DONOR PRETREATMENT WITH INTRAVENOUS PROSTACYCLIN VERSUS INHALED NITRIC OXIDE IN EXPERIMENTAL LUNG TRANSPLANTATION1

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Abstract
The pulmonary vasodilatory effects of prostacyclin (PGI2) were compared with inhaled nitric oxide (NO) for donor treatment in an acute double lung transplantation model in the rat. The PGI2 group (n=10) received 35 microg/kg PGI2 both intravenously and into the flush solution. The NO group (n=10) was ventilated before and during perfusion with nitric oxide for an expiratory NO concentration of 20 ppm. Both groups were compared with untreated controls (n=10). Following cold ischemia of 16 hr the donor lungs were implanted in syngeneic recipients via specially designed stents to the left pulmonary artery and vein. Separate graft ventilation permitted determination of compliance and resistance. During 120 min of reperfusion serial measurements of graft pulmonary vascular resistance (PVR) and alveolar arterial oxygen difference (AAD02) were obtained. Final graft assessment included weight gain and histological analysis. Data are listed as mean+/-SE. The type of donor pretreatment had a definite and negative impact on survival (NO: 106+/-6, controls: 116+/-4, PGI2: 120+/-0 min; P<0.02) and overall graft function. During reperfusion the compliance was significantly reduced in NO (23+/-4) in comparison with controls (34+/-3) and PGI2 (50+/-4 ml/cmH2O; P<0.01). The PVR was 785+/-238 in NO, 240+/-60 in controls and 181+/-71 mmHg/ml/min in PGI2 (P<0.02). The AaD02 was compromised in NO (486+/-44) compared with controls (396+/-53) and PGI2 (108+/-34 mmHg; P<0.02). The weight increase at the end of reperfusion amounted to 101+/-17% in NO, 98+/-13% in controls, and 69+/-7% in PGI2 (P<0.05). Histological analysis showed significantly more interstitial edema in the NO group. In conclusion, PGI2 administration significantly improves global lung function while the inhalation of nitric oxide before and during donor perfusion has a detrimental effect on the quality of graft preservation.