The uterine circulation in toxemia.
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The inhibition of Clostridium perfringens alpha-toxin by ethylenediaminetetraacetate (EDTA) and diethylenetriaminepentacetate (DTPA) was studied utilizing three different in vitro assay procedures: diffusion on egg yolk-agar, disintegration of muscle sections, and manometric assay with partially purified lecithin as substrate. DTPA was 10 to 20 times more efficient as an inhibitor than EDTA in systems containing relatively large amounts of calcium; these observations were similar to those observed in previous in vivo protection studies. A number of other chelating agents were tested for their ability to inhibit alpha-toxin in vitro and protect mice against it; the chelating agents which were the most efficient in vitro inhibitors had the greatest in vivo protective ability.
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A toxin isolated from Group B beta-hemolytic streptococci, Type III was infused into adult sheep and newborn lambs. A two-phased reaction was observed. There was an initial phase of pulmonary hypertension and high flow of protein-poor lymph. This was followed by a second phase when pressures returned to baseline but lymph flow remained twice the baseline values and protein concentration in lymph increased. During the second phase there was a significant increase in lymph protein clearance, suggestive of increased microvascular permeability to protein. The absolute granulocyte count decreased to 10% of baseline values by 60 min after the infusion, and was followed by a variable return to baseline. The sheep with the largest changes in protein clearance were those who had the slowest return to baseline values. Pathologic examination of lung tissue revealed there was capillary dilation, interstitial edema, and large numbers of granulocytes in the lungs. The basement membranes of both capillaries and arterioles showed disruption and widening, along with fragmentation of the internal elastic membrane. This study provides morphologic and physiologic evidence of increased pulmonary vascular permeability after injection of streptococcal toxin associated with granulocyte trapping in the lung. We postulate that granulocytes may be involved as mediators of the pulmonary vascular injury.