SUMMARY1. Methods are described for using the changes in respiration of intact Libinia nerve to follow the rate of energy utilization by the sodium pump in this tissue.2. Short tetani in 10 K(Na)ASW (artificial sea water in which Na is the major cation and the potassium concentration is 10 mM) increased the oxygen uptake which then declined exponentially. From the net influx of Na during the tetanus and the associated oxygen uptake, values between 19 and 3-4 were calculated for the Na: P ratio. After longer tetani, the recovery curve was S-shaped.3. The pump was activated by potassium ions in the external medium and this activation was competitively inhibited by external sodium ions.The data are consistent with a Michaelis constant (K.) for external potassium of 1 mm and an inhibitor constant (Ki) for external sodium of 60 mM.4. In activating the pump, K could be replaced by Tl+, Rb, NH4 and Cs ions; but, of the monovalent ions tested, sodium seemed to be unique in its inhibitory action.5. In sea waters containing 460 mM-Na, ouabain behaved like a mixed inhibitor of the pump, reducing both the maximum velocity and the apparent affinity for external potassium. At a given ouabain concentration, reducing the sodium content of the medium was without effect on the maximum rate of pumping; but the apparent affinity for potassium increased more steeply than in a ouabain-free solution.6. The rate of energy utilization associated with pumping was unaffected by inclusion of quite high concentrations of sulphydryl-blocking agents in the external medium.

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The relationship between muscle weakness and falls is probably modified by multiple characteristics of the individual, their culture, and their environment. Information from cross-cultural studies may provide new insights into effective fall prevention strategies for nursing home residents.

The expression of fibronectin in the repair process after myocardial infarction was studied using two protocols of coronary occlusion in the rabbit: a permanent occlusion or 3 h of occlusion followed by reperfusion (too late for salvage). We found a rapid and progressive increase in cardiac fibronectin expression in the infarcted region of the ventricle. Steady-state mRNA levels for fibronectin increased 13-and 16-fold, respectively, in the permanent and reperfused infarcts 1 d postinfarction. Immunological detection of the protein with a polyclonal antibody against plasma fibronectin showed significant increases of the protein fibronectin in the infarcted myocardium by day 3 in the reperfused group and by day 5 in the permanent coronary occlusion group. Ribonuclease protection assays established the induction of EIIIB containing fibronectin mRNA in both models by day 1 and use of a monoclonal antibody showed an increase in the EIIIA isoform 2 d postinfarction. Increases in steadystate mRNA levels for several collagen types were found in both groups, but these changes occurred after those noted for fibronectin. Thus fibronectin mRNA and protein expression increased rapidly postinfarction suggesting a functional role in the repair process. (J. Clin.

Adequacy of healing after acute myocardial infarction may determine the incidence of postmyocardial infarction rupture and ventricular aneurysm. Accordingly, in 36 rabbits, from 1 to 8 days after coronary ligation, and in 18 shams, we measured collagen formation and mechanical resistance of the infarcted left ventricle to stretch and rupture. Prolyl hydroxylase, an intracellular enzyme of collagen synthesis, increased from control activity of 3970 ± 431 to 9224 ± 643 counts/min per mg (cpm/mg) extractable protein (P < 0.01) at 48 hours and was nearly maximal at 3 days postmyocardial infarction (14,518 ± 2,030 cpm/mg, P < 0.01). Lysyl oxidase, an extracellular collagen cross-linkage enzyme, increased from control activity of 29.6 ± 4.8 to 74.7 ± 18.8 cpm/mg extractable protein (P < 0.01) at 72 hours and peaked at 121.5 ± 7.3 (P < 0.01) 4-6 days postmyocardial infarction. Hydroxyproline, a measure of collagen content, increased from control of 2.8 ± 0.2 to 5.3 ± 0.6 mg/g dry weight (P < 0.05) at 72 hours and continued to increase at 8 days postmyocardial infarction (14.5 ±1.7 mg/g dry weight; P < 0.01). When enzyme activities and hydroxyproline content were expressed relative to other reference bases, including DNA, tissue protein, dry weight, and total left ventricle, similar results were obtained. The mechanical properties of the infarcted left ventricle were determined by filling a balloon in the excised left ventricle until rupture. The rupture threshold in the normal left ventricle, [664 ± 43 mm Hg (n = 16)], was not significantly different from that of the infarcted left ventricle on days 1-8 postmyocardial infarction. However, left ventricular rupture occurred more often through the myocardial infarction on days 1-4 postmyocardial infarction (59%) than on days 6 and 8 (18%; P = 0.03) when collagen content had significantly increased. Wall stress at the point of rupture in left ventricles from shams and normals was 30 ± 2 g/mm 2 ; tensile strength in isolated left ventricle muscle strips was 25 ± 4 g/mm 2 and in isolated scar strips at 7 days postmyocardial infarction was 59 ± 7 g/mm 2. The passive stiffness of the infarcted left ventricle increased from control of 61 ± 5 to 94 ± 6 mm Hg/100 fi\ (P < 0.05) at 4 days and 100 ± 7 mm Hg/100 pi (P < 0.01) at 6 days postmyocardial infarction. Stiffness correlated with hydroxyproline content over the 8 days postmyocardial infarction (r = 0.599; P < 0.001). Thus, the acutely infarcted ventricle was highly resistant to rupture during the initial 48 hours postmyocardial infarction, before any increase in collagen occurred. This result suggests that the preinfarction collagen content has an important role in preventing rupture. After 72 hours postmyocardial infarction, collagen synthesis appeared to be a determinant of infarct stiffness and resistance of the infarcted ventricle to rupture. (Circ Res 53: 378-388, 1983)

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Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end‐stage renal disease. One of the cornerstones of treatment is the use of phosphate‐binding agents. We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder. This trial is a three‐period, international, multicenter, randomized, controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder, consisting of a 2‐week washout period, a 52‐week safety assessment period in which subjects are randomized to ferric citrate or active control, and a 4‐week efficacy assessment period in which subjects randomized to ferric citrate in the safety assessment period are randomized to ferric citrate or placebo. Eligible subjects include end‐stage renal disease patients who have been treated with thrice‐weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel. Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus. Safety assessments will be performed by monitoring adverse events, concomitant medication use, and sequential blood chemistries (including iron parameters, phosphorus, and calcium). This three‐period trial will assess the efficacy of ferric citrate as a phosphate binder. If proven safe and efficacious, ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders.