347

The Journal of Heart and Lung Transplantation Volume 25, Number 2S

Conclusions: Donor lung pre-treatment with endobronchial instillation of Curosurf© prior to preservation provides optimised preservation quality as compared to delayed application regimens and generally results in significantly improved functional outcome with regard to untreated controls. Additional experiments including ultrastructural surfactant analysis are now initiated to evaluate I/R-injuryspecific synthetically produced “designer”-surfactant preparations with recombinant surfactant proteins in order to further optimise modern lung preservation. 346 POLY (ADP-RIBOSE) POLYMERASE INHIBITION PROLONGS SAFE CARDIAC PRESERVATION TIMES AND IMPROVES CARDIAC FUNCTION AFTER HEART TRANSPLANTATION G. Szabo ´ ,1 N. Stumpf,1 C. Szabo ´ ,2 S. Hagl,1 1Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; 2Institue of Physiology, Semmelweis University, Budapest, Hungary Recently we showed, that the inhibition of the nuclear enzyme poly-ADP-ribose polymerase (PARP)reduces ischemia/reperfusion injury after cardioplegic arrest. In the present study, we investigated whether PARP inhibition is able to prolong safe cardiac preservation time and cardiac function in a rat heart transplantation model. Intraabdominal heterotopic transplantation was performed in Lewis rats. After 4, 8 and 24 hours of ischemic preservation, reperfusion was started after application of either saline vehicle, or PJ34 (5 mg/kg) a selective PARP-inhibitor (n⫽6/each group). Graft survival, coronary blood flow (CBF), left ventricular pressure (LVP), dP/dt, end-diastolic pressure (LVEDP), endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) were measured after one and 24 hours of reperfusion. 24h graft survival was significantly improved by PJ34 (8h preservation: 6/6 vs. 3/6 and 24h preservation: 6/6 vs. 0/6). After 4-hour preservation and 1-hour reperfusion, CBF (3.91⫾0.35 vs. 1.77⫾0.25, ml/min/g, p⬍0.05), LVP (101⫾10 vs. 67⫾8 mmHg, p⬍0.05) and dP/dt (31902⫾522 vs. 1300⫾209 mmHg/s, p⬍0.05) were significantly higher in PJ34 group in comparison to control. Vasodilatatory response to SNP was similar in both groups. ACH resulted in a significantly higher increase in CBF in the PJ34 group (71⫾8% vs. 22⫾6%, p⬍0.05). Functional differences were more pronounced between the remaining control and the PJ34 treated animals after 8 hours of preservation. Thus, PARP inhibition significantly prolongss safe cardiac preservation times and reduces myocardial and endothelial dysfunction during early reperfusion after heart transplantation. 347 N-ACETYL CYSTEINE REDUCES INFLAMMATORY TRIGGERS IN BAL FROM MICE LUNGS FOLLOWING WARM ISCHEMIA AND REPERFUSION N. Geudens,1 B. Vanaudenaerde,2 A. Neyrinck,1 F. Rega,1 C. Van De Wauwer,1 G. Verleden,2 E. Verbeken,3 D. Van Raemdonck,1 1Center for Experimental Surgery and Anaesthesiology, Catholic University, Leuven, Belgium; 2 Pneumology, Catholic University, Leuven, Belgium; 3Pathology, Catholic University, Leuven, Belgium Purpose: The warm ischemic period prior to cold preservation of non-heart-beating donor (NHBD) pulmonary grafts may increase the risk of ischemia reperfusion injury (IRI). Leukocytes and IL-1␤ are important triggers in the development of IRI. N-Acetyl Cysteine (NAC) is known to be a potent anti-oxidant. We investigated the impact of NAC on inflammatory events in Broncho-Alveolar Lavage (BAL) in a mouse model of in situ warm ischemia and reperfusion.

Abstracts

S163

Methods: Female SWISS mice were divided in 5 groups (n⫽6/group). After thoracotomy, the hilum of the left lung was clamped to induce warm ischemia (I) for 90 minutes in all groups, except in SHAM, and further unclamped in 2 study groups for 4 hours of reperfusion (I⫹R). NAC (10mg/kg, 50␮l) or Saline (50␮l) were instilled endotracheally 15 minutes before the onset of ischemia. After sacrifice, cell count and IL-1␤ levels were analyzed in BAL from the left lung. Results: (mean⫾SD) are listed in Table. There was a positive correlation between IL-1␤ levels and the number of macrophages (r⫽0.73; p⬍0.0001) as well as lymphocytes (r⫽0.63; p⬍0.0001). Group (n ⴝ 6/ group)

Total cells (*104/ml)

Macrophages Lymphocytes Neutrophils IL-1␤ (*104/ml) (*104/ml) (*104/ml)

SHAM 40.0 ⫾ 7.2 35.7 ⫾ 6.7 4.2 ⫾ 0.8 Saline⫹I 195.3 ⫾ 25.1ⴱ 151.6 ⫾ 20.3ⴱ 42.6 ⫾ 11.3ⴱ # # NAC⫹I 46.5 ⫾ 7.6 39.3 ⫾ 7.1 7.0 ⫾ 1.8# Saline⫹I⫹R 166.0 ⫾ 27.7 119.5 ⫾ 19.9 23.3 ⫾ 7.0 NAC⫹I⫹R 64.0 ⫾ 22.6§§ 53.4 ⫾ 20.0§§ 7.9 ⫾ 1.8§§

0.4 ⫾ 0.5 0.9 ⫾ 1.4 0.2 ⫾ 0.3 23.2 ⫾ 9.4 3.2 ⫾ 3.2§§

58.6 ⫾ 26.6 208.9 ⫾ 37.9ⴱ 64.4 ⫾ 13.4# 203.2 ⫾ 48.4 99.0 ⫾ 20.5§

ⴱ p ⬍ 0.001 versus SHAM; # p ⬍ 0.001 vs Saline⫹I; § p ⬍ 0.01 and §§ p ⬍ 0.001 vs Saline⫹I⫹R.

Conclusion: Administration of NAC attenuated the lymphocytic increase during ischemia and the rise in neutrophils after reperfusion. Whether there is a biochemical trigger between lymphocytes and neutrophils needs to be further investigated. Preharvest treatment with NAC could be a promising tool to reduce IRI in NHBD lung transplantation.

348 THE TECHNIQUE OF BILATERAL NATIVE LUNG SPARING LOBAR TRANSPLANTATION IN A CANINE MODEL S. Sugimoto,1 H. Date,1 R. Sugimoto,1 M. Aoe,1 Y. Sano,1 1Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan Objective: Bilateral living-donor lobar lung transplantation has become an accepted alternative to cadaveric lung transplantation. Because only lobe is implanted in each chest cavity, this procedure seems to be best suited for children and small adults. The purpose of this study was to develop a technique of bilateral native lung sparing lobar transplantation that can be applied to large adult patients. Methods: Bilateral native lung sparing lobar transplantation was performed in 6 weight-matched pair of dogs. In donor animals the right middle, lower, and cardiac lobes were separated as a right graft, and the left lower lobe was separated as a left graft. In recipient animals these 2 grafts were implanted in the both thorax after right middle, lower, and cardiac lobectomy and left lower lobectomy. Both grafts were implanted in the natural anatomic position. Function of the transplanted grafts was assessed for 3 hours after ligation of the pulmonary artery branches to the native spared lobes while the animals were ventilated with 100% oxygen. Results: Morphologic adaptation of the 2 grafts in the both thorax was found to be excellent. All 6 animals survived the assessment period with excellent pulmonary function. At the end of the 3-hour assessment period, the arterial oxygen tension was 589.0 ⫾ 14.4 mmHg, and the mean pulmonary artery pressure was 35.8 ⫾ 3.9 mmHg (Table). 30 min 60 min 120 min 180 min PaO2 (mmHg) 539.9 ⫾ 25.6 554.1 ⫾ 23.8 560.6 ⫾ 31.6 589.0 ⫾ 14.4 PaCO2 (mmHg) 40.6 ⫾ 2.2 37.5 ⫾ 2.7 37.0 ⫾ 2.0 36.6 ⫾ 2.4 Mean AoP (mmHg) 119.7 ⫾ 10.8 114.5 ⫾ 11.1 108.5 ⫾ 8.8 106.5 ⫾ 9.6 Mean PAP (mmHg) 38.4 ⫾ 3.6 33.8 ⫾ 3.2 35.8 ⫾ 3.3 35.8 ⫾ 3.9 Mean CVP (mmHg) 6.8 ⫾ 1.2 5.9 ⫾ 1.2 5.3 ⫾ 1.0 5.8 ⫾ 0.8 CO (L/min) 1.5 ⫾ 0.2 1.3 ⫾ 0.1 1.4 ⫾ 0.2 1.4 ⫾ 0.2