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.
Based on the known properties of ambroxol and dexamethasone to inhibit inflammation and increase endogenous surfactant levels, the potential advantage of donor pretreatment with either drug was investigated in an acute rat double-lung transplant model. Donor animals were randomly assigned to one of three treatment groups: an ambroxol group (AMB; 0.4 mg/kg), a dexamethasone group (DX; 2 mg/ kg); or an untreated control group (CN). Drugs were given intraperitoneally 6 h prior to harvest. Following standard preservation and 16 h of cold ischemia, the donor double lung block was implanted into syngeneic recipients using custom-designed stents for the vascular anastomosis. During reperfusion, serial measurements of graft pulmonary vascular resistance and alveolar-arterial oxygen difference were obtained. Separate graft ventilation allowed determination of graft dynamic lung compliance. Final assessment included weight gain and histology. For phospholipid analysis, lung lavages were performed in the three study groups at the end of reperfusion and compared to levels before graft harvest. Donor pretreatment did not significantly affect preharvest phospholipid levels. Survival following graft ischemia and reperfusion was shortest after AMB (92 + 5 min) and longest after DX (110 * 5 min; DX vs AMB P < 0.03) and CN (116 k 4 min; CN vs AMB P < 0.02). DX pretreatment provided better compliance ( P < 0.02) and lower vascular resistance ( P < 0.0001) than AMB treatment. Airway resistance was lower in the AMB and DX groups than in controls ( P < 0.04 and P < 0.02, respectively). The alveolar-arterial oxygen difference was markedly similar in all groups. Graft weight gain amounted to 114 % + 10 % in AMB, 88% ? 12% in DX, and 98% * 13 % in CN ( P = NS). Thus, in this rat lung transplantation model, donor pretreatment with dexamethasone did not improve graft function compared to untreated controls and donor pretreatment with ambroxol was found to be potentially detrimental to graft function during reperfusion.
Based on the known properties of ambroxol and dexamethasone to inhibit inflammation and increase endogenous surfactant levels, the potential advantage of donor pretreatment with either drug was investigated in an acute rat double-lung transplant model. Donor animals were randomly assigned to one of three treatment groups: an ambroxol group (AMB; 0.4 mg/kg), a dexamethasone group (DX; 2 mg/ kg); or an untreated control group (CN). Drugs were given intraperitoneally 6 h prior to harvest. Following standard preservation and 16 h of cold ischemia, the donor double lung block was implanted into syngeneic recipients using custom-designed stents for the vascular anastomosis. During reperfusion, serial measurements of graft pulmonary vascular resistance and alveolar-arterial oxygen difference were obtained. Separate graft ventilation allowed determination of graft dynamic lung compliance. Final assessment included weight gain and histology. For phospholipid analysis, lung lavages were performed in the three study groups at the end of reperfusion and compared to levels before graft harvest. Donor pretreatment did not significantly affect preharvest phospholipid levels. Survival following graft ischemia and reperfusion was shortest after AMB (92 + 5 min) and longest after DX (110 * 5 min; DX vs AMB P < 0.03) and CN (116 k 4 min; CN vs AMB P < 0.02). DX pretreatment provided better compliance ( P < 0.02) and lower vascular resistance ( P < 0.0001) than AMB treatment. Airway resistance was lower in the AMB and DX groups than in controls ( P < 0.04 and P < 0.02, respectively). The alveolar-arterial oxygen difference was markedly similar in all groups. Graft weight gain amounted to 114 % + 10 % in AMB, 88% ? 12% in DX, and 98% * 13 % in CN ( P = NS). Thus, in this rat lung transplantation model, donor pretreatment with dexamethasone did not improve graft function compared to untreated controls and donor pretreatment with ambroxol was found to be potentially detrimental to graft function during reperfusion.
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