- Email: [email protected]
Beneficial effects of tumor necrosis factor converting enzyme inhibitor on reimplantation lung injury
S150
Abstracts
L.W. Miller,1 S.J. Park,2 J.W. Long,3 D.E. Renlund,3 A.J. Boyle,1 M.M. Colvin-Adams,1 1Cardiology, University of Minnesota, Minneapolis, MN; 2Surgery, University of Minnesota, Minneapolis, MN; 3Surgery, LDS Hospital, Salt Lake City, UT Purpose: Serious infection was the leading cause of death in the REMATCH trial which compared the benefit and complications of VAD support versus medical therapy for patients with end stage heart failure who were not eligible for transplantation. During the trial it became apparent that advancements in infection prevention were needed. Two centers had previously adopted novel, extensive approaches to infection prevention. We report the incidence of infection at our two centers and the impact of disseminating a rigorous protocol to others. Methods: 19 patients from the two centers were enrolled in the REMATCH trial and received a HeartMate VE LVAD (Thoratec Corp, California). All patients were managed with rigorous perioperative preventative measures, including broad spectrum, antibiotic prophylaxis, uniquely were managed with abdominal binders for percutanous lead immobilization, and aggressively supported by the medical team. The cumulative days of VAD support in the 19 patients was 11,243 days, with a mean of 592, and a range of 3-1131 days. The patients were similar to the entire cohort from the REMATCH trial. Results: In these two centers the incidence of infection in the 19 patients was: (a) sepsis as cause of death ⫽ 0, (b) all sepsis events ⫽ 3, (c) localized patient infection ⫽ 21, (d) LVAD perc lead exit site infection ⫽ 8, (e) LVAD pocket infection ⫽ 0, (f) LVAD housing/ inflow/outflow tract infection ⫽ 0 and (g) repeat hospitalization for treatment of infection ⫽ 0. After developing an infection prevention protocol incorporating rigorous practices at these two centers, it was disseminated to all REMATCH investigators. This was associated with reduction in incidence of serious infection for the entire REMATCH LVAD cohort (68 patients) from 68% to 41%. Conclusions: This experience demonstrates the importance of rigorous infection prevention protocols, and demonstrates that infection with long-term LVAD support can be minimized.
319 FIRST GERMAN EXPERIENCE WITH THE CARDIOWEST TAHREPORT FROM A SINGLE CENTER A. El-Banayosy,1 L. Arusoglu,1 M. Morshuis,1 L. Kizner,1 P. Sarnowski,1 R. Koerfer,1 1Department of Cardiothoracic Surgery, Heart and Diabetescenter NRW, Bad Oeynhausen, Germany Purpose: Many reports have demonstrated the efficacy of ventricular assist devices (VAD’S) as bridge to cardiac transplantation (BTT). However, there are some limitations-technical and medical-in their use. In some terminally ill patients (pts) the CardioWest TAH is more beneficial than a VAD. For these cases, the application of a TAH might open a new therapy window. We report our experience with 22 pts supported with the CardioWest TAH in our center. Procedures: From October 2001 until June 2003 22 pts (age 17-77 years, mean 46; 4 female, 18 male, mean BSA 1.9) with cardiogenic shock (CS) were supported with the TAH. Etiology of CS was DCM in 6 pts, ICM in 4 pts, postcardiotomy heart-failure in 4 pts, fulminate myocarditis in 3 pts, acute myocardial infarction in 4 pts and primary graft failure in 1 pt. Risk factors emphasizing the severity of the illness were: 54% of pts had previous cardiac surgery, 69% needed IABP support, 59% other mechanical circulatory support, 94% were ventilated, 62% needed CVVH and 56% had recent CPR. Mean total bilirubin was 3.1 mg/dl and mean creatinine 2.1 mg/dl. Results: Almost all pts recovered from multiple organ failure and gained a mobile state, which was limited though to in-hospital treatment due to the large driving console of the CardioWest TAH.
The Journal of Heart and Lung Transplantation February 2004
Duration of support varied from 5-330 days (mean 96). 9 pts (41%) were transplanted, 3 are waiting for HTX (14%) and 10 pts died on the system (45%). Main complicationes were bleeding (18%), liver failure (18%), abdominal complications (14%). Conclusion: The results show the efficacy and safety of the CardioWest TAH as bridging device for the sickest pts. A portable driver would improve quality of life for these pts and allow out-of-hospital treatment, thus widening the indication for a TAH.
320 LUNG TRANSPLANTATION USING LUNGS FROM DONORS 50 YEARS OF AGE AND OLDER S. Fischer,1 P. Struckmeier,1 R. Tessmann,1 A.R. Simon,1 J. Niedermeyer,1 B. Gohrbandt,1 G. Warnecke,1 A. Haverich,1 M. Strueber,1 1Hannover Thoracic Transplant Program, Hannover Medical School, Hannover, NS, Germany A shortage of donors has led to the progressive expansion of criteria for donor selection in lung transplantation. The outcome of lung transplant (LTx) recipients from donors aged 50 years an older is analysed systematically. From 12/2000 to 06/2003, 31 recipients received lungs from donors 50 years of age and older (range 50-64, mean 54 ⫾ 3 years). This group of recipients was compared to 131 patients receiving lungs from donors younger than 50 years of age (range 7-49, mean 32 ⫾ 11 years) during the same time period. Age, recipient gender and indication for transplant did not differ significantly among groups. Also, the numbers of different types of transplants (bilateral or single LTx) performed was equal with 90% bilateral and 10% single LTx procedures in both cohorts. The proportion of smokers (30% vs 29%, p ⫽ 0.1), PaO2 before lung retrieval (420 ⫾ 131 vs 411 ⫾ 100 mmHg, p ⫽ 0,4), and the length of ischemic time (left lung 359 ⫾ 87/right lung 299 ⫾ 93 min vs left lung 339 ⫾ 67/right lung 258 ⫾ 59 min, p ⫽ 0,4 and p ⫽ 0,07, respectively) did not differe significantly between the older and younger donor group. The following posttransplant parameters were also not statistically different among groups: first paO2 at ICU arrival (older donor group: 232 ⫾ 122 vs 270 ⫾ 114 mmHg in the young donor group, respectively; p ⫽ 0,1), mechanical ventilation time (272 ⫾ 374 vs 259 ⫾ 329 hrs, respectively; p ⫽ 0,5) and length of stay in the ICU (14 ⫾ 16 vs 13 ⫾ 14 days, respectively; p ⫽ 0,7). Recipient survival in the older and younger donor group at 30-days, 3, 6 and 12 months was 83,9 ⫾ 7%, 83,9 ⫾ 7%, 79,6 ⫾ 8% and 79,6 ⫾ 8% vs 84,9 ⫾ 3%, 81,4 ⫾ 4%, 79.6 ⫾ 4% and 76,2 ⫾ 4%, respectively; p ⫽ 0,9. Lung grafts from elderly donors have been considered as marginal organs for transplantation. However, this study indicates that transplantation of lungs from carefully selected donors 50 years of age and older may lead to similar short and mid-term outcome compared to lungs from younger donors. The utilization of lungs from elderly donors could help to increase the number of donor organs in lung transplantation. 321 BENEFICIAL EFFECTS OF TUMOR NECROSIS FACTOR CONVERTING ENZYME INHIBITOR ON REIMPLANTATION LUNG INJURY T. Goto,1 A. Ishizaka,2 M. Kohno,1 M. Sawafuji,1 K. Kobayashi,1 1 Department of Surgery, Keio University, Tokyo, Japan; 2 Department of Medicine, Keio University, Tokyo, Japan Despite the well-known pro-inflammatory effects of tumor necrosis factor (TNF), role of TNF in the pathogenesis of lung injury following lung transplantation remains unclear. TNF has two forms with apparently different biological activities, a membrane associated form and a soluble form generated from the membrane-bound protein by proteolytic cleavage with TNF converting enzyme (TACE). TACE
The Journal of Heart and Lung Transplantation Volume 23, Number 2S
inhibition might prevent TNF-induced tissue injury while preserving benefits of TNF, such as host defense. Inbred male Lewis rats were used as both donor and recipient animals, and they were subjected to left lung isotransplantation. In this model, donor lungs were flushed with Euro-Collins solution with or without 1 mg/ml TACE-inhibitor (n ⫽ 10 for each group). After 6 hours of ischemia, the left lung was transplanted into recipient rat and reperfused for 4 hours. The animals were injected intravenously with 125I-labeled albumin 3 hours after the onset of reperfusion as a marker of pulmonary albumin leakage. Transvascular flux of 125I-albumin was assessed by using the concentration ratio of lung tissue to plasma (T/P ratio) and that of BALF supernatant to plasma (B/P ratio) per unit weight, which were used as parameters of pulmonary endothelial and alveolar septal damage, respectively. The group receiving Euro-Collins solution with TACE-inhibitor showed significantly lower T/P and B/P ratio than control group. Furthermore, the administration of TACE-inhibitor attenuated sequestration of both neutrophils and macrophages in the alveolar space and following tissue injury observed histologically, proving a causal role of locally produced soluble TNF in this transplant model. In addition, decreased levels of chemokines (MCP-1 and CINC-1), lower neutrophil elastase activity, lower high mobility group box-1 (HMGB-1) protein and lower soluble E-cadherin level were observed in bronchoalveolar lavage fluid collected from the group treated with the TACE-inhibitor. We concluded that TACE inhibition could attenuate post-transplantation lung injury where TNF plays the central role. 322 LONG-TERM PRESERVATION USING A NEW APPARATUS COMBINED WITH SUPPRESSION OF PROINFLAMMATORY CYTOKINES IMPROVES DONOR HEART FUNCTION FOLLOWING TRANSPLANTATION IN A CANINE MODEL K. Oshima,1 I. Takeyoshi,1 J. Mohara,1 H. Tsutsumi,1 S. Ishikawa,1 K. Matsumoto,2 Y. Morishita,1 1Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Gunma, Japan; 2Department of Pathology, Nippon Medical School Second Hospital, Kawasaki, Kanagawa, Japan Objective: In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion combined with suppression of proinflammatory cytokines improves donor heart function following Tx in a canine model. Materials and Methods: Coronary vascular beds of adult mongrel dogs were washed out with UW solution following cardiac arrest obtained with a glucose-insulin-potassium solution. The heart was excised and preserved for 12 hours with a combination of immersion and coronary perfusion using our apparatus. In the coronary perfusion (CP) group (n ⫽ 7), a 4°C UW solution was used for both immersion and coronary perfusion. In the FR167653 (FR-CP) group (n ⫽ 6), a 4°C UW solution supplemented with 20 mg/L of the anti-inflammatory agent, FR167653, was used. After 12-hour preservation, orthotopic Tx was performed under cardiopulmonary bypass (CPB). Recipient animals were weaned from CPB 1 hour after reperfusion and were observed for 2 hours. At 1 and 2 hour after weaning from CPB, hemodynamics were compared with preoperative values of donor animals with 10 mmHg right atrial pressure and a 5-g/kg/min dopamine. Serum levels of TNF-␣ from the coronary sinus and electron microscopic studies were compared between the two groups. Results: Two hour after weaning from CPB, cardiac output, left ventricular pressure and -LVdp/dt were significantly higher (p ⬍ 0.05) in the FR-CP group than in the CP group. Electron microscopic studies showed that glycogen was well preserved in the FR-CP group comparing with the CP group. Serum levels of TNF-␣ were significantly (p ⬍ 0.05) reduced in the FR-CP group than in the CP group 2
Abstracts
S151
hour after weaning from CPB (161 ⫾ 54 pg/dl vs 642 ⫾ 636 pg/dl, respectively). Conclusion: The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of proinflammatory cytokines improves donor heart function following transplantation. 323 DOES DONOR CATECHOLAMINE ADMINISTRATION AFFECT EARLY LUNG FUNCTION POST-TRANSPLANTATION? M.E. Mukadam,1 D.K. Harrington,1 I.C. Wilson,1 S.J. Rooney,1 D.P. Pagano,1 R.D. Thompson,1 R.S. Bonser,1 1Cardiothoracic Transplantation Unit, University Hospital,, Birmingham, West Midlands, United Kingdom Statement of Purpose: Exogenous donor catecholamine administration (EDCA) appears to improve outcome in liver and kidney transplantation but worsens prognosis in heart transplantation. EDCA can also increase alveolar fluid clearance following brainstem death. Our aim was to assess the effect of EDCA on early lung function following lung transplantation (LTx). Statement of Procedures: A retrospective analysis of donor and 6 hour recepient gas exchange was performed in a series of 60 consecutive LTx (27 single: 33 bilateral). The reduction in PaO2/FiO2 ratio (⌬PaO2/FiO2) from pre-retrieval to 6 hours post-implantation was compared according to donor catecholamine (but not vasopressin) treatment at the time of organ procurement. Summary of Results: Catecholamines were used in 29/60 donors. There was no significant difference in initial mean PaO2/FiO2 ratio between catecholamine treated (504-SD 74) and untreated (486-SD 86) donors . Although a significant fall in PaO2/FiO2 ratio was seen in both groups: catecholamine un-treated (⌬PaO2/FiO2 200-SD 137,p ⬍ 0.001)and treated (⌬PaO2/FiO2 272-SD111, p ⬍ 0.001), this fall was significantly greater in the catecholamine treated group (p ⫽ 0.05). ⌬PaO2/FiO2 did not correlate with ischaemic time, preservation technique, operation type or reperfusion strategy. Conclusion: Impairment in early gas exchange is a uniform observation post-lung procurement, preservation and implantation. This impairment is increased when donors receive exogenous catecholamines. Possible explanations include a direct effect on donor left atrial pressure or other haemodynamic parameters. Alternatively a requirement for EDCA may identify a sub-group of donors in whom peri-brainstem phenomena, previously shown to affect graft function, are more severe. 324 EFFECT ON CARDIOPLEGIC SOLUTION WITH POLY(ADPRIBOSE) SYNTHETASE (PARS) INHIBITORS, ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN RAT HEARTS K. Yamazaki,1 S. Miwa,1 K. Ueda,1 S. Tanaka,1 S. Toyokuni,1 O. Unimonh,1 K. Takaba,1 T. Ikeda,1 K. Nishimura,1 M. Komeda,1 1 Department of Cardiovascular Surgery, Kyoto University, Kyoto, Kyoto, Japan Objective: Ischemia-reperfusion injury is thought to be a main cause of organ failure after transplantation. Poly(adenosine 5⬘-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury in myocardial infarction associated with oxidative stress. We investigated the efficacy of cardioplegic solutions containing a PARS inhibitor against ischemia-reperfusion injury. Methods: Isolated hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution given at 30-min intervals and then reperfused for 20 min. The Control group (n ⫽ 8) received standard cardioplegic solution and
Abstracts
L.W. Miller,1 S.J. Park,2 J.W. Long,3 D.E. Renlund,3 A.J. Boyle,1 M.M. Colvin-Adams,1 1Cardiology, University of Minnesota, Minneapolis, MN; 2Surgery, University of Minnesota, Minneapolis, MN; 3Surgery, LDS Hospital, Salt Lake City, UT Purpose: Serious infection was the leading cause of death in the REMATCH trial which compared the benefit and complications of VAD support versus medical therapy for patients with end stage heart failure who were not eligible for transplantation. During the trial it became apparent that advancements in infection prevention were needed. Two centers had previously adopted novel, extensive approaches to infection prevention. We report the incidence of infection at our two centers and the impact of disseminating a rigorous protocol to others. Methods: 19 patients from the two centers were enrolled in the REMATCH trial and received a HeartMate VE LVAD (Thoratec Corp, California). All patients were managed with rigorous perioperative preventative measures, including broad spectrum, antibiotic prophylaxis, uniquely were managed with abdominal binders for percutanous lead immobilization, and aggressively supported by the medical team. The cumulative days of VAD support in the 19 patients was 11,243 days, with a mean of 592, and a range of 3-1131 days. The patients were similar to the entire cohort from the REMATCH trial. Results: In these two centers the incidence of infection in the 19 patients was: (a) sepsis as cause of death ⫽ 0, (b) all sepsis events ⫽ 3, (c) localized patient infection ⫽ 21, (d) LVAD perc lead exit site infection ⫽ 8, (e) LVAD pocket infection ⫽ 0, (f) LVAD housing/ inflow/outflow tract infection ⫽ 0 and (g) repeat hospitalization for treatment of infection ⫽ 0. After developing an infection prevention protocol incorporating rigorous practices at these two centers, it was disseminated to all REMATCH investigators. This was associated with reduction in incidence of serious infection for the entire REMATCH LVAD cohort (68 patients) from 68% to 41%. Conclusions: This experience demonstrates the importance of rigorous infection prevention protocols, and demonstrates that infection with long-term LVAD support can be minimized.
319 FIRST GERMAN EXPERIENCE WITH THE CARDIOWEST TAHREPORT FROM A SINGLE CENTER A. El-Banayosy,1 L. Arusoglu,1 M. Morshuis,1 L. Kizner,1 P. Sarnowski,1 R. Koerfer,1 1Department of Cardiothoracic Surgery, Heart and Diabetescenter NRW, Bad Oeynhausen, Germany Purpose: Many reports have demonstrated the efficacy of ventricular assist devices (VAD’S) as bridge to cardiac transplantation (BTT). However, there are some limitations-technical and medical-in their use. In some terminally ill patients (pts) the CardioWest TAH is more beneficial than a VAD. For these cases, the application of a TAH might open a new therapy window. We report our experience with 22 pts supported with the CardioWest TAH in our center. Procedures: From October 2001 until June 2003 22 pts (age 17-77 years, mean 46; 4 female, 18 male, mean BSA 1.9) with cardiogenic shock (CS) were supported with the TAH. Etiology of CS was DCM in 6 pts, ICM in 4 pts, postcardiotomy heart-failure in 4 pts, fulminate myocarditis in 3 pts, acute myocardial infarction in 4 pts and primary graft failure in 1 pt. Risk factors emphasizing the severity of the illness were: 54% of pts had previous cardiac surgery, 69% needed IABP support, 59% other mechanical circulatory support, 94% were ventilated, 62% needed CVVH and 56% had recent CPR. Mean total bilirubin was 3.1 mg/dl and mean creatinine 2.1 mg/dl. Results: Almost all pts recovered from multiple organ failure and gained a mobile state, which was limited though to in-hospital treatment due to the large driving console of the CardioWest TAH.
The Journal of Heart and Lung Transplantation February 2004
Duration of support varied from 5-330 days (mean 96). 9 pts (41%) were transplanted, 3 are waiting for HTX (14%) and 10 pts died on the system (45%). Main complicationes were bleeding (18%), liver failure (18%), abdominal complications (14%). Conclusion: The results show the efficacy and safety of the CardioWest TAH as bridging device for the sickest pts. A portable driver would improve quality of life for these pts and allow out-of-hospital treatment, thus widening the indication for a TAH.
320 LUNG TRANSPLANTATION USING LUNGS FROM DONORS 50 YEARS OF AGE AND OLDER S. Fischer,1 P. Struckmeier,1 R. Tessmann,1 A.R. Simon,1 J. Niedermeyer,1 B. Gohrbandt,1 G. Warnecke,1 A. Haverich,1 M. Strueber,1 1Hannover Thoracic Transplant Program, Hannover Medical School, Hannover, NS, Germany A shortage of donors has led to the progressive expansion of criteria for donor selection in lung transplantation. The outcome of lung transplant (LTx) recipients from donors aged 50 years an older is analysed systematically. From 12/2000 to 06/2003, 31 recipients received lungs from donors 50 years of age and older (range 50-64, mean 54 ⫾ 3 years). This group of recipients was compared to 131 patients receiving lungs from donors younger than 50 years of age (range 7-49, mean 32 ⫾ 11 years) during the same time period. Age, recipient gender and indication for transplant did not differ significantly among groups. Also, the numbers of different types of transplants (bilateral or single LTx) performed was equal with 90% bilateral and 10% single LTx procedures in both cohorts. The proportion of smokers (30% vs 29%, p ⫽ 0.1), PaO2 before lung retrieval (420 ⫾ 131 vs 411 ⫾ 100 mmHg, p ⫽ 0,4), and the length of ischemic time (left lung 359 ⫾ 87/right lung 299 ⫾ 93 min vs left lung 339 ⫾ 67/right lung 258 ⫾ 59 min, p ⫽ 0,4 and p ⫽ 0,07, respectively) did not differe significantly between the older and younger donor group. The following posttransplant parameters were also not statistically different among groups: first paO2 at ICU arrival (older donor group: 232 ⫾ 122 vs 270 ⫾ 114 mmHg in the young donor group, respectively; p ⫽ 0,1), mechanical ventilation time (272 ⫾ 374 vs 259 ⫾ 329 hrs, respectively; p ⫽ 0,5) and length of stay in the ICU (14 ⫾ 16 vs 13 ⫾ 14 days, respectively; p ⫽ 0,7). Recipient survival in the older and younger donor group at 30-days, 3, 6 and 12 months was 83,9 ⫾ 7%, 83,9 ⫾ 7%, 79,6 ⫾ 8% and 79,6 ⫾ 8% vs 84,9 ⫾ 3%, 81,4 ⫾ 4%, 79.6 ⫾ 4% and 76,2 ⫾ 4%, respectively; p ⫽ 0,9. Lung grafts from elderly donors have been considered as marginal organs for transplantation. However, this study indicates that transplantation of lungs from carefully selected donors 50 years of age and older may lead to similar short and mid-term outcome compared to lungs from younger donors. The utilization of lungs from elderly donors could help to increase the number of donor organs in lung transplantation. 321 BENEFICIAL EFFECTS OF TUMOR NECROSIS FACTOR CONVERTING ENZYME INHIBITOR ON REIMPLANTATION LUNG INJURY T. Goto,1 A. Ishizaka,2 M. Kohno,1 M. Sawafuji,1 K. Kobayashi,1 1 Department of Surgery, Keio University, Tokyo, Japan; 2 Department of Medicine, Keio University, Tokyo, Japan Despite the well-known pro-inflammatory effects of tumor necrosis factor (TNF), role of TNF in the pathogenesis of lung injury following lung transplantation remains unclear. TNF has two forms with apparently different biological activities, a membrane associated form and a soluble form generated from the membrane-bound protein by proteolytic cleavage with TNF converting enzyme (TACE). TACE
The Journal of Heart and Lung Transplantation Volume 23, Number 2S
inhibition might prevent TNF-induced tissue injury while preserving benefits of TNF, such as host defense. Inbred male Lewis rats were used as both donor and recipient animals, and they were subjected to left lung isotransplantation. In this model, donor lungs were flushed with Euro-Collins solution with or without 1 mg/ml TACE-inhibitor (n ⫽ 10 for each group). After 6 hours of ischemia, the left lung was transplanted into recipient rat and reperfused for 4 hours. The animals were injected intravenously with 125I-labeled albumin 3 hours after the onset of reperfusion as a marker of pulmonary albumin leakage. Transvascular flux of 125I-albumin was assessed by using the concentration ratio of lung tissue to plasma (T/P ratio) and that of BALF supernatant to plasma (B/P ratio) per unit weight, which were used as parameters of pulmonary endothelial and alveolar septal damage, respectively. The group receiving Euro-Collins solution with TACE-inhibitor showed significantly lower T/P and B/P ratio than control group. Furthermore, the administration of TACE-inhibitor attenuated sequestration of both neutrophils and macrophages in the alveolar space and following tissue injury observed histologically, proving a causal role of locally produced soluble TNF in this transplant model. In addition, decreased levels of chemokines (MCP-1 and CINC-1), lower neutrophil elastase activity, lower high mobility group box-1 (HMGB-1) protein and lower soluble E-cadherin level were observed in bronchoalveolar lavage fluid collected from the group treated with the TACE-inhibitor. We concluded that TACE inhibition could attenuate post-transplantation lung injury where TNF plays the central role. 322 LONG-TERM PRESERVATION USING A NEW APPARATUS COMBINED WITH SUPPRESSION OF PROINFLAMMATORY CYTOKINES IMPROVES DONOR HEART FUNCTION FOLLOWING TRANSPLANTATION IN A CANINE MODEL K. Oshima,1 I. Takeyoshi,1 J. Mohara,1 H. Tsutsumi,1 S. Ishikawa,1 K. Matsumoto,2 Y. Morishita,1 1Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Gunma, Japan; 2Department of Pathology, Nippon Medical School Second Hospital, Kawasaki, Kanagawa, Japan Objective: In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion combined with suppression of proinflammatory cytokines improves donor heart function following Tx in a canine model. Materials and Methods: Coronary vascular beds of adult mongrel dogs were washed out with UW solution following cardiac arrest obtained with a glucose-insulin-potassium solution. The heart was excised and preserved for 12 hours with a combination of immersion and coronary perfusion using our apparatus. In the coronary perfusion (CP) group (n ⫽ 7), a 4°C UW solution was used for both immersion and coronary perfusion. In the FR167653 (FR-CP) group (n ⫽ 6), a 4°C UW solution supplemented with 20 mg/L of the anti-inflammatory agent, FR167653, was used. After 12-hour preservation, orthotopic Tx was performed under cardiopulmonary bypass (CPB). Recipient animals were weaned from CPB 1 hour after reperfusion and were observed for 2 hours. At 1 and 2 hour after weaning from CPB, hemodynamics were compared with preoperative values of donor animals with 10 mmHg right atrial pressure and a 5-g/kg/min dopamine. Serum levels of TNF-␣ from the coronary sinus and electron microscopic studies were compared between the two groups. Results: Two hour after weaning from CPB, cardiac output, left ventricular pressure and -LVdp/dt were significantly higher (p ⬍ 0.05) in the FR-CP group than in the CP group. Electron microscopic studies showed that glycogen was well preserved in the FR-CP group comparing with the CP group. Serum levels of TNF-␣ were significantly (p ⬍ 0.05) reduced in the FR-CP group than in the CP group 2
Abstracts
S151
hour after weaning from CPB (161 ⫾ 54 pg/dl vs 642 ⫾ 636 pg/dl, respectively). Conclusion: The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of proinflammatory cytokines improves donor heart function following transplantation. 323 DOES DONOR CATECHOLAMINE ADMINISTRATION AFFECT EARLY LUNG FUNCTION POST-TRANSPLANTATION? M.E. Mukadam,1 D.K. Harrington,1 I.C. Wilson,1 S.J. Rooney,1 D.P. Pagano,1 R.D. Thompson,1 R.S. Bonser,1 1Cardiothoracic Transplantation Unit, University Hospital,, Birmingham, West Midlands, United Kingdom Statement of Purpose: Exogenous donor catecholamine administration (EDCA) appears to improve outcome in liver and kidney transplantation but worsens prognosis in heart transplantation. EDCA can also increase alveolar fluid clearance following brainstem death. Our aim was to assess the effect of EDCA on early lung function following lung transplantation (LTx). Statement of Procedures: A retrospective analysis of donor and 6 hour recepient gas exchange was performed in a series of 60 consecutive LTx (27 single: 33 bilateral). The reduction in PaO2/FiO2 ratio (⌬PaO2/FiO2) from pre-retrieval to 6 hours post-implantation was compared according to donor catecholamine (but not vasopressin) treatment at the time of organ procurement. Summary of Results: Catecholamines were used in 29/60 donors. There was no significant difference in initial mean PaO2/FiO2 ratio between catecholamine treated (504-SD 74) and untreated (486-SD 86) donors . Although a significant fall in PaO2/FiO2 ratio was seen in both groups: catecholamine un-treated (⌬PaO2/FiO2 200-SD 137,p ⬍ 0.001)and treated (⌬PaO2/FiO2 272-SD111, p ⬍ 0.001), this fall was significantly greater in the catecholamine treated group (p ⫽ 0.05). ⌬PaO2/FiO2 did not correlate with ischaemic time, preservation technique, operation type or reperfusion strategy. Conclusion: Impairment in early gas exchange is a uniform observation post-lung procurement, preservation and implantation. This impairment is increased when donors receive exogenous catecholamines. Possible explanations include a direct effect on donor left atrial pressure or other haemodynamic parameters. Alternatively a requirement for EDCA may identify a sub-group of donors in whom peri-brainstem phenomena, previously shown to affect graft function, are more severe. 324 EFFECT ON CARDIOPLEGIC SOLUTION WITH POLY(ADPRIBOSE) SYNTHETASE (PARS) INHIBITORS, ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN RAT HEARTS K. Yamazaki,1 S. Miwa,1 K. Ueda,1 S. Tanaka,1 S. Toyokuni,1 O. Unimonh,1 K. Takaba,1 T. Ikeda,1 K. Nishimura,1 M. Komeda,1 1 Department of Cardiovascular Surgery, Kyoto University, Kyoto, Kyoto, Japan Objective: Ischemia-reperfusion injury is thought to be a main cause of organ failure after transplantation. Poly(adenosine 5⬘-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury in myocardial infarction associated with oxidative stress. We investigated the efficacy of cardioplegic solutions containing a PARS inhibitor against ischemia-reperfusion injury. Methods: Isolated hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution given at 30-min intervals and then reperfused for 20 min. The Control group (n ⫽ 8) received standard cardioplegic solution and