Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis--Wisconsin. / Vita. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 53-57).

No description available.

Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids-such as catheter-related infections and intolerable adverse effects-may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients transitioning from parenteral prostanoids to inhaled trepostinil. Rigid inclusion criteria were used, including parenteral prostanoid dose < 30 ng/kg/min, New York Heart Association functional class (FC) < 3, and pulmonary vascular resistance (PVR) < 6 Wood units. Of the 9 patients meeting initial inclusion criteria, 3 were excluded. In the remaining patients, the parenteral prostanoid was reduced and the inhaled prostanoid was increased over 24-36 hours with continuous hemodynamic monitoring. Exercise capacity and FC were measured at baseline and weeks 1, 4, and 12. All patients were successfully weaned from parenteral prostanoids. An acute PVR decrease was seen with most inhaled prostanoid doses, but PVR varied throughout the transition. Patients tolerated inhaled prostanoids for 9-12 breaths 4 times a day with no treatment-limiting adverse events. At week 12, FC was unchanged, and all patients continued to receive inhaled prostanoids without serious adverse events or additional PAH therapy. In 5 of 6 patients, 6-minute walk distance and peak VO2 were within 10% of baseline. Using a strict transition protocol and rigid patient selection criteria, the parenteral prostanoid to inhaled prostanoid transition appeared safe and well tolerated and did not result in clinical deterioration over 12 weeks. Hemodynamic variability noted acutely during transition in our study did not adversely affect successful transition.

In spite of the extreme thinness of the avian pulmonary blood-gas barrier (PBGB), it is remarkably strong. To understand the basis of the remarkable strength of the avian PBGB, network of collagen connective tissue that form the lung’s parabronchial fibrous framework and type-IV collagen, a principal component of the basement membrane was investigated in the BGB and in the epithelial-epithelial contacts between the air capillaries in the domestic fowl, Gallus gallus variant domesticus. Techniques of discriminatory staining, selective alkali digestion, vascular casting followed by alkali digestion and immunoelectron microscopy were used. Abundant collagen fibers of the interparabronchial septa, which form part of the tunica adventitia of the interparbronchial vessels, firmly interconnect adjacent parabronchi directly and indirectly (via intraparabronchial vessels). Peripherally, the intraparabronchial artery, with its tunic of collagen fibers, enters and penetrates the exchange tissue mantle. The collagen fibers around the vessel decrease in quantity as it divides into blood capillaries. From the luminal side, the projection of the parabronchial lumen into the exchange tissue mantle as the atria, the infundibulae and the air capillaries, in this order, carry collagen covering which reduces in quantity with each division. The three-dimensional interactions between blood capillaries from the peripheral part and air capillaries from the central lumen allow contact formation between blood capillaries, air capillaries and between air- and blood capillaries. Collagen fiber continuum starting from the interparabronchial septa runs through the exchange tissue by following the three contacts sites and terminates at the parabronchial lumen. At the periphery, the collagen fibers constitute a conspicuous bundle. Within the exchange tissue mantle, the collagen forms diffuse complex interconnections of thin fibers. Towards the parabronchial lumen and within interatrial septa, the thinner collagen fibers of the exchange tissue mantle aggregate to form thick bundles which bind to the connective tissues surrounding the parabronchial muscles. Based on the structural arrangements and function of the smooth muscle, the collagen- and the elastic tissue fibers, and structures like the interparabronchial septa and their associated blood vessels, it was envisaged that: dynamic- tension and compressive forces exist in a parabronchus to form a tensegrity (tension integrity) system. The tensegrity arrangement imparts rigidity to a parabronchus while strengthening the air and the blood capillaries. Mechanical interdependence between parabronchi and between air- and blood capillaries allows efficient transmission and redistribution of tension. The tortuous course of the collagen fiber continuum that follows the three-dimensional intertwining of the gas exchange units- from septa to the lumen- ensures that tension does not travel a straight course and as such, any extrinsic or intrinsic force applied to the structure is transmitted away from the point of origin. Graded exercise intensities and perfusion at different pressures on the integrity of the BGB were used to determine the condition under which the blood-gas barrier in the avian lungs fails. Number of red blood cells and protein concentration in the harvested lung lavage fluid were estimated in the exercised chickens. For histological analysis, numbers of epithelial-epithelial (E-E) breaks and blood-gas barrier (BGB) breaks were counted in each of the four vascular regions of the lung in both the exercised and the perfused lungs. Post exercise blood lactate analysis showed a 4-fold increase between rest and maximal exercise (2.95 m/s) while the numbers of red blood cells and protein concentration increased steadily with increasing exercise intensity, however, the degree of increments appeared to decrease at higher workloads. The two kinds of breaks occurred at all levels of exercise and in the resting birds but at any exercise intensity, there were more E-E breaks than BGB breaks. The numbers of breaks increased with increasing exercise intensity and the difference between the two types of breaks decreased with increasing exercise intensity. In resting birds, there were no breaks in the area of the lung supplied by the cranial branch of the PA. In the exercised birds, differences in number of blood-gas barrier breaks among the four vascular territories only occurred at 0.66 m/s where the lowest and highest counts occurred in the cranial- and caudomedial regions respectively, whereas at all other levels of exercise, the numbers of breaks were comparable. Presence of red blood cells in the lungs of resting birds indicated that failure of the blood-gas barrier might be a common but inconsequential event in the avian lung. A positive linear relationship exists between the perfusion pressure and the numbers of both E-E and blood-gas barrier breaks. At all perfusion pressures, there are more E-E breaks than BGB breaks. The difference between the two types of breaks decreased with increasing pressure. At any perfusion pressure, more breaks occurred in the regions supplied by the accessory- and caudomedial branches of the PA than in the regions supplied by the cranial- and the caudomedial ones. This could be because the pressures in the two blood vessels may be higher since the caudomedial branch is the most direct continuation of the PA while the accessory branch is the narrowest and the first to originate from the PA. Because of the extreme thinness of the blood-gas barrier and unavoidable puncturing of air sac when the thorax is accessed to cannulate the pulmonary vessels, the exact pressure at which the BGB fails could not be ascertained since both types of failure occurred at all perfusion pressures. However, separation of the epithelial-epithelial contacts, caused by distension of the blood capillaries, started appearing at the perfusion pressure of 2.89kPa. This may represent the pressure at which the blood-gas barrier starts to fail.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 232-249).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1972. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographies.