To test the hypothesis that the broad spectrum protease inhibitor, aprotinin, can prevent early pathophysiology of sepsis, we administered endotoxin (0.1–0.75 μg/kg) by a 30-min infusion to awake goats. Animals were used as their own controls receiving endotoxin with no treatment on one day and treatment with a bolus injection (10 trypsin inhibitory units, TIU, per kg) followed by a 6-hr infusion (5 TIU/kg/hr) of aprotinin on another. The effect on systemic and pulmonary hemodynamics, lung lymph flow (QL), lymph plasma protein ratio (L/P), and systemic eicosanoid levels were assessed. QL quickly reached 28 ml/hr (four times baseline) in both groups then slowly returned toward baseline. L/P ratio of both groups decreased by about 10% then returned to baseline. QL and L/P were not different between groups. Likewise, vascular parameters were not different between groups. Mean pulmonary artery pressure increased approximately 150% to a peak of 58 cm H2O in both groups while pulmonary artery wedge pressure doubled from a baseline of 8 cm H2O then both groups returned to baseline. Systemic arterial pressure decreased over the 6 hr experimental period by 15 Torr to 70 Torr in both groups. Cardiac output declined from 4.3 to 3 liter/min after the endotoxin, remaining at that level for 2 hr then progressively increased to about 5 liter/min in both groups. We conclude that aprotinin, in doses similar to those reported to give protection from acute lung injury of various origins, fails to modify the early cardiopulmonary pathophysiology of endotoxin.

The enormous destructive power of present stocks of nuclear weapons poses the greatest threat to public health in human history. Technical changes in weapons design are leading to an increased emphasis on the ability to fight a nuclear war, eroding the concept of deterrence based on mutually assured destruction and increasing the risk of nuclear war. Medical planning and civil defence preparations for nuclear war have recently been increased in several countries although there is little evidence that they will be of significant value in the aftermath of a nuclear conflict. These developments have raised new ethical dilemmas for those in health professions. If there is any risk of use of weapons of mass destruction, then support for deterrence with these weapons as a policy for national or global security appears to be incompatible with basic principles of medical ethics and international law. The primary medical responsibility under such circumstances is to participate in attempts to prevent nuclear war.

We have attempted to determine the membrane parameters, permeability-surface area product (PS) and reflection coefficient (sigma), necessary to describe solute exchange in the pulmonary circulation. Experimental lymph-to-plasma ratios were obtained for total protein (Rtot) and albumin (Ralb) using lung lymph collected from goats with chronic lung lymph fistulae. Lymph flow (QL) and solute flow (QS) were varied by increasing microvascular pressure in a stepwise manner by inflating a balloon in the left atrium. The increased QL and decreased Ralb from multiple experiments in four goats were used to plot PS vs. sigma using the equation of Patlak et al. (J. Theor. Biol. 5: 426-442, 1963). The region of intersection of two or more such curves should identify the two membrane constants. However, these curves rarely intersected suggesting that perhaps the lung barrier was not adequately represented by a single homoporous membrane. To evaluate heteroporosity, the three-pore model of Blake and Staub (Microvasc. Res. 12: 197-220, 1976) was investigated. By use of their pore sizes and relative pore distributions, values for the fluid filtration coefficient, PS, and sigma of each pore type were calculated, and finally QL and R were predicted at various microvascular pressures. When these calculated values of QL and R were plotted using the equation of Patlak et al., an equivalent homoporous PS and sigma could still be found. Therefore, a heteroporous membrane does not appear to explain the failure of our data plots to intersect. Possible alternative models are suggested.