Extended hypothermic heart-lung preservation system for cardiopulmonary preservation with retrograde coronary sinus perfusion and lung immersion

One major restriction of clinical heart-lung transplantation has been the inability to provide extended hypothermic organ preservation. We examined whether core-cooling, retrograde heart perfusion and lung immersion could provide adequate cardiopulmonary preservation. Hence, donor dogs were placed on cardiopulmonary bypass, and rapidly cooled to 15 degrees C. Then heterotopic heart unilateral left lung transplantations were performed. In control group I (n = 5), hearts and lungs were harvested following core-cooling and cardioplegic arrest, and transplanted immediately. In experimental group II (n = 5), heart-lung blocks were similarly excised but stored at 4 degrees C for 12 hours and then transplanted. During preservation, the lungs were immersed in the extracellular solution. For the heart, non-recirculating retrograde coronary sinus perfusion was performed with oxygenated intracellular solution containing perfluorochemicals. Myocardial function determined by the ratio of end-systolic pressure to end-systolic dimension in the experimental group was similar to that in controls. Although pulmonary vascular resistance and extravascular lung water of the experimental group was higher than those in control group, arterial oxygenation was similar in both groups. Thus, extended heart-lung preservation with core-cooling, retrograde heart perfusion and lung immersion technique could be achieved for heart-lung transplantation.     

A no-flush, core-cooling technique for successful cardiopulmonary preservation in heart-lung transplantation

In order to determine whether a no-flush, core-cooling technique could provide extended heart-lung preservation, we placed donor calves on cardiopulmonary bypass and instituted rapid cooling to 15 degrees C during the continuous infusion of isoproterenol. The heart and lungs were harvested after the administration of a cardioplegic solution through the aortic root. In the control group (N = 5), heart and lungs were orthotopically allotransplanted immediately. In the preserved group (N = 5), heart and lungs were similarly excised but were stored in a normal saline bath at 4 degrees C for approximately 4 hours and then transplanted. Both groups received isoproterenol during reperfusion and were studied for 6 hours after implantation. A load independent analysis of myocardial function was done by determining with a sonomicrometer the ratio of the end-systolic pressure to the end-systolic dimension. Pulmonary preservation was evaluated by measurement of extravascular lung water with a double-indicator dilution method, arterial oxygenation on 100% inspired oxygen, and serial lung biopsies. Myocardial and pulmonary function after 4 hours of static preservation was found to be similar to controls. No-flush, core-cooling with cardiopulmonary bypass provides adequate cardiorespiratory function after acute bovine heart-lung allotransplantation. With the use of this technique, successful extended cold ischemic cardiopulmonary preservation for heart-lung transplantation may be achieved.     

Successful extended hypothermic cardiopulmonary preservation for heart-lung transplantation

The inability to obtain sufficiently extended hypothermic organ preservation is a major restriction on clinical heart-lung transplantation. We used core cooling, nonrecirculating retrograde heart perfusion, and lung immersion with liposomal recombinant human superoxide dismutase in an attempt to provide effective 12-hour cardiopulmonary preservation. Donor dogs supported by cardiopulmonary bypass were rapidly cooled to 15 degrees C with cardioplegic arrest, and heterotopic heart and unilateral left lung transplantations were performed. In control dogs (n = 7), hearts and lungs, harvested after core cooling and cardioplegic arrest, were transplanted with a total mean ischemic time of 88 +/- 5 minutes. In group II (n = 7), heart-lung blocks were similarly excised but preserved at 4 degrees C for 12 hours (756 +/- 30 minutes) and then transplanted. During preservation, the lungs were immersed in hyperosmolar extracellular solution. For the heart, retrograde coronary sinus perfusion was performed with intracellular solution containing perfluorochemicals at a temperature of 4 degrees C and a rate of 30 ml/hr for 12 hours. In group III (n = 7), donor organs were similarly excised and preserved for 12 hours (726 +/- 39 minutes), except that liposomal recombinant human superoxide dismutase was administered during harvest, preservation, and reperfusion. Myocardial function, assessed by the ratio of end-systolic pressure to end-systolic dimension, after the 12-hour preservation period in both experimental groups was similar to that of the control group 4 and 6 hours after transplantation. The mean arterial oxygen capacity of the transplanted left lung during ventilation with an inspired oxygen concentration of 40% was also similar in each group. In contrast, the 12-hour preservation of pulmonary function assessed by pulmonary vascular resistance, the accumulation of extravascular lung water, and histologic evidence of alveolar wall injury, interstitial edema, and perivascular hemorrhage were significantly impaired in the absence of liposal recombinant human superoxide dismutase. These findings suggest that successful extended cardiopulmonary preservation for heart-lung transplantation is possible with core cooling, nonrecirculating retrograde heart perfusion, and hypothermic lung immersion incorporating liposomal recombinant human superoxide dismutase.     

Single lung transplantation in primates. Modified Stanford heart-lung transplantation technique

Unilateral (left) lung allotransplantation was performed on six monkeys (Macaca fascicularis). Intravenous infusion of prostaglandin E-1 into the donor and cooling of the graft by perfusing the pulmonary artery with modified Euro-Collins solution were used for lung preservation. All six primates survived the operation, with good graft function, and were extubated after 4-6 hours. Mild pulmonary densities were found in all of them 3 days postoperatively. Two monkeys died, after 7 and 16 days, due to allograft failure. Autopsy in both cases showed bronchial stenosis, despite omental wrapping around the anastomosis. No other technical problems arose in the early postoperative course. It is concluded that prostaglandin E-1 pretreatment of the donor and single crystalloid flush of the donor lung improves the function of a single lung graft as well as that of a heart-lung transplant.     

Improved heart and lung preservation in a rat model

Abstract. We investigated the efficacy of four different preservation solutions in a heart-lung model in the rat. The heart and lungs of the donor were perfused under standardised conditions of temperature, pressure and flow. We studied 4 groups: group 1 received Stanford solution to heart and lung; group 2 received St. Thomas' solution to heart and Papworth solution to lung; group 3 received University of Wisconsin solution to heart and lung; and group 4 received University of Wisconsin solution to heart and Papworth solution to lung. Lung function assessed by arterial pO₂ at a standardised F_IO₂ was significantly better in groups 2 and 4 than in other groups. However, cardiac function as assessed by cardiac output, stroke work index and minute work index was significantly better in group 4 than in any other group. Overall, the combination of solutions in group 4 provided the most effective preservation in this model.     

Heart-Lung Transplantation for Irreversible Pulmonary Hypertension

Combined heart and lung transplantation was carried out in 17 patients at Stanford University between March, 1981, and December, 1983. The recipients were between 22 and 45 years old. All patients had end-stage pulmonary hypertension; 10 had Eisenmenger's syndrome and the remaining 7, primary pulmonary hypertension. Five patients died within the first few postoperative weeks. The remainder are well between four weeks and 33 months from operation.The immunosuppressive protocol has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin. Azathioprine also was given for the first two weeks and then was replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with high doses of methylprednisolone. Modifications of technique that have developed include the removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution.Rejection occurred in 6 of the 12 survivors. Infections developed in 9 patients, but only one resulted in a fatal outcome (Legionella). Thus, the results of clinical heart-lung transplantation have been considerably superior to clinical efforts in lung transplantation. It is suggested that the combined operation is preferable for the following reasons: (1) all diseased tissue is removed, thus eliminating recurrent infection and ventilation/perfusion disparity; (2) transplantation of the entire heart-lung block preserves coronary–bronchial vascular anastomoses and makes airway dehiscence less likely; and (3) to date, diagnosis of rejection by cardiac biopsy has appeared to be a satisfactory method of diagnosing and treating pulmonary rejection. Cardiopulmonary transplantation represents a viable therapeutic approach for patients with end-stage pulmonary hypertension with or without associated congenital heart disease.     

Improved heart and lung preservation in a rat model

We investigated the efficacy of four different preservation solutions in a heart-lung model in the rat. The heart and lungs of the donor were perfused under standardised conditions of temperature, pressure and flow. We studied 4 groups: group 1 received Stanford solution to heart and lung; group 2 received St. Thomas' solution to heart and Papworth solution to lung; group 3 received University of Wisconsin solution to heart and lung; and group 4 received University of Wisconsin solution to heart and Papworth solution to lung. Lung function assessed by arterial pO₂ at a standardised F₁O₂ was significantly better in groups 2 and 4 than in other groups. However, cardiac function as assessed by cardiac output, stroke work index and minute work index was significantly better in group 4 than in any other group. Overall, the combination of solutions in group 4 provided the most effective preservation in this model.     

The results of experimental study of six-hour heart-lung preservation by autoperfusion method--its evaluation of optimal conditions and lung function after preservation

Up to date, it has been reported that the maintenance of ideal function of the preserved lungs were much more difficult than that of the hearts in heart-lung preservation. In this communication the authors have reported the results of experimental study for optimal conditions for preserving better function of the lungs by autoperfusion method by means of heart-lung preparation using 43 dogs. In this study the conditions of the preservation were fixed as following: perfusing blood temperature 29 degrees C, blood flow 30 ml/kg/min., FiO2 30%, FiCO2 5%, tidal volume 15 ml/kg, ventilation rate 10/min., and PEEP 5 cmH2O. Glucose-Insulin-Potassium (0.03 gm., 0.05 U., 0.02 mEq/kg/hr. respectively) were administered continuously by an infusion pump. The results showed that extravascular lung water contents after 6 hours of preservation was 0.79 (mean) +/- 0.01 (SD), which was increased only 1% over than the control group: 0.78 +/- 0.01. There was no significant difference of static lung compliance in two groups: the preserved group was 0.47 +/- 0.02 ml/gm.cmH2O compared to 0.51 +/- 0.06 in the control group. These results suggest that the autoperfusion method on our preserving conditions seems to be very promising and very effective to keep much better condition of the lungs in heart-lung preservation.     

The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation.

We have previously demonstrated that a low-potassium dextran solution provides superior and more reliable preservation of lungs for 12 hours than that provided by the commonly used Euro-Collins solution. This study was designed to examine the individual contributions of dextran 40 and a low (extracellular) potassium concentration to lung preservation. In a randomized, blinded study using an in vivo canine single-lung transplant model, lungs preserved with low-potassium dextran solution (K+, 4 mmol/L; dextran 40, 20 gm/L) were compared to lungs preserved with low-potassium, no-dextran solution (K+, 4 mmol/L) and high-potassium dextran solution (K+, 123 mmol/L; dextran 40, 20 gm/L). The lungs were assessed immediately and 3 days after transplantation. The low-potassium dextran solution provided excellent immediate pulmonary function with little variability (arterial oxygen tension, 519 +/- 12 mm Hg, measured on the transplanted lung alone, inspired oxygen fraction = 1.0, n = 6). Removing the dextran 40 from the flush solution (low-potassium group) led to a significant deterioration in pulmonary function (arterial oxygen tension, 243 +/- 78 mm Hg, n = 6, p less than 0.01). The high-potassium dextran solution provided extremely poor preservation (arterial oxygen tension, 176 +/- 79 mm Hg; n = 6; p less than 0.01). Two animals in this group died within 6 hours of operation. Viability of the transplanted bronchus was significantly improved with the two solutions containing dextran 40. These results indicate that dextran 40 and low potassium concentration both contribute significantly to the uniformly excellent 12-hour lung preservation seen with the low-potassium dextran solution.     

Successful extended cardiopulmonary preservation in the autoperfused working heart-lung preparation

Myocardial and pulmonary preservation can be prolonged in the autoperfused working heart-lung (AWHL) preparation by metabolic substrate enhancement. However, uncontrolled pulmonary hypertension following denervation may result in extensive lung injury and occasional early failure of the preparation. To determine whether cardiopulmonary preservation could be reliably extended without development of pulmonary hypertension, six heart-lung blocks were harvested from calves, placed in a normothermic AWHL circuit, and studied. Continuous infusions of isoproterenol and dextrose/insulin were administered for the duration of the preparation. Thirteen heart-lung preparations received neither isoproterenol nor metabolic substrate and served as controls. Myocardial function was assessed by sonomicrometric techniques and pulmonary preservation was evaluated by extravascular lung water, arterial oxygenation on 100% inspired oxygen, static lung compliance, and pulmonary vascular resistance. Pulmonary hypertension developed in the control group and these animals did not survive beyond 7.5 hours. The addition of isoproterenol and metabolic substrate increased organ survival from 4.8 +/- 0.4 to 18.0 +/- 1.4 hours (p = 0.0001) and significantly reduced postexplant pulmonary vasoconstriction (p less than 0.05). Addition of isoproterenol and metabolic substrate to the AWHL model prolonged support of cardiorespiratory function and provided a reliable method for distant procurement in heart-lung transplantation.     

Donor deep hypothermia or donor pretreatment with prostaglandin E1 and single pulmonary artery flush for heart-lung graft preservation: an experimental primate study

Using cardiopulmonary bypass to cool the graft and flushing the lungs with cold crystalloid solution are the most popular methods for clinical cardiopulmonary preservation. Heart-lung transplantation was carried out in 11 cynomolgus monkeys. Donor cardiac preservation was achieved with cold crystalloid cardioplegic solution (10 ml per kilogram of body weight) in all animals. Lung preservation was achieved with a rollerhead pump and by cooling (12 degrees C) the donor in one group of 4 animals (deep hypothermia group) and infusing cold (4 degrees C) modified Euro-Collins solution (15 ml/kg X 4 minutes) into the main pulmonary artery of 7 donors pretreated with prostaglandin E1 (PGE1) (PGE1 group). PGE1 was given intravenously (0.5 to 4.0 micrograms/kg/min) beginning 15 minutes prior to aortic cross-clamping and was continued during administration of the pulmonary cooling solution. In the deep hypothermia group, no pharmacotherapy was used. Grafts were stored at 4 degrees C for about 6 hours. After heart-lung transplantation, arterial blood gases were measured on 40% inspired oxygen and 2 to 3 cm of positive end-expiratory pressure, and were significantly higher in the PGE1 group than the deep hypothermia group after 8 hours of reperfusion (p = 0.04). The partial pressure of arterial oxygen decreased significantly during the 8 hours of reperfusion in the deep hypothermia group (153 to 108 mm Hg; p = 0.01) and increased in the PGE1 group (189 to 218 mm Hg;p = 0.0002). Eighty-six percent of the animals in the PGE1 group survived more than 24 hours (p = 0.03). There were no survivors in the deep hypothermia group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distant organ procurement in clinical lung- and heart-lung transplantation. Cooling by extracorporeal circulation or hypothermic flush

The scarcity of suitable donors for single lung and heart-lung transplantation calls for methods of medium-term pulmonary preservation to allow for distant organ procurement. At our institution, the first five grafts (four heart-lung, one single lung) were cooled by means of a transportable extracorporeal circulation unit, while the last eight grafts (four heart-lung, four single lung) were flush-perfused with modified cold Euro-Collins solution. The technique of extracorporated circulation included aortic and right atrial cannulation and cooling to 12 degrees-14 degrees C (rectal temperature) using a bubble oxygenator. Bypass times ranged between 41 and 52 min. Following excision, the organs were transported in ice-cold donor blood for ischemic times from 171 to 310 min. For cold flush preservation, simultaneous coronary (cold St. Thomas's solution) and pulmonary artery perfusion (Euro-Collins solution, 50 ml/kg over 4 min) were initiated simultaneously. The organs were transported in cold Euro-Collins solution for ischemic times of 175 to 270 min. In heart-lung transplantations the first postoperative arterial PO2 upon arrival at the intensive care unit was 120 +/- 38 Torr in the extracorporeal circulation and 140 +/- 38 Torr in the Euro-Collins solution group. Six of eight patients were extubated within 48 h after cardiopulmonary grafting. We conclude that pulmonary function following heart-lung or single lung preservation with simple hypothermic flush is as good or better than that following extracorporeal circulation. Since distant organ retrieval is much more convenient without the latter, preservation using Euro-Collins solution is preferred.     

Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model.

Lazaroids are a class of novel 21 aminosteroids. They have been reported to be potent inhibitors of lipid peroxidation, which is a major contributing factor to ischemia-reperfusion injury in the lung. A Lewis rat orthotopic left lung isotransplant model was used to investigate the effects of the lazaroid U74500A on pulmonary preservation. The heart-lung blocks of donor rats were flushed with and then stored in either standard University of Wisconsin solution or University of Wisconsin solution with 30 mumol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0 degrees C, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as a thiobarbituric acid-reactive substance. Although arterial oxygen and carbon dioxide pressures and water content after 6 hours of preservation followed by reperfusion were similar in both the lazaroid and dexamethasone groups, lipid peroxide concentration was significantly higher in the dexamethasone group (0.88 +/- 0.07 mumol/gm) than in the lazaroid group (0.54 +/- 0.07 mumol/gm) (p < 0.01). After 12 hours of preservation, there were significant differences between the lazaroid and dexamethasone groups in arterial oxygen pressure (339 +/- 70 vs 27 +/- 3 mm Hg, p < 0.01), arterial carbon dioxide pressure (24.3 +/- 2.7 vs 47.7 +/- 7.0 mm Hg, p < 0.001), and lipid peroxide concentrations (0.69 +/- 0.07 vs 1.30 +/- 0.09 mumol/gm, p < 0.001). We conclude that addition of U74500A to the flush and storage solution enhances the preservation of the pulmonary graft in this transplant model.     

Colon and rectal complications after heart and lung transplantation

BACKGROUND: Gastrointestinal complications of solid organ transplantation have been well described, but little attention has been paid to colorectal disorders in particular. The purpose of this study was to identify the incidence and severity of colorectal complications among a large cohort of heart and lung transplant recipients. STUDY DESIGN: We reviewed the medical records of heart, lung, and heart-lung transplant recipients at a single institution between 1978 and 2004. Complications were identified based on need for consultation, endoscopy, or operation by a colorectal surgeon after transplantation. RESULTS: Of 1,012 patients who received transplantations (530 heart, 435 lung, 47 heart-lung), 56 patients (6%) required evaluation for 84 colorectal problems. Incidence of complications was 7% in lung transplant recipients, 6% in heart-lung transplant recipients, and 4% in heart transplant recipients. Forty-four events (52%) were considered major (diverticulitis, perforation, malignancy, and other) and 40 (48%) were minor (polyps, pseudo-obstruction treated medically or endoscopically, benign anorectal disease, and other). Twenty-three (27%) required colectomy and 9 (10%) necessitated anal operation. Thirty-six (43%) required less-invasive interventions (endoscopy, minor anorectal procedures, and other). Eighteen (21%) were treated with medical therapy alone. Six patients died from colorectal disease (7%). CONCLUSIONS: Colorectal complications are a considerable source of morbidity and mortality after heart and lung transplantation. These complications occur more frequently in patients who undergo lung and heart-lung transplantation as compared with heart transplantation alone.     

Effects of prostaglandin E1 in twelve-hour lung preservation

The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Canine heart-lung transplantation after twenty-four-hour hypothermic preservation with Belzer-UW solution

Twenty four-hour heart-lung preservation with Belzer-UW solution was studied in the canine heterotopic heart-lung transplant model. Four pairs of mongrel dogs were used. The donor heart was arrested with cardioplegic solution. The heart and the lung were flushed with UW solution, then excised en bloc and immersed in 4 degrees C UW solution for 24 hours. The graft was transplanted heterotopically into the left pneumonectomized recipient. The transplant procedure consisted of end-to-end anastomosis of two left main bronchi, end-to-side anastomosis of the descending aortas, and end-to-end anastomosis of the donor's superior vena cava to the recipient's left pulmonary artery. The recipient's right pulmonary artery was ligated after an observation period, and cardiopulmonary functions were measured during room air ventilation. In all four transplanted dogs the grafts were able to sustain the recipient's circulation. The prepreservation and posttransplant cardiac output was 71.2 +/- 21.6 ml/min/kg and 96.4 +/- 44.4 ml/min/kg; the arterial PO2 was 80.8 +/- 12.9 mm Hg and 74.1 +/- 2.7 mm Hg; and the arterial PCO2 was 25.6 +/- 5.5 mm Hg and 35.9 +/- 13.3 mm Hg, respectively. There were no significant differences between the prepreservation and posttransplant values. Posttransplant myocardial water content was within the normal range. Pulmonary vascular resistance increased significantly, to 13.8 +/- 3.7 from 8.8 +/- 5.2. Wood units, and the wet/dry ratio of the lung increased significantly, to 8.3 +/- 1.6 from 4.4 +/- 0.6. In conclusion, heart-lung grafts preserved in UW solution for 24 hours were able to sustain the recipient's circulation. Significant pulmonary edema, however, could not be prevented.     

Pulmonary function after biventricular bypass for autologous lung oxygenation.

OBJECTIVE: Biventricular bypass (BVB) with autologous lung perfusion is an attractive concept to ameliorate systemic inflammatory response by eliminating the oxygenator from the extracorporeal circulation. The effect of biventricular bypass as compared to heart-lung bypass (HLB) on pulmonary function parameters was therefore studied in an experimental model. METHODS: Heart-lung bypass using a membrane oxygenator or biventricular bypass using the autologous lung for gas exchange was performed for 120 min in an alternating series of 12 mongrel dogs with the heart arrested for 90 min by crystalloid cardioplegia and 30 min reperfusion, followed by a 120 min observation period. Systemic (CO, SVR) and pulmonary hemodynamics (PVR), extravascular lung water (EVLW, double indicator), gas exchange (FiO(2), PaO(2), PaCO(2)), lung compliance (PC), and ventilation (RMV) at FiO(2)=0.5 required to maintain PaCO(2) at 40 mmHg, were measured. Blood cell counts (Leuco, Thrombo) were performed. RESULTS: All animals were weaned from extracorporeal circulation without inotropes, no differences were observed in cardiac output and blood pressures. The following data were obtained in % change from pre-bypass values 60 min after extracorporeal circulation (*:P<0.05, HLB vs. BVB): PVR, +108 vs. +45*; EVLW, +21 vs. -2*; PC, -12 vs. +4*; PaO(2), -8 vs. +21; RMV, +21 vs. +2*; Leuco, -65 vs. -12*; Thrombo, -62 vs. -35*. CONCLUSION: During and after heart-lung bypass the lung is subject to severe ischemia-reperfusion injury as indicated by edema, cell trapping, and impaired gas exchange. The data demonstrate superior preservation of pulmonary mechanics and function after biventricular bypass as compared to heart-lung bypass and support the clinical strategy of using biventricular bypass in patients with impaired lung function.     

Asynchronous rejection of heart and lungs following cardiopulmonary transplantation

Eighteen patients have received 19 combined heart-lung allografts since March, 1982. During the maturation of our program of heart-lung transplantation, we have learned that isolated rejection of the lung can occur frequently and that exclusive dependence on the cardiac biopsy can be misleading. Of the 18 patients who received allografts, 10 are the basis for this report. The other patients were excluded because of death from excessive bleeding (1), inadequate lung preservation (2), an inability to differentiate rejection from infection (3), or an absence of rejection of either the heart or the lungs (2). Rejection of the lung was suggested, in the absence of clinical evidence of infection, by the radiographic appearance of a diffuse pulmonary infiltrate. It was confirmed by a prompt response to augmentation of maintenance immunosuppression with an intravenous pulse of methylprednisolone. The presence or absence of cardiac rejection was determined by the standard endomyocardial biopsy. Direct biopsy of the involved lung through a thoracotomy was performed in 4 patients so that a definitive histological diagnosis of rejection would reinforce the anticipated clinical diagnosis. The clinical course in 6 of the 10 patients plus the results of the open lung biopsy in 3 of them suggest that isolated rejection of the lung developed in the absence of cardiac findings. Patients responded within 12 to 24 hours to augmented immunosuppression with a dramatic improvement in the abnormal chest radiograph. In all 10 patients, either isolated lung or synchronous heart and lung rejection episodes were confined to the first six weeks after operation unless a severe alteration in the immunosuppression was made (2 patients).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term (72 hours) preservation of rat lungs

OBJECTIVE: We sought to investigate whether the addition of ethanol to a preservation solution (as an antifreeze agent) might allow a reduction of the storage temperature to 0 degrees C without causing freezing damage and improve lung function after prolonged (72 hours) ischemia. METHODS: Lungs from Sprague-Dawley rats were ventilated and perfused ex vivo at 37 degrees C for 60 minutes in the following experimental groups: (1) the no ischemia and reperfusion (no I-R) group (n = 7), in which lungs were studied immediately after harvesting; (2) the LPD24 (n = 7) and (3) LPD72 (n = 8) groups, in which, after harvesting, lungs were flushed and immersed in low-potassium dextran solution and stored deflated at 10 degrees C for 24 and 72 hours, respectively, until reperfusion; and (4) the TEST72 group (n = 9), in which lungs were flushed and immersed in Krebs-Henseleit buffer with added ethanol (10 mL/L) after harvesting and stored deflated at 0 degrees C for 72 hours until reperfusion. RESULTS: Compared with the no I-R group, the other 3 groups had worse lung function, higher lung water content, and evidence of cell injury at reperfusion (P <.01). However, lung function at reperfusion (assessed on the basis of either effluent Po(2), peak airway pressure, or mean arterial pulmonary pressure) was better (P <.01) in the TEST72 group than in the LPD24 or LPD72 groups. Paradoxically, lung cell structure was better preserved in the LPD24 group than in the TEST72 group (or the LPD72 group). CONCLUSIONS: In this experimental model of rat lung ischemia-reperfusion injury, a low preservation temperature (0 degrees C) combined with the addition of ethanol to the preservation solution improves lung function at reperfusion after 72 hours of ischemia but fails to maintain lung cell structure.     

In-situ topical cooling of lung grafts: early graft function and surfactant analysis in a porcine single lung transplant model.

OBJECTIVE: Improvement of organ preservation is essential to facilitate acceptance of marginal donor lungs for transplantation. Thus, recruiting non-heart-beating donors (NHBD) may be one reasonable strategy to augment the organ-pool especially in the field of pulmonary transplantation. Topical cooling (TC) of donor lungs could provide fast organ-protection and is an available procedure even in smaller centers. In this study transplanted lung function and surfactant activity in same lungs, which were preserved by TC, were assessed following transplantation. METHODS: Twelve porcine allogeneic single lung transplants were performed. Six lungs that were flush preserved through the antegrade route served as controls. The other six lungs were preserved by TC for 30 min after induction of cardiac arrest by repeated application of cold saline (8 degrees C) to both pleural cavities. Lungs of both groups were stored in LPD solution for 24 h at 8 degrees C. After transplantation, the recipient's right bronchus and right pulmonary artery were clamped. Major endpoints included early graft function over a period of 7 h. Hemodynamic measures and respiratory functions were recorded in 30-min intervals. Surfactant function was determined before transplantation and 2 h after reperfusion by broncho-alveolar lavage fluid analysis. RESULTS: Only four animals of the control-group survived the 7 h reperfusion period. Right heart failure occurred in two animals after 150 and 240 min of reperfusion. All six animals in the TC group survived the observation period. Pulmonary vascular resistance (p<0.01), pulmonary artery pressure (p=0.03), and lung tissue water content remained significantly lower in topically cooled allografts (p=0.01) vs. controls. Surfactant function after transplantation was comparable in both groups with a trend towards lower protein contents (p=0.07) in the broncho-alveolar fluid of grafts after TC. CONCLUSIONS: In-situ TC seems to be a reliable strategy to preserve lungs for up to 24 h. It even surpasses the results of LPD-perfused grafts in hemodynamic function and survival time.