McLarty, Allison J.

Experiments were designed to determine how changes in the ratio of specific vascular endothelium-derived factors might affect reactivity of bronchial smooth muscle. The epithelium was mechanically removed from rings of third-order canine bronchi, and the rings were suspended in organ chambers for measurement of isometric force. Rings of pulmonary artery were cut; in some the endothelium was mechanically removed. The arterial rings were everted and pairs, with and without endothelium, were incubated with control solution, NG-monomethyl-L-arginine (L-NMMA), indomethacin, or both L-NMMA and indomethacin for 90 min. They were then inserted into the lumen of the bronchial rings. Cumulative concentration-response curves to acetylcholine and 5-hydroxytryptamine were obtained. There was no significant difference in response between bronchi containing arteries with or without endothelium incubated with control solution. Contractions of bronchi containing arteries without endothelium, incubated in either L-NMMA or indomethacin, increased from control. However, in rings containing arteries with endothelium, incubation with either inhibitor decreased bronchial contractions. Incubation with both inhibitors eliminated the difference. These results suggest that the vascular endothelium produces factors that can both contract and relax bronchial smooth muscle. With inhibition of production of either nitric oxide with L-NMMA or prostanoids with indomethacin, release of other endothelium-derived factors occurs that attenuates contractions of bronchial smooth muscle. Therefore, an imbalance in the ratio of production of endothelium-derived factors may contribute to bronchospastic disorders.

Background Experiments were designed to define cardiac function in dogs with single lung allografts during acute rejection of the allografted lung. Methods and Results Left lungs were either autotransplanted (n=4) or allotransplanted (n=8) in adult male mongrel dogs. All allotransplanted animals were maintained on triple-drug immunosuppression (cyclosporine, azathioprine, and steroids) for 5 days after the operation. In 4 allotransplanted animals, treatment was discontinued, allowing the animals to reject (usually after a further 3 days; rejecting group); 4 other allotransplanted animals were maintained on immunosuppression for an additional 3 days (immunosuppressed group). Another group of dogs were not operated on but were maintained on the same immunosuppression as the rejecting group (controls). All experimental animals underwent fast computed tomographic scanning with measurement of left ventricular pressure and calculation of ventricular chamber volumes, cross-sectional areas of coronary arteries, myocardial perfusion, and intramyocardial blood volume. Neither cardiac output, left ventricular mass, left ventricular pressure, nor myocardial oxygen consumption was altered during acute rejection of lung allografts. However, left ventricular contractility (systolic elastance, E max ) and ejection fraction were depressed to approximately one half ( P <.05) in acutely rejecting animals compared with other groups. The cross-sectional area of the coronary arteries was less in autotransplanted and allotransplanted treated animals than in animals that were not operated on. Cross-sectional area of the coronary arteries was decreased by an additional 30% in the rejecting group ( P <.05). Conclusions The results of this study indicate that acute rejection of a single lung allograft decreases cardiac performance and reduces diameter of coronary arteries in the recipient. Alterations of circulating humoral factors and activated leukocytes may contribute to these changes.