Reimplantation response in isografted rat lungs. Analysis of causal factors.

The function of transplanted lungs may be critically impaired in the early postoperative period by the reimplantation response. Several factors of the transplantation procedure, such as disruption of hilar structures (hilar stripping), stenotic anastomoses, and graft ischemia, are considered to cause this reimplantation response. In this study the individual contributions of these factors have been analyzed in rats, after isogeneic transplantation or hilar stripping of left lungs. Marck's technique for orthotopic transplantation of the left lung in rats was refined so that an 85% postoperative survival rate was achieved. Transplanted and hilar-stripped lungs were investigated by lung perfusion scintigraphy and chest roentgenography at regular intervals up to 168 days after operation. Macroscopic and histologic morphology was examined at corresponding intervals. Our results show that perfusion and ventilation of lung grafts are independently affected by distinct factors of the transplantation procedure. Hilar stripping did decrease graft perfusion transiently. Permanent decrease of perfusion was found to be caused by stenosis of the anastomosed pulmonary artery. Hilar stripping also impaired ventilation, by causing interstitial and alveolar edema. After transplantation, edema and consequent impairment of ventilation were aggravated by graft ischemia, proportionally to its duration. Our improved technique for transplantation of left lungs in rats provides a new opportunity for investigating the immunologic problems of lung transplantation.

Polyploidy in the pancreas of the normal and diabetic mutant mouse.

The DNA content of endocrine and exocrine pancreatic nuclei of normal C57BL/KsJ and diabetic mutant C57BL/Ks-db/db mice was measured by Feulgen microdensitometry. The exocrine and endocrine pancreatic nuclei of the 4-week-old normal, 12-week-old normal, and 4-week-old (prehyperglycaemic) diabetic mutant mice contained diploid and tetraploid cells, while the 12-week-old (established hyperglycaemic) mutant contained diploid, tetraploid, and octaploid nuclei. The polyploidy in the endocrine pancreas of all these mice was confined to the B-cells, while the A-cells were always diploid.

Pathogenesis of Pseudomonas aeruginosa pneumonia during immunosuppression.

A guinea pig model of immunosuppression was utilized to study the effects of immunosuppressive chemotherapy on lung response to challenge with Pseudomonas aeruginosa. Study groups included normal guinea pigs, as well as guinea pigs that received a one-week course of cortisone acetate (CA, 100 mg/kg per day) plus 15 mg of cyclophosphamide (CTX)/kg per day (CA + LoCTX group) or 30 mg of cyclophosphamide/kg per day (CA + HiCTX group). Separate groups received CA or HiCTX alone. Intratracheal instillation of P. aeruginosa resulted in bilateral hemorrhagic pneumonia in both normal and immunosuppressed animals. Survival was 100% for normal animals and for those given CA alone, 67% in the CA + LoCTX and the HiCTX groups, and 0 in the CA + HiCTX group. Increased mortality correlated with a diminished polymorphonuclear leukocyte inflammatory response in infected lung tissues and also with the addition of CA to CTX. Clearance of viable P. aeruginosa from lung tissue was significantly reduced in animals receiving the combination CA + HiCTX. Thus, decreased lung inflammation and the addition of CA appeared to be important determinants for fatal pseudomonas pneumonia.

Host defense mechanisms against pneumonia due to Pseudomonas aeruginosa.

Pneumonia due to Pseudomonas aeruginosa is associated with unusually high mortalities. Accordingly, efforts to define better the most important components of lung defenses against this infection are justified as a prelude to defining improved management strategies. In this report, a guinea pig model of experimental aspiration pseudomonas pneumonia was employed for studies of cellular and humoral mechanisms of pulmonary defense. Animals treated with cortisone acetate plus cyclophosphamide experienced decreased survival from pneumonia, and survival rates correlated directly with the degree of myelosuppression. Numbers of pulmonary macrophages and polymorphonuclear neutrophils were reduced in drug-treated animals before impairment of macrophage antibacterial function. Thus, a reduction in numbers of phagocytes alone was sufficient to markedly reduce lung defenses. In additional experiments, normal guinea pigs were vaccinated with a lipopolysaccharide pseudomonas vaccine. Improved survival from pneumonia correlated with high titers of type-specific, heat-stable opsonic antibody. It is concluded that adequate numbers of lung phagocytes, plus type-specific opsonic antibody, represent the ideal status for lung defense against P. aeruginosa infection.

Transbronchial lung biopsy in the compromised host.

Thirty-eight immunocompromised patients underwent transbronchial lung biopsy via the fiberoptic bronchoscope as part of a diagnostic evaluation for fever and roentgenographic evidence of a new pulmonary infiltrate. Diagnostic information was obtained from lung biopsy in 29 patients (76%), with infection accounting for ten cases and a nonspecific interstitial pneumonitis in 13 patients. Concomitant bronchial brushings were diagnostic in only three patients (all with infections). Diffuse roentgenographic infiltrates were expecially amenable to bronchoscopic lung biopsy diagnosis (84%), while in localized infiltrates, there was only a 43% diagnostic yield. Although thrombocytopenia and hypoxemia were common in these patients, morbidty was low (four patients had pneumothoraces with no noteworthy bleeding) and there were no deaths resulting from this procedure. Prebiopsy platelet transfusions were used in five patients with severe thrombocytopenia (platelet cound, less than 50,000/cu mm). The diagnostic efficiency and low morbidity associated with transbronchial lung biopsy indicate that this procedure can safely play a role in the evaluation of pneumonia in the compromised host.