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Biomedical subjects

A H Goldberg

Publications and source records attributed to A H Goldberg.

At least 19 recordsLinked to original sources

Canine end-systolic pressure-length relationships: depressed by diltiazem, invalidated by ischemia.

This study was designed to determine whether the end-systolic pressure-length relationship (ESPLR) reflects changes in regional contractility during the imposition of graded ischemia, and whether it is modified by diltiazem during propofol anesthesia. Seven beagles were anesthetized and instrumented to measure left ventricular pressure and subendocardial segment lengths (sonomicrometry) in the region of the left anterior descending (LAD) and circumflex (LC) arteries. Afterload was increased by the tightening of a snare around the descending thoracic aorta. Pressure-length loops were constructed and the slope of the ESPLR and the x-axis intercept, Lo, were calculated. Graded ischemia of the apical myocardium only was accomplished by the tightening of a micrometer-controlled snare around the LAD to produce Critical Constriction (CC), Ischemia 1 and 2 (I1, I2), and Total Occlusion (TO). In the basal LC region, LAD ischemia had no effect on either the ESPLR slope or Lo. In contrast, the ESPLR slope in the LAD area was decreased by ischemia at I1 (-40%), increased at TO (+69%), and unchanged at CC and I2, and was reduced by diltiazem at CC and I2 (-31% and -36%, respectively). The LAD ESPLR Lo was increased by ischemia by 64% and 61% at I2, and 91% and 122% at TO, before and after diltiazem, respectively. In the LC region, diltiazem decreased systolic shortening and the ESPLR slope. These results indicate that diltiazem has negative inotropic properties in both ischemic and nonischemic areas. Also, Lo is not a constant and must always be redetermined for every intervention. In the absence of ischemia, the ESPLR may be a reliable measure of myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Viscoelastic properties of polyacrylic acid gels in mixed solvents.

The objective of this study is to investigate the viscoelastic properties of Carbopol 934P polymeric systems in a variety of mixtures of pharmaceutical solvents. Carbopol 934P neutralized with a 1:1 equivalent ratio of triethanolamine was dissolved in various binary or ternary solvent mixtures consisting of propylene glycol, glycerol formal, and water. Dynamic moduli G' and G'', complex viscosities, eta' and eta'', and loss tangent, tan delta, were examined over a frequency range of 10(-3) to 10 Hz using an oscillatory viscoelastic rheometer at 30 degrees C. The results indicated that for 0.5-1.5 wt% neutralized Carbopol in ternary mixtures, G' and G'' increased by 3-4 orders of magnitude and the phase angle decreased from 80 to 25 degrees when the water content in the solvent mixture increased from 10 to 80 wt%. These studies also indicated that the addition of water to nonaqueous Carbopol 934P polymer systems transforms them from low-viscosity solutions to gels with significant elastic behavior involving physical interaction and entanglement of polymer segments with solvents.

Acrylic Resins

Viscometric study of polyacrylic acid systems as mucoadhesive sustained-release gels.

This report describes a novel nonaqueous polymeric formulation that exhibits low-viscosity fluid behavior for ease of spraying with conventional nebulizer, which when sprayed into the nasal cavity, transforms to a high-viscosity gel for efficient retention and drug absorption. The transformation occurs because of the rheological changes induced by a change in the solvent composition of the polymeric formulation in the moist nasal cavity. Such a rheological change would then facilitate enhanced residence time of the drug at the site of administration in order to avoid drainage losses. This study reports the results of the effects of a variety of factors such as solvent composition and polymer concentration on the rheological properties of a polyacrylic acid polymer. An attempt to correlate viscosity enhancement effects with enhanced and sustained-release behavior of propranolol, a drug that undergoes extensive first-pass effects, from such formulations via nasal administration in beagle dogs is also described.

Acrylic Resins

Mixture experimental design in the development of a mucoadhesive gel formulation.

The objective of the present study is to apply response surface methodology to the design and analysis of composite experiments containing independent covariate(s). The approach is illustrated here by the study of viscosity characteristics of a polymeric mucoadhesive formulation in multicomponent solvent vehicles. The nonaqueous formulation will produce a gel network with significant rheological change when in contact with body fluids. The process of water inclusion will induce not only solvent compositional change of the mixture but also concomitant dilution of the polymer concentration. To study the viscosity change over the solvent compositions and polymeric concentrations of interest, an experimental design is utilized consisting of a 10-point simplex-centroid lattice augmented with three interior points at each polymeric concentration. The contour patterns are compared with the experimental data using the variance and lack of fit, starting with the Scheffe linear model and building up to the full cubic model including the covariate terms. The fitted model provides information needed to predict optimum formulations, i.e., initial viscosity of less than 100 cP, but yielding rheological profiles commensurate with high degrees of substantivity when diluted with water. For illustrative purposes, the Carbopol resins neutralized with a 1:1 molar equivalent ratio of triethanolamine in three primary solvents, propylene glycol, glycerol formal, and water, were chosen for this study.

Acrylic Resins

Chromatin-associated glycoproteins of normal rat liver and Novikoff hepatoma ascites cells.

Glycoproteins were demonstrated in the 0.6 M NaCl extract of chromatin of normal liver and Novikoff hepatoma cells by periodic acid-Schiff staining of sodium dodecyl sulfate-polyacrylamide gels. In chromatin extracts of Novikoff hepatoma cells, six major periodic acid-Schiff-positive bands coincident with Coomassie Blue-stained protein bands were found with molecular weights of 30,000, 54,000, 64,000, 75,000, 104,000, and 127,000. A corresponding extract from normal rat liver chromatin revealed the presence of four major periodic acid-Schiff-positive bands that migrated with protein bands at molecular weights of 16,000, 30,000, 54,000, and 75,000. The glycoproteins of these extracts contained either mannose or alpha-D-glucose, fucose, and N-acetylglucosamine as shown by the specificity of lectins in affinoelectrophoresis. One of the glycoproteins detected by affinoelectrophoresis was very basic.

Animals

Isolation and characterization of nonhistone chromosomal protein C-14 which stimulates RNA synthesis.

The nonhistone chromatin protein, C-14, was extracted from chromatin of Novikoff hepatoma ascites cells and isolated in high purity as shown by its migration as a single dense spot on two-dimensional polyacrylamide gels. Its mobility on sodium dodecyl sulfate gels is consistent with a molecular weight of approximately 70 000. The amino acid composition shows that protein C-14 has an acidic:basic amino acid ratio of 1.8. Its amino terminal amino acid is lysine. Protein C-14 stimulated the incorporation of [3H]UMP into RNA by approximately 30% when added to naked DNA and homologous RNA polymerase I. A 30% stimulation of [3H]UMP incorporation into RNA was also found when protein C-14 was added to an E. coli RNA polymerase system containing either E. coli or Novikoff hepatoma DNA.

Amino Acid Sequence

The effects of halothane on pregnant and nonpregnant human myometrium.

Strips of myometrium were obtained at operation from eight nonpregnant and ten pregnant patients. The tissues were immediately suspended in a muscle bath and induced to contract isometrically with K2SO4 in the presence and absence of halothane (0.5 to 2.0 vol per cent). The anesthetic produced significant dose-related depression of developed tension and rates of increase and decrease of tension in both pregnant and nonpregnant muscles. Time to peak tension was increased in the nonpregnant but not in the pregnant muscles. The depressant effect of the lower halothane concentrations (less than 1.1 vol per cent) was significantly greater in the pregnant muscles.

Adolescent

Halothane and calcium interaction in isolated pregnant and postpartum rat myometrium.

Isolated strips of mid-pregnant and postpartum rat myometrium were rendered functionally Ca2+-free by exposure to a Ca2+-free modified Krebs-bicarbonate solution containing 1 mM EGTA. The muscle strips were then exposed to 2.25 mM Ca2+ for periods of 15 to 600 seconds for the mid-pregnant tissues and one 120-second period for the postpartum tissues. At the end of each exposure, Ca2+ was removed and simultaneously each muscle was depolarized with 125 mM K2SO4. Isometric tension changes in the muscles were measured with and without 0.5 per cent halothane. In the mid-pregnant muscles, halothane diminished the initial tension development in response to Ca2+ by approximately 50 per cent, regardless of the duration of Ca2+ exposure. The contractile response of these muscles to depolarization with K2SO4 was reduced 10 per cent by 0.5 per cent halothane; this was probably due to reduction in transmembrane influx of Ca2+. In the postpartum muscles, the initial tension development in response to Ca2+ was threefold greater than in mid-pregnant muscles and was reduced 25 per cent by halothane. These tissues failed to develop by any tension in response to K2SO4. The most likely explanation for the effect of halothane is that it reduces the transmembrane influx of Ca2+ in both types of tissues, but that the postpartum sarcoplasmic reticulum present less competition for intracellular Ca2+ than pregnant sarcoplasmic reticulum.

Animals

Heart muscle performance after experimental viral myocarditis.

As part of an inquiry into possible antecedents of idiopathic cardiomyopathy, acute experimental coxsackie virus myocarditis was studied for late structural and functional sequelae. Myocarditis was induced in 12- and 22-day-old hamsters by inoculation with coxsackie virus B3. Early viremia occurred, followed by virus replication in heart muscle. Maximum peak developed tension (Tpd) of isometrically contracting isolated heart muscle was depressed 17 and 43% in the animals inoculated at 12 days, and studied 18 and 90 days later, respectively, as compared to their uninoculated controls. In both infected groups, less muscle stretch was required to reach the length at which Tpd was produced. Animals studied 180 days after inoculation did not differ from controls. The muscles from animals inoculated at 22 days of age and studied 18 days later showed a 15% depression of Tpd compared to their controls. Glycerinated muscles from this infected group developed 50% less tension than their controls. The muscles of hamsters inoculated with virus at 22 days and studied 90 and 180 days later showed no change in Tpd. The data suggest that contractility and compliance of heart muscle are decreased 18 days after inoculation, but recover by 90 days if the animals are inoculated at age 22 days. However, if the animals are inoculated at a younger age (12 days), depression of myocardial performance persists for at least an additional 90 days. It is concluded that the inflammatory stage of experimental acute coxsackie virus B3 myocarditis in the Syrian golden hamster may be followed by residual alterations in contractile proteins and myocardial function.

Animals

Halothane and isometric contractions of isolated pregnant rat myometrium.

The effects of halothane on isometirc contractions of isolated pregnant uterine muscle strips were evaluated in tissue obtained from 13 midpregnant rats. Peak developed tension was depressed in a dose-related manner at halothane concentrations above 0.8 vol per cent, but was not affected at lower halothane concentrations. Time to peak tension was reduced 10-20 per cent, and relaxation time, 10 per cent, by halothane concentrations ranging up to 2.2 per cent. Total resting tension consisted of a passive component and a calcium-dependent component. In concentrations above 0.8 per cent, halothane rapidly removed 100 per cent of the calcium-dependent resting tension. At lower concentrations, halothane reduced it 50 per cent. The passive component of resting tension was unaffected by halothane. These actions of halothane can prevent postpartum hemostasis. They occur even with very low anesthetic concentrations and can be detected soon after introduction of anesthetic into the muscle bath. This indicates that the hemostatic hazards associated with the use of halothane for delivery may not be prevented by limiting the concentration of halothane or the duration of anesthetic exposure.

Anesthesia, Obstetrical

Fluroxene and isolated heart muscle.

The direct myocardial effects of fluroxene were examined in isometrically and isotonically contracting isolated rat heart muscle. MAC, the minimum anesthetic concentration needed to prevent movement in response to tail clamping, was found to be 5.0 vol per cent fluroxene in the rat. At 4.6 vol per cent fluroxene, peak developed isometric tension and maximum rate of tension development were decreased 29 and 24 per cent, respectively. At 11 vol per cent, the depressions were 39 and 33 per cent. At 26.4 vol per cent, the depressions were around 60 per cent. Vmax (the maximum shortening velocity of unloaded muscle) of the force-velocity relation was unaltered by fluroxene concentrations of 0.8, 4.6, and 11 vol per cent. Even at 26.4 vol per cent, the depression in Vmax was only 25 per cent. Po (the maximum force at zero velocity), work, and power were lowered much more, with reductions ranging from 15 to 27 per cent at 4.6 vol per cent, from 40 to 42 per cent at 11.0 vol per cent, and from 65 to 69 per cent at the 26.4 vol per cent. Series elastic extension was unchanged at 0.8 and 4.6 vol per cent fluroxene, but was decreased 16 per cent at 11.0 vol per cent and 46 per cent at 26.4 vol per cent fluroxene. The data indicate the fluroxene has a direct negative inotropic effect that is associated with increased series elastic stiffness, but does not involve Vmax of the force-velocity relation until quite high anesthestic concentrations are reached. Comparative studies were also carried out with halothane. MAC for halothane in the rat was 1.0 vol per cent. The relative potency of halothane compared with fluroxene in depression of Vmax was 13.2, and its relative potency in depression of Po, 4.0.

Anesthesia, Inhalation

Depressed myocardial function in subacute experimental viral myocarditis.

A model of experimental Coxsackie virus B3 myocarditis has been developed in the weaning Syrian golden hamster. The acute infection is characterized by extensive viral replication in the myocardium, associated with transient myocytolysis and leukocytic infiltration. At 2 weeks after inoculation, there is survival without evidence of cardiac hypertrophy or failure, and minimal residual light microscopic changes. In order to evaluate myocardial function during convalescence form this form of myocarditis, muscle mechanics were studied in left ventricular trabeculae careae in 10 infected and 7 control animals, 18 days after inoculation. Maximum developed tension of the infected animals was depressed by 25%, and there was a significant decrease in the time to peak tension. Furthermore, the infected muscles required less stretch to reach that length at which maximal developed tension was produced. These data indicate that myocardial function remains depressed during early convalescence from acute Coxsackie virus B3 myocarditis and suggest that this state is associated with decreased compliance. Studies of myocardial morphology and function at longer intervals after acute experimental viral myocarditis are indicated, to further test the hypothesis that viral myocarditis might be a precursor chronic isiopathic cardiomyopathy.

Animals