We assessed the histologic changes in donor and recipient bronchi from 15 dogs that had received a lung transplant and related these changes to the severity of acute rejection seen in the parenchyma of these same lungs. Minimal rejection was associated with no abnormal change in either the donor or the recipient bronchi. In mild lung rejection, mononuclear cell cuffings were seen around bronchial arteries in donor bronchial adventitia, although few mononuclear cell infiltrates were seen in the submucosa. Moderate lung rejection was associated with more prominent mononuclear cell cuffings in the donor bronchial adventitia and mucosal infiltrates of mononuclear cells in the membranous portion. In cases of severe lung rejection, the mononuclear cell infiltrates were also apparent in the cartilaginous portion of the donor bronchial mucosa. Moreover, submucosal edema and detachment of bronchial epithelium were seen. These histologic changes were not observed in the recipient bronchi during acute rejection, nor were they seen in the donor and the recipient bronchi during lung infection without rejection. They might, therefore, reflect acute rejection in the donor bronchus. These results might provide the histologic support for our previous observation of decreased bronchial mucosal blood flow measured by the laser Doppler flowmeter in relation with the extent of acute lung rejection.

Acute Disease↗

PubMedDate not supplied

Significance of bronchial mucosal blood flow for the monitoring of acute rejection in lung transplantation.

Bronchial mucosal blood flow (BMBF) was measured with a laser-Doppler flowmeter in a canine model (n = 20), and the measurement was evaluated to see if it was a useful method for diagnosing allografted lung rejection. The ratio of the value of BMBF at the level of the donor second carina against that at the level of carina (the L/C ratio, an index of BMBF of donor bronchus) decreased in accordance with the extent of lung rejection, and it increased and entered the normal range with the reversal of lung rejection. Compared with the L/C ratio and the rejection grade by histologic changes in open-lung biopsy, the L/C ratio at grade 0 (latent phase) was 0.91 +/- 0.07; at grade Ia (early vascular phase), 0.86 +/- 0.05; at grade Ib (late vascular phase), 0.68 +/- 0.10; at grade II (early alveolar phase), 0.60 +/- 0.14; and at grade III (late alveolar phase), 0.50 +/- 0.15. A significant difference was noted between grades Ia and Ib (p less than 0.01) and between grades Ib and III (p less than 0.01). The sensitivity and the specificity in the detection of early rejection before grade Ib were 96% and 92%, with only one false-negative and two false-positives resulting from 51 measurements of BMBF. In three cases of serious lung infections, the L/C ratio did not fall, and the rejection could be distinguished from infection. These results suggest that measurement of the BMBF is useful for detecting the early rejection of transplanted lungs.

Animals↗

PubMedDate not supplied

New diagnostic method for pulmonary allograft rejection by measurement of bronchial mucosal blood flow.

We investigated the relationship between the rejection of lung allografts and the bronchial mucosal blood flow with a laser flowmeter. Nineteen mongrel dogs underwent left lung allotransplantation and were given daily oral immunosuppressive therapy with azathioprine and cyclosporine. The bronchial mucosal blood flow at the carina and the bifurcation of left upper and lower bronchi were measured on days 14, 21, and 28 after left lung transplantation. The bronchial mucosal blood flow of the transplanted lungs was expressed as the ratio of bronchial mucosal blood flow at the bifurcation of left upper and lower bronchi to the bronchial mucosal blood flow at the carina (L/C ratio) instead of the absolute value because bronchial mucosal blood flow was affected by the depth of anesthesia of the dogs. We classified the histologic appearance of the transplanted lung tissue into one of five grades: 0, 1a, 1b, 2, and 3. No rejection was in grade 0, and as the rejection process progressed the higher grades were used in order. The mean L/C ratios for grades 0, 1a, 1b, 2, and 3 were 0.95 +/- 0.03, 0.82 +/- 0.05, 0.68 +/- 0.04, 0.58 +/- 0.07, and 0.30 +/- 0.07, respectively. Thus the L/C ratio decreased as the rejection process progressed. The histologic changes of the donor main bronchus in each rejection grade were investigated. Mononuclear cell infiltration and edema around the small vessels was seen in early rejection. These same histologic changes appeared in muscular arteries as rejection progressed, and the damage to the small vessels and muscular arteries was more severe in late rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Effects of inhaled nitric oxide in single lung transplantation in rats with monocrotaline-induced pulmonary hypertension.

BACKGROUND: The edema of grafted lungs during the early postoperative period is one of the serious complications of single lung transplantation for primary pulmonary hypertension. METHODS: The effectiveness of inhaled nitric oxide in single lung transplantation for primary pulmonary hypertension during the early postoperative period was evaluated with the use of rats with monocrotaline-induced pulmonary hypertension. In the inhaled nitric oxide group, rats were given 60 parts par million of nitric oxide for 24 hours just after left lung transplantation; in the no inhaled nitric oxide group, rats were kept without nitric oxide inhalation; in the control group, normal rats received left isografts. RESULTS: Three hours after transplantation, the mean pulmonary artery pressure of the no inhaled nitric oxide group (28.0 +/- 4.6) was significantly higher than that of the control group (23.3 +/- 0.9, p < 0.05) and the inhaled nitric oxide group (22.7 +/- 1.7, p < 0.05). On the first postoperative day, the mean left-to-right pulmonary blood flow ratio in the inhaled nitric oxide group was 0.34 +/- 0.03; it showed no significant difference to those of the other two groups, whereas that of the no inhaled nitric oxide group (0.42 +/- 0.14) was significantly elevated compared with that of the control group (0.14 +/- 0.03, p < 0.05). Histopathologically, the edema of the grafted lungs 24 hours after operation in the inhaled nitric oxide group was less severe than that in the no inhaled nitric oxide group. CONCLUSIONS: The postoperative use of inhaled nitric oxide is effective to reduce the pulmonary edema of the grafts in single lung transplantation for pulmonary hypertension by reducing acute pulmonary blood flow shift toward grafts after transplantation.

Administration, Inhalation↗