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Proceedings of the Fifty-Eighth Annual Meeting of the American Society for Clinical Investigation, Inc., Held in Atlantic City, N.J., May 2, 1966: Abstracts J Clin Invest. 1966;45(6):980-1037. https://doi.org/10.1172/JCI105414. Research Article Find the latest version: https://jci.me/105414/pdf ABSTRACTS Comparison of Effects of Alpha Adrenergic Blockade luminescence. Inhibition of ATPase activities by ouabain, on Resistance and Capacitance Vessels. FRANCOIS parachloromercuribenzoate (PCMB), and parachloro- M. ABBOUD * AND JOHN W. ECKSTEIN,* Iowa City, mercuribenzenesulfonate (PCMBS) was studied. ¶1 Mem- Iowa. brane ATPase of osmotically prepared platelet "ghosts" A foreleg of each of 20 dogs was perfused with blood is composed of Na+-K+-Mg++-dependent ATPase (15 to at a constant rate through the brachial artery. The 30%) and Mg++-activated ATPase (60 to 85%o). Ouabain nerves of the brachial plexus were transected, and an (10' M), which inhibits the Na+-K--dependent ATPase electrode was applied to their distal ends. Pressures were activity and produces a resultant loss of cellular K+, gain recorded simultaneously from the brachial artery and of Na+, and cell swelling, does not inhibit either ADP cephalic vein and from a small artery and small vein in aggregation or clot retraction. ¶f PCMB, an organic the paw. Pressor responses to injections of nor- mercurial compound that diffuses into cells, totally inacti- epinephrine (1, 2, and 4 /.tg) into the brachial artery and vates both ATPase activities in the ghost preparations to nerve stimulation (3, 6, and 12 cps) were measured and in the intact platelet. PCMBS, a highly polar, poorly before and after intra-arterial administration of 0.25 mg diffusible agent, also inhibits platelet membrane ATPase of phenoxybenzamine; measurements were repeated after activities as evidenced by a 35% cell swelling and the a second dose of 0.5 mg. Increases in total foreleg vascu- loss of up to 50% of the K+ content, but does not inhibit nor- clot retraction by the intact platelet. Both mercurials lar resistance that occurred in response to both 11 epinephrine and nerve stimulation were reduced moderately inhibited ADP aggregation. These observations indicate by phenoxybenzamine, but increases in venous resistance the existence of at least two distinct ATPase activities in were blocked completely. 11 Forearm blood flow (FBF) the human platelet. The Nae-Kt-dependent activity and forearm venous volume at a transmural pressure of necessary for maintaining cation content and cell volume 30 mm Hg (VVw0) were measured in 10 normal human resides within the platelet membrane, can be inactivated subjects with a mercury-in-rubber plethysmograph. Ob- by the PCMBS, but is not essential for clot retraction. servations on the responses of these parameters to infusions ATPase activity essential for clot retraction, by contrast, of norepinephrine (0.075 and 0.15 lug per minute) into the can be localized beneath the outer membrane of the intact brachial artery were made before and after intra-arterial platelet and is unaffected by ouabain or PCMBS. The injection of 0.5 mg of phentolamine; observations were demonstration that PCMBS inhibits ADP aggregation repeated after a second dose of 1.0 mg. Since blood but not clot retraction suggests that ADP aggregation pressure was unaltered, flow changes may be interpreted may not be a necessary step in the process of clot as changes in tone of resistance vessels. Changes in VVs0 retraction. represent changes in compliance of veins or capacitance vessels brought about by changes in tone of venous An Extrarenal Mechanism of Tolerance to Acute smooth muscle. Decreases in FBF with norepinephrine Potassium Loads. EDwARD ALEXANDER AND NORMAN were blocked only partially by phentolamine, whereas G. LEVINSKY,* Boston, Mass. decreases in VVw0 were blocked almost completely. 11 In Rats fed high potassium diets for several days usually these experiments the alpha adrenergic blocking agents survive acute potassium loads that are lethal to rats on phenoxybenzamine and phentolamine were more effective regular diets. It is generally assumed that this tolerance in blocking venous resistance and capacitance responses is due to enhanced urinary potassium excretion. To study to norepinephrine and nerve stimulation than they were tolerance, we fed 150-g rats regular rat diet (unadapted) in blocking prevenous responses to the same stimuli. or diet containing 10% KCl (adapted) for 5 days. Food was withheld for 24 hours before experiment. Without Human Platelet ATPase Activities: Relationship of an acute load, plasma K was equal: adapted, 4.2; un- Localization to Function. Louis M. ALEDORT, STAN- adapted, 4.4 mEq per L. Test rats were given KCl, 5 LEY B. TROUP, AND ROBERT I. WEED,* Rochester, N. Y. mEq per kg intraperitoneally; more than 90% of this was This investigation was undertaken to relate the absorbed within 2 hours. In unadapted rats, plasma K Na+-K+-activated ATPase activity of human platelets to was 5.8 + 1.4 mEq per L 1 hour later and 5.0 + 0.5 mEq the platelet ATPase activity known to be essential for per L 2 hours later. In adapted rats, plasma K was clot retraction. The specific consumption of ATP by significantly lower: 5.0 ± 0.9 at 1 hour (p < 0.05) and platelet ATPases was measured by the use of firefly 4.3 ± 0.5 at 2 hours (p <0.001). Urinary K excretion was less in adapted than in unadapted rats: adapted, * ASCI, active member. 274 + 138; unadapted, 404 + 131 at 2 hours (p <0.01). t ASCI, emeritus member. To confirm the nonrenal mechanism suggested by these ¶1 New paragraph. data, we performed studies on rats nephrectomized im- 980 AMERICAN SOCIETY FOR CLINICAL INVESTIGATION 981 mediately before KCl loading. Plasma K was again in Rh antibody/red cell systems was without prozone, lower in adapted rats 1 and 2 hours after loading: was specific for the Gm(a) factor even when tested with adapted, 4.4+± 0.7 and 5.4-+±0.8 mEq per L; unadapted, an anti-Rh coat of broad specificity for rheumatoid 5.6 + 0.8 and 7.4 + 2.1. The differences at both times factors, and was not inhibited by heat-aggregated Gm(a-) were highly significant (p < 0.01). The plasma bicarbon- 'yG-globulin. Chromatography on Sephadex at low pH ate decreased 3 mmoles per L 2 hours after loading in did not reveal hemagglutinating activity of other specifici- both groups. Isolated diaphragms from adapted and un- ties. Waaler-Rose activity was apparently independent adapted rats maintained identical K contents at equal of anti-Gm specificity by inhibition studies. Anti-Gm(a) external K concentrations in Ringer's medium, suggesting activity was removed by treatment with 0.1 M 2-mercap- that there is no intrinsic mechanism for adaptation. These toethanol and could not be inhibited by heat-aggregated experiments demonstrate a very potent nonrenal mecha- Gm (a-) -yG-globulin. This agglutinator was eluted in nism that regulates plasma K in adapted rats. Because late fractions from DEAE cellulose and was found to of rapid lowering of plasma K by this mechanism, renal sediment between the 19 S and 7 S regions in density excretion is actually decreased in adapted rats during the gradient ultracentrifugation. Gm (a) specific agglutinating first 2 hours after acute loading. activity was absorbed by a specific anti--yA-antiserum used in the region of antibody excess. Studies of this Effects of Left Ventricular Failure on the Pulmonary unique serum offer a further confirmation of the antibody Circulation. J. K. ALEXANDER,* H. L. FRED, M. A. concept of human anti-y-globulin activity by its demon- stration a MODELSKI, D. A. GONZALEZ, AND J. A. BURDINE, JR., in third immunoglobulin class (-yA). They Houston, Texas. provide a bridge between rheumatoid and nonrheumatoid anti--y-globulin antibodies and present an example of In 14 patients with clinical and hemodynamic findings defined isospecificity of hemagglutinating activity asso- of left ventricular failure, structural changes in the ciated with classical rheumatoid factors. pulmonary vasculature were identified by means of selec- tive angiography, and pulmonary capillary blood flow was assessed by Elevation Gradient of Lung Density. J. ALTOBELLI, R. lung scanning after injection of 'I macro- S. E. aggregated albumin. Thirteen patients with a high ACKERLEY, KETNER, M. A. TATTERSALL, AND J. L. calculated pulmonary vascular resistance and low cardiac PATTERSON, JR.,+ Richmond, Va. output demonstrated the following angiographic alterations In an earlier study, intrapleural pressure in the anesthe- at the lung bases bilaterally or unilaterally: 1) closer tized dog, held vertical, was found to increase 0.21 cm approximation of segmental vessels consistent with partial H20 for each cm of vertical distance. Mean lung density atelectasis, 2) narrowing and retarded filling of the in the end-tidal position was 0.22 g per ml lung. The segmental arteries and veins, and 3) abrupt attenuation of mechanism for the intrapleural pressure (Ppl) gradient segmental branch vessels. Pulmonary capillary blood is uncertain, but among the possibilities are 1) the lung flow, as indicated by the scanning technique, was rela- behaves as a homogenous fluid, or 2) a vertical gradient tively reduced in the lower lobes of these patients, whereas of lung density exists that affects the Ppl. The present normally flow to these regions is relatively increased. No investigation explored this second possibility. Ten anes- change in the hemodynamic or angiographic findings took thetized (pentobarbital) mongrel dogs were studied after place during inhalation of 100% 02 for 20 minutes. It has 45 minutes in the vertical head-up position, one in the been concluded that with a high level of pulmonary horizontal, and one in the vertical head-down position. vascular resistance and low cardiac output in left ven- Circulation was stopped by electrical fibrillation and the tricular failure, reduction in perfusion as well as in trachea clamped and thorax entered; pulmonary vessels vascular caliber of the lower lobes develops.

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