Flow-induced pressure differentially regulates endothelin-1, urotensin II, adrenomedullin, and relaxin in pulmonary vascular endothelium.

We hypothesized that increased pulmonary vascular pressure--one of the characteristics of congestive heart failure--directly regulates pulmonary endothelial vasoconstrictors (endothelin-1, urotensin II) and vasodilators (adrenomedullin, relaxin). To this end, we subjected pulmonary artery endothelial cells in a novel flow-chamber model to different shear stresses (17, 29, and 46 dyn/cm(2)) at low and elevated levels of downstream pressure (10 and 30 mm Hg). Application of elevated pressure over 16 h increased gene expression and peptide secretion of endothelin-1 at all shear levels, whereas secretion of adrenomedullin rose via decreased expression of its clearance receptor. In contrast, preprourotensin II mRNA and urotensin II peptide decreased in response to elevated pressure, and relaxin remained unaffected. This is the first study to identify pressure as key regulator of mediator synthesis by pulmonary vascular endothelium. Pressure-induced mediator regulation may represent an early event in the development of secondary pulmonary hypertension.

Biostability of polyurethanes.

Aside from the medical requirements a material has to fulfill to qualify as biocompatible, for the bioengineer, who is involved in the design, construction and fabrication of prosthetic devices, the mechanical, physical and chemical properties of the material as well as its possible manufacturing procedures and, last but not least, its biostability are of the same importance. In the very aggressive biological environment, the material should behave inertly, showing no surface erosions, molecular chain disruptions, uptake of low molecular weight biological materials, local chemical imbalances, tendency to calcification or negative changes of mechanical properties. With regard to this aspect, different polyurethanes have been evaluated in-vitro and in-vivo as basic materials and already fabricated devices (blood pumps and heart valves). The comparison of the results stresses the necessity of further efforts to achieve a standardized test protocol for the prove of the biostability of polymers, containing appropriate, well-defined in-vitro and in-vivo test methods to establish the necessary data basa for the materials' clinical approval.

Development and in vitro fatigue testing of a new bloodpump.

1. Three different types of blood pumps (LVAD 80 ml, LVAH 100 ml, TAH 1 120 ml, TAH r 100 ml) with two variations had been designed, fabricated and fatigue tested. 2. The optimizing of the blood diaphragm thickness by analyzing the results of the fatigue testing was impossible up to now because of the long functional times of pumps even with very thin diaphragms (50-80 microns). 3. First in vivo experiments showed no problems with the blood compatibility, the anatomical fit, the fixation of the valves and the toxicity of the used combination of materials. There was no pump related termination in LVAD as well as in TAH experiments.

New methods for the in vitro investigations of the flow patterns in artificial hearts.

With the 3 applied methods one can investigate and obtain most of the interesting aspects of the flow within blood pumps: an integral picture of the flow, the development and position of stagnation flow, the time course of the velocity in points of special interest, the turbulence, and an integral picture of the mean boundary layer flow. The measurements have shown that the flow in the blood pumps is turbulent, the turbulence can be considered harmless, because its intensity is much weaker than that of a valve; there is a correspondence between the hotfilm method and the dye-washout method, and that there is a correspondence between the dye-washout method and the in vivo clot formation. Pumps, which have been designed according to these measurements, have been implanted in a series of calves. The pumps now have a smooth continuous inner surface and usually show no thrombus formation at all (anticoagulants are used) at the postmortem. Some animals do very well, such as the one in Figure 16 during his daily walk of 500 M on the treadmill. The animal is in its 45th day of survival and remains well to date.