If differences were found, the Bonferroni post hoc test was used for parametric data and Dunn's test for nonparametric data; p values less than 0.05 were considered significant.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
All reperfusion experiments were conducted successfully for 1 hour. Support animals remained stable in terms of heart rate; state of filling of the inferior vena cava, heart, and pulmonary artery (assessed by visual inspection of the open chest); core temperature; and venous blood gas and pH measurements. Volume replacement and bicarbonate requirements did not vary significantly among groups. The oxygen tension (pO₂) of blood reperfusing the grafts was constant during the individual experiments as well as within and between groups. This stability is a consistent feature of the model and has been documented in more detail in previous studies [7, 8].

Reoxygenation
Grafts stored in UW solution for 24 hours and reperfused using either standard PPR or a 5-minute initial period of 50% PPR performed poorly compared with controls (Fig 1A). At 1 hour, effluent pO₂ (in mm Hg) was: group UW-A, 131 ± 2; group UW-B, 61 ± 9 (p < 0.001 compared with group UW-A); and group UW-C, 64 ± 11 (p < 0.001). In contrast, with an initial 10-minute period of 50% PPR (group UW-D), oxygen tensions were at control levels (pO₂, 138 ± 3 mm Hg at 1 hour; p = not significant). Similarly, after 6-hour storage in modified EC solution, significant protection against failure of gas exchange was afforded by 10 minutes of 50% PPR (see Fig 1B): pO₂ (mm Hg) at 1 hour in group EC-A was 135 ± 3; in group EC-B, 36 ± 6 (p < 0.001 versus group EC-A); and in group EC-C, 134 ± 5 (p = not significant).

View larger version (25K): [in this window] [in a new window]   Fig 1. . Partial pressure of oxygen (pO2) in graft effluent during 1 hour of reperfusion after flush ± storage with (A) University of Wisconsin solution and (B) modified Euro-Collins solution. Data are shown as mean ± standard error of the mean. (PPR = physiologic-pressure reperfusion; ***p < 0.001 versus control group.)

View larger version (33K): [in this window] [in a new window]   Fig 2. . Graft blood flow during 1 hour of reperfusion after flush ± storage with (A) University of Wisconsin solution and (B) modified Euro-Collins solution. Data are shown as mean ± standard error of the mean. (PPR = physiologic-pressure reperfusion; **p < 0.01, ***p < 0.001 versus control group.)

View larger version (28K): [in this window] [in a new window]   Fig 3. . Graft mean pulmonary artery pressure (PAP) during 1 hour of reperfusion after flush ± storage with (A) University of Wisconsin solution and (B) modified Euro-Collins solution. Data are shown as mean ± standard error of the mean. (PPR = physiologic-pressure reperfusion; **p < 0.01, ***p < 0.001 versus control group.)

Throughout the periods of 50% PPR, graft flows rose and PAP fell steadily. Comparison of 5- and 10-minute data using paired t tests showed that during this apparently crucial additional period of 50% PPR, there was a statistically significant increase in graft flow in groups UW-D (p < 0.01) and EC-C (p < 0.05) and a decrease in PAP in group EC-C (p < 0.05). Group UW-D also had a downward trend in PAP between 5 and 10 minutes, but this did not reach statistical significance.

Airway Pressure
Peak airway pressure (in mm Hg) was constant in the control groups, and at 1 hour it was 15.0 ± 0.3 in group UW-A and 14.6 ± 0.2 in group EC-A. It became significantly elevated in groups UW-B (33.0 ± 5.9 at 1 hour; p < 0.01 versus group UW-A), UW-C (29.1 ± 4.6; p < 0.05), and EC-B (45.0 ± 2.2; p < 0.001 versus group EC-A), reflecting decreased compliance, largely from edema formation. In contrast, peak airway pressure remained similar to that in controls after 10 minutes of initial 50% PPR in groups UW-D (14.8 ± 0.4 at 1 hour; p = not significant) and EC-C (14.3 ± 0.8; p = not significant).

Wet/Dry Weight Ratio
Control wet/dry weight ratios were 5.4 ± 0.4 in group UW-A and 4.3 ± 0.2 in group EC-A. Standard PPR and an initial 5 minutes of 50% PPR produced significant increases in weight gain: The ratio in group UW-B was 8.6 ± 0.7 (p < 0.01 versus group UW-A); in group UW-C, 9.2 ± 0.7 (p < 0.001); and in group EC-B, 9.7 ± 0.1 (p < 0.001 versus group EC-A). In contrast, an initial 10-minute period of 50% PPR prevented this weight gain: The wet/dry ratio in group UW-D was 5.9 ± 0.4 (p = not significant versus group UW-A); and in group EC-C, 5.5 ± 0.8 (p = not significant versus group EC-A).

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
This study has shown that reperfusion of stored rat lung grafts at physiologic pressure yields poor function with reduced reoxygenation, reduced blood flow, elevated PAP, elevated peak airway pressure, and significant weight gain. All of these changes are prevented by an initial 10-minute period of reperfusion at 50% physiologic pressure, whereas a 5-minute period is insufficient. The mechanism of this protective effect appears to be independent of the storage medium and the duration of ischemia, as it was operational whether storage was for 24 hours in UW solution or for 6 hours in modified EC solution.

Reduction of ischemia-reperfusion injury by controlled reperfusion is well recognized in cardiac and skeletal muscle, with the combined use of low pressure and modified initial reperfusate. The use of substrate-enriched "hot-shot" cardioplegia in cardiac operations is common. This has resulted from previous work in animal studies showing that controlled reperfusion of ischemic myocardium with total vented bypass and substrate-enriched blood cardioplegia attenuated reperfusion injury [9, 10]. Clinically, the use of substrate-enriched cardioplegia and controlled-pressure reperfusion in acute myocardial revascularization has been shown to improve immediate functional recovery [11]. The use of controlled pressure alone has also been investigated. In animal studies, initial reperfusion with normal blood but at reduced pressure for 20 minutes reduced postischemic myocardial damage [12], as did prevention of hyperemia [13]. Studies on controlled reperfusion of the acutely ischemic lower limb also have shown beneficial effects of initial reperfusion for a 30-minute period with reduced pressure and a formulated reperfusate [14].

The potential benefits of modification of the early phase of lung graft reperfusion are becoming apparent. In addition to our previous [5] and current findings, it has recently been reported that rabbit lungs stored in cold low-potassium dextran solution for 6 hours [15] or 30 hours [16] functioned better if reperfusion was for an initial 4-minute period with warm low-potassium dextran. In another study, rabbit lungs stored for 18 hours in modified EC solution functioned better when, for the first 10 minutes of reperfusion, blood was diluted to a hematocrit of 10% [17].

The mechanism by which controlled-pressure reperfusion exerts a protective effect in lung grafts is not yet known. It is possible that in our model, during ischemia or in the early phase of reperfusion, endothelial permeability was increased so that at physiologic reperfusion pressure, rapid edema formation led to irreversible damage. On the other hand, initial reduced-pressure reperfusion may have provided a window during which edema-forming hydrostatic pressure was low, while resumption of metabolic activity allowed recovery of endothelial barrier function sufficient for subsequent toleration of physiologic-pressure reperfusion.

There is indirect evidence that endothelial vasomotor dysfunction may have resolved during initial low-pressure reperfusion, as significant improvement of graft hemodynamic indices occurred during 50% PPR between 5 and 10 minutes in groups UW-D and EC-C. Critical recovery of endothelial production of vasodilating autocoids such as nitric oxide and prostacyclin may have occurred during this time. In addition to their vasoactive effects, these agents have a wide range of protective actions in ischemia-reperfusion injury [2].

The role of shear stress may also be important. Reperfusion of rat lungs after prolonged ischemia causes endothelial detachment [18], and lower shear stress with controlled reperfusion may be beneficial in this respect. The onset of shear stress stimulates expression of intercellular adhesion molecule-1 [19] and release of the cytokines interleukin-1 and interleukin-6 [20] by endothelial cells in vitro. On the other hand, shear stress has beneficial effects on endothelium, including increased release of prostacyclin and nitric oxide and decreased cell adhesion [21]. Indeed, it has been suggested that low flow and shear stress may be responsible for increased neutrophil-mediated ischemia-reperfusion injury in lungs [22]. However, the fact that controlled reperfusion is required for only 10 minutes suggests that its protective mechanism may not be related to neutrophil recruitment, as this tends to occur later in the course of lung reperfusion injury [23].

Our studies suggest that exposure of lung grafts to physiologic reperfusion pressure at transplantation may contribute to early dysfunction. Indeed, many recipients have preexisting pulmonary hypertension, so the graft may be subjected to even higher pressure. Controlled, low-pressure reperfusion for a relatively short period would be simple to implement and may benefit early graft function.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
This work was supported by a grant from the North West Regional Health Authority, UK.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr Hooper, Department of Cardiothoracic Surgery, Wythenshawe Hospital, Southmoor Rd, Manchester M23 9LT, United Kingdom.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Hosenpud JD, Novick RJ, Breen TJ, Keck B, Daily P. The registry of the International Society for Heart and Lung Transplantation: twelfth official report-1995. J Heart Lung Transplant 1995;14:805–15.[Medline]
2. Grace PA. Ischaemia-reperfusion injury. Br J Surg 1994;81:637–47.[Medline]
3. Novick RJ, Menkis AH, McKenzie FN. New trends in lung preservation: a collective review. J Heart Lung Transplant 1992;11:377–92.[Medline]
4. Steinberg JB, Mao HZ, Niles SD, Jutila MA, Kapelanski DP. Survival in lung reperfusion injury is improved by an antibody that binds and inhibits Land E-selectin. J Heart Lung Transplant 1994;13:306–18.[Medline]
5. Hopkinson DN, Bhabra MS, Odom NJ, Bridgewater BJM, van Doorn CA, Hooper TL. Controlled reperfusion of rat pulmonary grafts yields improved function after twenty-four hours' cold storage in University of Wisconsin solution. J Heart Lung Transplant 1996;15:283–90.[Medline]
6. Sato K, Webb S, Tucker A, et al. Factors influencing the idiopathic development of pulmonary hypertension in the fawn-hooded rat. Am Rev Respir Dis 1992;145:793–7.[Medline]
7. Hopkinson DN, Odom NJ, El Oakley RM, Au J, Hooper TL. A technique for studying the function of an isolated, perfused and ventilated lung in a rat model. Lab Animals 1995;29:96–101.[Abstract/Free Full Text]
8. Hopkinson DN, Odom NJ, Bridgewater BJM, Hooper TL. University of Wisconsin solution for lung graft preservation: which components are important? J Heart Lung Transplant 1994;13:990–7.[Medline]
9. Vinten-Johansen J, Buckberg GD, Okamoto F, Rosenkranz ER, Bugyi H, Leaf J. Studies of controlled reperfusion after ischemia. V. Superiority of surgical versus medical reperfusion after regional ischemia. J Thorac Cardiovasc Surg 1986;92:525–34.[Abstract]
10. Okamoto F, Allen BS, Buckberg GD, et al. Regional blood cardioplegic reperfusion during total vented bypass without thoracotomy: a new concept. J Thorac Cardiovasc Surg 1986;92:553–63.[Abstract]
11. Beyersdorf F, Sarai K, Maul FD, Wendt T, Satter P. Immediate functional benefits after controlled reperfusion during surgical revascularization for acute coronary occlusion. J Thorac Cardiovasc Surg 1991;102:856–66.[Abstract]
12. Okamoto F, Allen BS, Buckberg GD, Bugyi H, Leaf J. Studies of controlled reperfusion after ischemia. XIV. Reperfusion conditions: importance of ensuring gentle versus sudden reperfusion during relief of coronary occlusion. J Thorac Cardiovasc Surg 1986;92:613–20.[Abstract]
13. Peng CF, Murphy ML, Colwell K, Straub KD. Controlled versus hyperemic flow during reperfusion of jeopardized ischemic myocardium. Am Heart J 1989;117:515–22.[Medline]
14. Beyersdorf F. Protection of the ischemic skeletal muscle. Thorac Cardiovasc Surg 1991;39:19–28.[Medline]
15. Moriyasu K, McKeown PP, Novitsky D, Snow TR. Beneficial effect of initial warm crystalloid reperfusion in 6-hour lung preservation. J Heart Lung Transplant 1995;14:699–705.[Medline]
16. Moriyasu K, McKeown PP, Novitsky D, Snow TR. Preservation of competent rabbit lung function after 30 hours of storage with a low-potassium dextran solution. J Heart Lung Transplant 1995;14:75–9.[Medline]
17. Puskas JD, Oka T, Mayer E, et al. Hemodilution reduces early reperfusion injury in an ex vivo rabbit lung preservation model. Ann Thorac Surg 1994;57:731–5.[Abstract/Free Full Text]
18. Pickford MA, Green CJ, Sarathchandra P, Fryer PR. Ultrastructural changes in rat lungs after 48 h cold storage with and without reperfusion. Int J Exp Pathol 1990;71:513–28.[Medline]
19. Nagel T, Resnick N, Atkinson WJ, Dewey CF, Gimbrone MA. Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. J Clin Invest 1994;94:885–91.
20. Sterpetti AV, Cucina A, Morena AR, et al. Shear stress increases the release of interleukin-1 and interleukin-6 by aortic endothelial cells. Surgery 1993;114:911–4.[Medline]
21. Reinhart WH. Shear-dependence of endothelial functions. Experientia 1994;50:87–93.[Medline]
22. Seibert AF, Haynes J, Taylor A. Ischemia-reperfusion injury in the isolated rat lung. Role of flow and endogenous leukocytes. Am Rev Respir Dis 1993;147:270–5.[Medline]
23. Eppinger MJ, Jones ML, Deeb GM, Bolling SF, Ward PA. Pattern of injury and the role of neutrophils in reperfusion injury of rat lung. J Surg Res 1995;58:713–8.[Medline]

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				M. S. Bhabra, D. N. Hopkinson, T. E. Shaw, and T. L. Hooper ATTENUATION OF LUNG GRAFT REPERFUSION INJURY BY A NITRIC OXIDE DONOR J. Thorac. Cardiovasc. Surg., February 1, 1997; 113(2): 327 - 334. [Abstract] [Full Text]

				M. S. Bhabra, D. N. Hopkinson, T. E. Shaw, and T. L. Hooper Relative Importance of Prostaglandin/Cyclic Adenosine Monophosphate and Nitric Oxide/Cyclic Guanosine Monophosphate Pathways in Lung Preservation Ann. Thorac. Surg., November 1, 1996; 62(5): 1494 - 1499. [Abstract] [Full Text]

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