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283: Lactate Production during Acellular Normothermic Ex Vivo Pig and Human Lung Perfusion
S96
The Journal of Heart and Lung Transplantation, Vol 29, No 2S, February 2010
Methods and Materials: Lung Preparation: Lungs were harvested from 6 adult sheep and perfused with albumin based solution via the pulmonary artery. Lungs were warmed to 37°C; ventilation initiated at 30°C; PA pressure limited to 20 mmHg; mean airway pressure limited to 25 cm H2O. Perfusion goal was 60-100 cc/kg/min for 2 hours. Quantitated Ventilation and Perfusion: A 64 MDCT scanner obtained spiral volumetric scans at total lung capacity every 40 minutes, quantifying tissue and air volumes. Perfusion flow rates were ranged from 50, 75, 100 and 125 cc/kg/min at the end of the 2 hours. Regional pulmonary blood flow (PBF) was quantified using contrast MDCT scans at each flow rate. Results: Perfusion goals were met. Tissue edema increased 9-20% in 5 lungs and decreased 3% in one lung. PVR ranged from 1-9 Wood u, Compliance ranged from 5-57 cc/ cm H2O. Non-dependent perfusion increased with flow rates. Figure 1 shows tissue edema and aeration over 2 hours.[figure1]Figure 2 shows regional perfusion with increased flow rates.[figure2]
Methods and Materials: Lungs from Yorkshire pigs were randomized into two groups: a) 0h cold ischemic time (CIT) (n⫽3) or b) 12h CIT (n⫽6) prior to EVLP. Perfusate (Steen solution, Vitrolife) L, pyruvate (P) and glucose (G) levels were measured over 12 hours. In order to assess the proportional increase in production, the L/P ratio was calculated. We subsequently measured L/P ratio in the perfusate of human lungs (n⫽12) during clinical use of EVLP and lungs rejected for clinical transplant (n⫽2) during experimental use of EVLP. Results: L/P ratio following 12h EVLP was significantly higher and the G level was lower in the 12h CIT group as compared to the 0h CIT group in pigs (Fig 1A). Rejected human lung cases had an L/P ratio at 4h EVLP that was significantly higher than the successfully transplanted EVLP human lungs (Fig. 1B).[figure1] Conclusions: L production or washout from the lung continues to occur over time in the EVLP circuit. While lungs that perform well and are successfully transplanted have some elevation in the L level, the rejected human lungs studied had significantly higher L/P ratios during EVLP. Further work is required to determine the implication of the L/P ratio and to determine its value as an EVLP marker of severity of lung injury. 284 Ex-Vivo Repair of Donor Lungs- Is Cell-Free Solution Superior to Blood Perfusion? S. Wipper,1 Y. Rittberg,1 A. Dupree,1 E. Youbert-Hubner,1 B. Reiter,1 A. Koops,2 H. Reichenspurner,1 F.M. Wagner.1 1University Heart Center Hamburg, Hamburg, Germany; 2University Hospital HamburgEppendorf, Hamburg, Germany.
Conclusions: Regional perfusion and ventilation can be quantified with MDCT imaging creating a “donor lung functional assessment tool.” 283 Lactate Production during Acellular Normothermic Ex Vivo Pig and Human Lung Perfusion T. Koike, J.C. Yeung, M. Cypel, M. Rubacha, Y. Matsuda, M. Liu, T.K. Waddell, S. Keshavjee. University of Toronto, Toronto, ON, Canada. Purpose: Serum lactate (L) is generally related to poor prognosis in disease states and used as a marker of hypoxia and poor tissue perfusion. The measured L level in serum reflects the balance between L production and metabolism. In the ex vivo lung perfusion (EVLP) circuit however, without some organs present for removal, L levels will build up over time and the significance of the specific L level is unknown. We sought to characterize L levels in damaged and healthy lungs during acellular normothermic EVLP.
Purpose: To evaluate whether ex-vivo reconditioning of donor lungs in a closed perfusion circuit using cell-free Steen-solution is superior to erythrocyte-containing solution. Methods and Materials: Perfadex preserved pig lungs were perfused in a closed-circuit (centrifugal blood-pump, heparin-coated tubing/deoxigenator, leucocyte filter) for 6hrs according to standardized protocol. Perfusion started at 21°C to reach 37°C within 30 minutes, pressure-controlled ventilation started at 32°C (FiO2⫽0,5). We compared 2 groups (n⫽6 each): Gr.1 priming with washed-erythrocytes plus Steen-solution (Hb5,0mg/dl); Gr.2 priming only Steen-Solution. Respiratory/hemodynamic parameters were documented pre-harvest and hourly during reperfusion as well as pre-/post-reperfusion wet-dry ratios. Deflation (PDI) was indexed after ventilator disconnection (1 ⫽ normal to 5 ⫽ no collaps ⫹ foamy edema), histology evaluated by semiquantitative score. Results: All lungs were successfully reperfused for 6hrs. At study endpoint 2/6 lungs in Gr.1 and 1/6 in Gr.2 showed macroscopic edema (⫽not transplantable). PDI was significantly better in Gr.2 (1.4⫾0.2 vs. 2.4⫾0.6; p⬍0.05) with correspondingly lower wet/dry ratios (4.2⫾0.2 vs. 4.8⫾0.3; p⬍0.05). Pulmonary vascular resistance was significantly lower during cell-free perfusion (Gr.2) after second hour (456⫾130 vs. 736⫾148dynes) until study end-point (570⫾194 vs.1120⫾380dynes; p⬍0.05). Pulmonary compliance and oxygenation capacity were stable and comparable between groups throughout the study (Gr.1 vs Gr.2: 43⫾7 vs. 45⫾6ml/cmH2O & 349⫾68 vs. 364⫾64mmHg; p⫽n.s.). Histology confirmed those results. Conclusions: Cell-free ex-vivo perfusion using a closed circuit reduces elevated PVR and pulmonary edema but fails to achieve 100% transplantability of lungs perfused for 6hrs. 285 Waitlist Mortality among Young Patients with Idiopathic or Famililal Pulmonary Hypertension Awaiting Lung Transplantation in the United States M.P. Mullen,1,4 R.R. Thiagarajan,1,4 D. Boyer,2,4 T. Kulik,1,4 F. Fynn Thompson,3,4 G. Visner,2,4 K. Gauvreau,1,3 G. Piercey,1 C.S. Almond.1,4 1Children’s Hospital, Boston, MA; 2Children’s Hospital, Boston, MA; 3Children’s Hospital, Boston, MA; 4Harvard Medical School, Boston, MA. Purpose: Timing of lung transplantation (LT) in pediatric pulmonary hypertension (PH) remains controversial. This study examines incidence
The Journal of Heart and Lung Transplantation, Vol 29, No 2S, February 2010
Methods and Materials: Lung Preparation: Lungs were harvested from 6 adult sheep and perfused with albumin based solution via the pulmonary artery. Lungs were warmed to 37°C; ventilation initiated at 30°C; PA pressure limited to 20 mmHg; mean airway pressure limited to 25 cm H2O. Perfusion goal was 60-100 cc/kg/min for 2 hours. Quantitated Ventilation and Perfusion: A 64 MDCT scanner obtained spiral volumetric scans at total lung capacity every 40 minutes, quantifying tissue and air volumes. Perfusion flow rates were ranged from 50, 75, 100 and 125 cc/kg/min at the end of the 2 hours. Regional pulmonary blood flow (PBF) was quantified using contrast MDCT scans at each flow rate. Results: Perfusion goals were met. Tissue edema increased 9-20% in 5 lungs and decreased 3% in one lung. PVR ranged from 1-9 Wood u, Compliance ranged from 5-57 cc/ cm H2O. Non-dependent perfusion increased with flow rates. Figure 1 shows tissue edema and aeration over 2 hours.[figure1]Figure 2 shows regional perfusion with increased flow rates.[figure2]
Methods and Materials: Lungs from Yorkshire pigs were randomized into two groups: a) 0h cold ischemic time (CIT) (n⫽3) or b) 12h CIT (n⫽6) prior to EVLP. Perfusate (Steen solution, Vitrolife) L, pyruvate (P) and glucose (G) levels were measured over 12 hours. In order to assess the proportional increase in production, the L/P ratio was calculated. We subsequently measured L/P ratio in the perfusate of human lungs (n⫽12) during clinical use of EVLP and lungs rejected for clinical transplant (n⫽2) during experimental use of EVLP. Results: L/P ratio following 12h EVLP was significantly higher and the G level was lower in the 12h CIT group as compared to the 0h CIT group in pigs (Fig 1A). Rejected human lung cases had an L/P ratio at 4h EVLP that was significantly higher than the successfully transplanted EVLP human lungs (Fig. 1B).[figure1] Conclusions: L production or washout from the lung continues to occur over time in the EVLP circuit. While lungs that perform well and are successfully transplanted have some elevation in the L level, the rejected human lungs studied had significantly higher L/P ratios during EVLP. Further work is required to determine the implication of the L/P ratio and to determine its value as an EVLP marker of severity of lung injury. 284 Ex-Vivo Repair of Donor Lungs- Is Cell-Free Solution Superior to Blood Perfusion? S. Wipper,1 Y. Rittberg,1 A. Dupree,1 E. Youbert-Hubner,1 B. Reiter,1 A. Koops,2 H. Reichenspurner,1 F.M. Wagner.1 1University Heart Center Hamburg, Hamburg, Germany; 2University Hospital HamburgEppendorf, Hamburg, Germany.
Conclusions: Regional perfusion and ventilation can be quantified with MDCT imaging creating a “donor lung functional assessment tool.” 283 Lactate Production during Acellular Normothermic Ex Vivo Pig and Human Lung Perfusion T. Koike, J.C. Yeung, M. Cypel, M. Rubacha, Y. Matsuda, M. Liu, T.K. Waddell, S. Keshavjee. University of Toronto, Toronto, ON, Canada. Purpose: Serum lactate (L) is generally related to poor prognosis in disease states and used as a marker of hypoxia and poor tissue perfusion. The measured L level in serum reflects the balance between L production and metabolism. In the ex vivo lung perfusion (EVLP) circuit however, without some organs present for removal, L levels will build up over time and the significance of the specific L level is unknown. We sought to characterize L levels in damaged and healthy lungs during acellular normothermic EVLP.
Purpose: To evaluate whether ex-vivo reconditioning of donor lungs in a closed perfusion circuit using cell-free Steen-solution is superior to erythrocyte-containing solution. Methods and Materials: Perfadex preserved pig lungs were perfused in a closed-circuit (centrifugal blood-pump, heparin-coated tubing/deoxigenator, leucocyte filter) for 6hrs according to standardized protocol. Perfusion started at 21°C to reach 37°C within 30 minutes, pressure-controlled ventilation started at 32°C (FiO2⫽0,5). We compared 2 groups (n⫽6 each): Gr.1 priming with washed-erythrocytes plus Steen-solution (Hb5,0mg/dl); Gr.2 priming only Steen-Solution. Respiratory/hemodynamic parameters were documented pre-harvest and hourly during reperfusion as well as pre-/post-reperfusion wet-dry ratios. Deflation (PDI) was indexed after ventilator disconnection (1 ⫽ normal to 5 ⫽ no collaps ⫹ foamy edema), histology evaluated by semiquantitative score. Results: All lungs were successfully reperfused for 6hrs. At study endpoint 2/6 lungs in Gr.1 and 1/6 in Gr.2 showed macroscopic edema (⫽not transplantable). PDI was significantly better in Gr.2 (1.4⫾0.2 vs. 2.4⫾0.6; p⬍0.05) with correspondingly lower wet/dry ratios (4.2⫾0.2 vs. 4.8⫾0.3; p⬍0.05). Pulmonary vascular resistance was significantly lower during cell-free perfusion (Gr.2) after second hour (456⫾130 vs. 736⫾148dynes) until study end-point (570⫾194 vs.1120⫾380dynes; p⬍0.05). Pulmonary compliance and oxygenation capacity were stable and comparable between groups throughout the study (Gr.1 vs Gr.2: 43⫾7 vs. 45⫾6ml/cmH2O & 349⫾68 vs. 364⫾64mmHg; p⫽n.s.). Histology confirmed those results. Conclusions: Cell-free ex-vivo perfusion using a closed circuit reduces elevated PVR and pulmonary edema but fails to achieve 100% transplantability of lungs perfused for 6hrs. 285 Waitlist Mortality among Young Patients with Idiopathic or Famililal Pulmonary Hypertension Awaiting Lung Transplantation in the United States M.P. Mullen,1,4 R.R. Thiagarajan,1,4 D. Boyer,2,4 T. Kulik,1,4 F. Fynn Thompson,3,4 G. Visner,2,4 K. Gauvreau,1,3 G. Piercey,1 C.S. Almond.1,4 1Children’s Hospital, Boston, MA; 2Children’s Hospital, Boston, MA; 3Children’s Hospital, Boston, MA; 4Harvard Medical School, Boston, MA. Purpose: Timing of lung transplantation (LT) in pediatric pulmonary hypertension (PH) remains controversial. This study examines incidence