| Objective: To study the protective effects of ischemic preconditioning to the lung injury during isolated lung perfusion with chemotherapeutic agents.Methods : Part I : twelve pigs were randomly divided into two groups: control group (Group C) and ischemic preconditioning group (Group IP).Each group had 6 pigs. Pig's ages ranged from 3.1 to 3.6 months in control group and from 3.2 to 3.7 months in IP group. Pig's mean weight were 36.90 4.71 kg in Group C and 35.38 5.12 kg in Group IP. Part II: From October 2000 to September 2002, Thirty patients with advanced unresectable cancer or metastatic sarcomas to the lung underwent isolated single lung perfusion with doxorubicin. Thirty patients were randomly divided into two groups: control group (Group C) and ischemic preconditioning group (Group IP). Each group had fifteen patients. Patients' ages ranged from 35 to 67 years in control group and from 34 to 72 in IP group. Group C was performed isolated lung perfusion with doxorubicin in Part I and Part II. Group IP was performed ischemic preconditioning during lung isolated perfusion with doxorubicin in Part I and Part II. Ischemic preconditioning on lung means left pulmonary artery is clamped for 10 minutes then released for 15 minutes. The model of isolated single lung perfusion was that a perfusion catheter was inserted in the left pulmonary artery, a venous drainage cannula was placed in the pulmonary vein, and both catheters were connected to the heart pump. The lung or lobe were totally isolated and then perfused with doxorubicin. The initial perfusate concentration of doxorubicin was 6u.g/ml in perfusating volume. The isolated lung perfusion was performed for 45 minutes at 200-300 ml/min at a mean pulmonary artery pressure of 10-25mmHg and followed by a 5-minute washout with 2:1ACD solution at a rate of 200ml/min. We monitored the MPaP and PVR by Swan-GanZ catheter in pre-and postperfusion. The PAP was measured atpre-and postperfusion. Blood samples were collected from the perfusion circuit at 15 min intervals during isolated perfusion for doxorubicin levels. Peripheral blood samples were obtained pre-and postperfusion for arterial blood gas analysis and check for SOD and MDA. Systemic blood samples to check for drug leakage were also collected during and after the isolated perfusion. Lung biopsies of left upper, lower lodes were performed immediately following perfusion and one hour postperfusion for histologic examination, at the meantime the wet/dry ratio was measured. We assess the ICAM-1 expression by immunohistochemical analysis with envision method using biopsy samples that had been snap frozen and stored at -80 . We analyzed the mRNA expression of 1C AM-1 by RT-PCR using the sample as described above. Results ( in Part I and Part II):1.The MPaP, PVR and PAP after ILP in group IP were much lowerthan those in group C (P<0.05). 2.The PaO2 after ILP in group IP was much higher than that in groupC(P<0.01). 3.The SOD in group IP after ILP was much higher than that in groupC(P<0.01).The MDA in group IP after ILP was much lower than that ingroup C(P<0.01).4. The w/d ratio of lung after ILP in group IP is much lower than thatin group C(P<0.01)5. The lung histologic examination after ILP have shown thatgroup C were significantly more serious than group IP in pulmonary edema, inflammatory cell infiltration, mild focal hemorrhage and alveolar disruption.6. Part I :The expression of ICAM-1 of lung tissue was obviouslydecreased in group IP than that in group C by immunohistochemisty with envision method. The expression of ICAM-1 mRNA of lung tissue was significantly lower in the group IP compared to the group C by reverse transcriptionpolyerase chain reaction.(RT-PCR) (P<0.01).7. Part II :There were no hospital deaths in group C and in group IP.The complications included hypovolemia shock and acute lung injury. The mean hospital stay was 12.5days in group C, and 8.5 days in group IP. Following up of 6 months to 24 months, we found the masses were dimini... |
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