Favorable effects of oral maintenance digoxin therapy on left ventricular performance in normal subjects: echocardiographic study

Left ventricular performance was assessed with echocardiography in 10 normal subjects before and during maintenance therapy with digoxin (0.5 mg/day orally) in the basal state and after acute pressure loading with intravenously administered phenylephrine. During digoxin therapy, despite a decrease in mean heart rate of 5 beats/min in the basal state, mean left ventricular ejection fraction increased from 74 +/- 2 to 79 +/- 1 percent (standard error, P less than 0.03); percent shortening of a left ventricular minor dimension increased from 37 +/- 2 to 41 +/- 1 percent (P less than 0.04) and the mean rate of left ventricular dimension shortening increased from 5.66 +/- 0.22 to 6.31 +/- 0.23 cm/sec (P = 0.05). During acute pressure loading with phenylephrine there was no change in mean heart rate after digoxin and mean ejection fraction increased from 69 +/- 3 to 75 +/- 2 percent; mean percent shortening increased from 33 +/- 2 to 38 +/- 2 percent; mean rate of shortening increased from 5.46 +/- 0.32 to 6.48 +/- 0.33 cm/sec and mean normalized rate of shortening increased from 1.11 +/- 0.06 to 1.29 +/- 0.05 sec-1 (all P less than 0.01). In a few subjects the response to digoxin did not coincide with the mean data for the whole group. This variability was largely due to difficulties in exactly matching heart rate between the control and digoxin studies. These data (1) support the concept that long-term oral digoxin therapy exerts a positive inotropic effect on the normal left ventricle, and (2) demonstrate the usefulness of echocardiography in nonivasive assessment of the effects of drugs on left ventricular performance.     

Prevalence of gram-negative rods in the normal pharyngeal flora

We obtained throat cultures from 100 randomly selected people free from any chronic upper or lower respiratory disease who did not work in a hospital and who had not experienced any acute illness or received any antibacterial therapy in the 4 weeks preceding culture. Eighteen percent harbored either a species of Enterobacteriaceae or Pseudomonas aeruginosa in their pharynx. In all cases, colony counts were low, the majority being detected in broth media selective for Gram-negative rods. There were no clear-cut age or sex distributions of Gram-negative pharyngeal carriage. These data imply that, in at least some cases, isolation of Gram-negative rods from sputum of untreated patients may be a normal finding, and that in some patients with pulmonary infection, the pretreatment, upper respiratory tract flora may serve as the source of subsequent superinfection with Gram-negative rods.     

Effects of calcium antagonist, 6-(N, N-diethylamino) hexyl-3, 4, 5-trimethoxybenzoate, on digitalis-induced arrhythmias and cardiac contractions

6-(N, N-Diethylamino) hexyl-3, 4, 5-trimethylbenzoate (TMB-6) and lidocaine were equipotent (1 mg/kg) in the conversion of ectopic rhythms to normal rhythms in digoxin-toxic dogs. However, TMB-6 had fewer side effects on heart rates and dp/dt than lidocaine. TMB-6 inhibited the contractile force of electrically stimulated dog and guinea-pig atria and ventricles at concentrations ranging from 2.5 X 10(-5) to 1.7 X 10(-4) M. Elevation of extracellular Ca++ concentrations from 2.7 to 5.4 mM produced a significant increase in the ID50 of TMB-6 in atria (from 2.5 X 10(-5) to 5.0 X 10(-5) M in dogs and from 7.2 X 10(-5) to 1.0 X 10(-4) M in guinea pigs). TMB-6 (7.3 X 10(-5) to 2.4 X 10(-4) M) depressed the amplitude of Ca++-dependent action potentials in depolarized dog cardiac Purkinje fibers. These results are discussed with regard to the antagonism of TMB-6 on Ca++ availability in the myocardium which leads to the conversion of cardiac arrhythmias.     

Protein hydration in solution: experimental observation by x-ray and neutron scattering

The structure of the protein-solvent interface is the subject of controversy in theoretical studies and requires direct experimental characterization. Three proteins with known atomic resolution crystal structure (lysozyme, Escherichia coli thioredoxin reductase, and protein R1 of E. coli ribonucleotide reductase) were investigated in parallel by x-ray and neutron scattering in H2O and D2O solutions. The analysis of the protein-solvent interface is based on the significantly different contrasts for the protein and for the hydration shell. The results point to the existence of a first hydration shell with an average density approximately 10% larger than that of the bulk solvent in the conditions studied. Comparisons with the results of other studies suggest that this may be a general property of aqueous interfaces.