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Biomedical subjects

C R Bridges

Publications and source records attributed to C R Bridges.

At least 37 records · Page 2Linked to original sources

Skeletal muscle ventricles for total heart replacement.

Skeletal muscle ventricles (SMV) were constructed from canine left latissimus dorsi muscle. The animals were divided into three groups: group A (n = 5), SMVs rested 4 weeks without electrical conditioning; group B (n = 6), SMVs rested 4 weeks and then electrically conditioned for 6 weeks; group C (n = 5), SMVs rested 18 weeks without electrical conditioning. At the end of each protocol, the SMVs were acutely tested by connecting them to a mock-circulation device. The SMVs in group C developed stroke work at physiologic preloads superior to any previously reported, as high as 194% of left ventricular stroke work at afterloads of 80 mmHg. The SMVs in group B developed work outputs equivalent to 53% of the left ventricle, which is still more than four times that of the right ventricle. The results show that it is possible to harvest sufficient work from skeletal muscle ventricles to fully replace cardiac function at physiologic preloads.

Adaptation, Physiological↗

Skeletal muscle ventricles: improved performance at physiologic preloads.

We attempted to construct skeletal muscle ventricles (SMVs) so that they would develop optimal stroke work at physiologic preloads of 5 to 15 mm Hg. Thirty-one SMVs were constructed in mongrel dogs. The effects of electrical preconditioning with 2 Hz continuous and 25 Hz burst patterns were evaluated, as well as the application of passive stretch to the muscle fibers during preconditioning. We evaluated the stroke work developed by these SMVs at afterloads of 30 mm Hg and 80 mm Hg in vivo, using a mock circulation device. During mock circulation studies, the SMVs were stimulated via the thoracodorsal nerve with either a 25 Hz or 85 Hz burst pattern. SMVs with 2 Hz preconditioning developed significantly higher stroke work than SMVs with 25 Hz preconditioning under all conditions of afterload, preload, and stimulation frequency (p less than or equal to 0.001). Under these conditions, for the 2 Hz preconditioned SMVs, passive stretch during preconditioning resulted in a further significant increase in developed stroke work (p less than 0.05). For these SMVs, with an 85 Hz stimulation frequency, stroke work averaged 410% of canine RV stroke work, and 59% of canine LV stroke work at physiologic preloads and afterloads.

Animals↗

Antirheumatic agents: CNS toxicity and its avoidance.

Altered drug metabolism, polypharmacy, multiple diseases, and errors in self-medication are all factors seen in the elderly which increase the risk for side effects from antirheumatic drug therapy. The geriatric presentation of central nervous system (CNS) toxicity, which is common yet frequently overlooked, is reviewed as it pertains to various drugs commonly used to treat rheumatic disease. Practical advice on avoiding common pitfalls in antirheumatic prescribing is offered.

Aged↗

Functional right-heart replacement with skeletal muscle ventricles.

Skeletal muscle ventricles were constructed from the latissimus dorsi in seven dogs. All skeletal muscle ventricles underwent a vascular delay period followed by 4-7 weeks of electrical preconditioning. In group 1 (n = 5), the skeletal muscle ventricle was used to replace native right-heart function. Venous return from the superior and inferior venae cavae was directed to the skeletal muscle ventricle with outflow directed to the pulmonary artery. In group 2 (n = 2), the skeletal muscle ventricle was used for partial bypass of the right heart. In both groups, right-heart bypass was continued for as long as 8 hours. In group 1 after 4 hours of continuous complete right-heart bypass, stroke work was 163 +/- 63% of canine right ventricular stroke work. Skeletal muscle ventricle output was 1.14 +/- 0.02 l/min, central venous pressure was 13 +/- 1.5 mm Hg, and systemic systolic blood pressure was 95 +/- 9 mm Hg. Skeletal muscle ventricles are capable of performing the work of the right heart with near-physiological filling pressures.

Animals↗

Acute, fatal illness in cattle exposed to boron fertilizer.

Twenty-six cows died after accidental exposure to boron fertilizer. Cows developed diarrhea, weakness, ataxia, signs of depression, and died, usually within a few hours. Seizure-like behavior was noticed in 2 cows, and 2 were suspected of aborting. High boron concentrations in tissues from affected cows confirmed ingestion of an appreciable amount of boron fertilizer. In an attempt to confirm the diagnosis of boron poisoning, boron fertilizer was administered to goats. A kid goat given 3.6 g of fertilizer/kg of body weight developed clinical signs similar to those seen in the cattle. Boron compounds such as sodium borate and boric acid have been considered generally nontoxic, and reports of livestock toxicosis are uncommon. This case report suggests that these compounds may be palatable under certain circumstances leading to ingestion of toxic quantities.

Animals↗

Physiological adaptations of the intertidal rockpool teleost Blennius pholis L., to aerial exposure.

Gas exchange, metabolism, ventilation, circulation and acid-base balance in water and air were investigated in Blennius pholis. The rates of gas exchange in water and air were similar with the RQ remaining around 0.8. Aerial gas exchange was equally divided between the head/gills and the tail region. Ventilatory adaptations involved a reduction in rate in air and the mode of ventilation changed from flow-through to tidal, with closed opercula. A transient bradycardia developed on transition to air before heart frequency (fH) returned to aquatic levels. During aerial exposure PvCO2 rose only by 1 Torr with a concomitant decrease in pH of 0.19 pH-units. At the same time a metabolic acidosis was observed which could not be fully accounted for by the formation of lactic acid in the blood, although tissue lactate levels did not change significantly. No histological evidence was found for the presence of carbonic anhydrase in the epithelial cells of the skin or the oesophagus to aid aerial CO2 excretion. Inhibition of CA activity by addition of methazolamide to blood, however, caused PvCO2 to rise by 3 Torr and pHv to decrease by 0.4 pH unit. It is concluded that B. pholis is physiologically well adapted to aerial exposure through adjustments in ventilation and circulation and that erythrocytic carbonic anhydrase plays a major role in CO2 transfer.

Acid-Base Equilibrium↗

Long-term neurostimulation of skeletal muscle: its potential for a tether-free biologic cardiac assist device.

Skeletal muscle has a tremendous capacity to adapt. This adaptive phenomenon is seen perhaps to the greatest extent when skeletal muscle is subjected to chronic low frequency stimulation via the motor nerve. There is a decrease in glycolytic enzymes and an increase in oxidative enzymes, as well as a change in the contractile proteins and an increase in the mitochondrial volume fraction of the muscle fiber. These adaptive changes result in a muscle that is considerably more fatigue-resistant. Specifically herein, we report on a pneumatic aortic counterpulsator device powered by skeletal muscle. These muscle pumps functioned continuously and pumped blood effectively in tether-free animals for several weeks.

Adaptation, Physiological↗

Oxygen binding in blood of Xenopus laevis (Amphibia) and evidence against Root effect.

Blood oxygen binding was examined in the amphibian, Xenopus laevis, with the particular aim of determining whether the O2 capacity is diminished when blood pH is lowered, which is known as the Root effect in blood of some fishes. Hemoglobin-bound O2 concentration, [O2Hb], was determined by the Lex-O2-Con technique, and both total hemoglobin, [Hb]tot, and Met-hemoglobin, [MetHb], contents were measured spectrophotometrically. From these measurements were calculated the oxygen capacity, O2cap, and the content of active hemoglobin, [Hb]act, i.e. the difference between [Hb]tot and [MetHb]. The main finding was the independence of the ratio of O2cap/[Hb]act on pH, when differences between samples in [Hb]tot and the presence of MetHb, which was particularly pronounced at low pH, where properly accounted for. It is concluded that the Root effect does not exist in blood of the amphibian Xenopus laevis.

Animals↗

Heteroporous model of glomerular size selectivity: application to normal and nephrotic humans.

A heteroporous model of the glomerular filtration barrier was developed and used to interpret dextransieving data in healthy volunteers (normal controls), in patients with nephrotic range proteinuria (grouped as grades I-III, according to severity), and in a group of previously nephrotic patients whose proteinuria was in remission ("resolved controls"). Several hypothetical pore-size distributions were compared in terms of their ability to describe the selective increases in the fractional clearance of large dextrans observed with increasing severity of proteinuria. The most successful model examined was based on the assumption that the major portion of the capillary wall functions as an isoporous membrane, but that a small fraction of the filtrate passes through pores that are unable to discriminate among dextrans of different sizes. The value of the membrane parameter that reflects the relative importance of the nonselective pores was found to increase in parallel with the fractional clearance of immunoglobulin G; it increased progressively in going from normal controls to resolved controls to grades I-III nephrotics. The observed patterns of protein excretion could not, however, be explained entirely by a loss of glomerular size selectivity. Variations in membrane selectivity on the basis of molecular charge and/or molecular configuration are also likely to have been important.

Glomerular Filtration Rate↗

Modulation of haemocyanin oxygen affinity in the intertidal prawn Palaemon elegans (Rathke).

The modulation of haemocyanin oxygen affinity was studied at 10 degrees C in the blood of the intertidal prawn Palaemon elegans. On increasing the L-lactate concentration in dialysed blood from 0 to 9.1 mM, P50 decreased from 27 to 11 torr at pH 7.8. Undialysed blood exhibited a higher oxygen affinity than dialysed blood with the same lactate concentration indicating the presence of an unidentified factor which increased oxygen affinity. After dialysis both winter and summer blood exhibited the same intrinsic oxygen affinity and response to lactate. The response of oxygen affinity to lactate was exponential, low concentrations of lactate (0-5 mM) markedly increasing oxygen affinity. The lactate effect in dialysed blood expressed as delta logP50/delta log[L-lactate] was -0.56 at pH 7.8 and -0.63 at pH 7.4. The effect of lactate on oxygen affinity, delta P50, was similar in dialysed and whole blood. The effect of the unidentified factor (delta P50, between dialysed and undialysed blood) at the same lactate concentration was 13.1 and 15.1 torr at pH 7.8 in winter and summer blood, respectively. At pH 7.4 the delta P50 was 38 torr for both summer and winter blood. Differences in oxygen affinity between blood collected in summer and winter could be explained by differences in blood lactate concentrations.

Animals↗

Biophysical basis of glomerular permselectivity.

The mammalian glomerular capillary wall normally restricts the transmural passage of plasma proteins while offering little resistance to the filtration of water and small solutes. The basis for this selectivity has been explored extensively in recent years, through clearance measurements of endogenous (mainly albumin, transferrin, and immunoglobulins) and exogenous (horseradish peroxidase) proteins, and a variety of nonprotein polymers such as dextrans and polyvinylpyrrolidone. In conjunction with efforts to localize particulate and soluble tracers by high resolution ultrastructural techniques, such measurements have now made it possible to define the determinants of the glomerular filtration of macromolecules in terms of discrete structural barriers as well as such biophysical influences as hemodynamics and the molecular size- and charge-selective characteristics of the capillary wall. These experimental approaches have been aided greatly by the development of theoretical models that enable investigators to describe macromolecular filtration in terms of hydrodynamic principles applied to isoporous membranes. Although the initial models failed to consider the important role of membrane fixed negative-charge characteristics in influencing protein filtration, this shortcoming has led to the recent introduction of a theoretical model that also takes this factor into consideration. The aim of this brief review is to summarize these various theoretical approaches to the understanding of glomerular permselectivity and, wherever possible, to cite specific tests of these theories based on experimental studies in humans and animals.

Animals↗

Root effect induced by CO2 and by fixed acid in the blood of the eel, Anguilla anguilla.

The decrease in O2 capacity with decreasing pH (Root effect) was studied in eel blood in which pH was varied in the range 5 to 9 both by addition of acid or base (fixed-acid Root effect) and by varying PCO2 (CO2 Root effect). Hemoglobin-bound oxygen was independent of PO2 above 150 Torr and was thus referred to as O2 capacity (O2cap). At pH below 8.5, O2cap decreased sigmoidally with pH to attain, below a pH of 6.0, a value which, at 15 degrees C, averaged about 48% of the maximum O2cap, measured above pH 8.5. At 25 degrees C, this reduction was even more pronounced. For pH above about 6.5 the decline in O2cap was independent of whether the pH was diminished by CO2 or by fixed acid. Below pH 6.5, however, the CO2 Root effect exceeded the fixed-acid Root effect. Below pH of 7.5, the buffer value of true plasma increased with declining pH and attained a negative value in the range where CO2 exerted a specific action on the Root effect.

Acids↗

Buffering and CO2 dissociation of body fluids in the pupa of the silkworm moth, Hyalophora cecropia.

To assess the extent of CO2 storage and the changes in the acid-base status that occur during intermittent CO2 excretion in insects, total CO2 content and pH were measured in whole body homogenates (= tissue homogenates) of Hyalophora cecropia pupae at various levels of Pco2 at 20 degrees C. The CO2 dissociation curve, i.e. plot of total CO2 content in tissue homogenates against Pco2 was nearly linear in the Pco2 range from 15 to 50 Torr, the mean slope being 0.138 mM . Torr-1. This value, which constitutes the effective CO2 solubility, was nearly three times the physical solubility in the tissue homogenate which averaged 0.053 mM . Torr-1. Plots of bicarbonate concentration in whole body tissue water against pH yielded an average buffer value of 75 mmol . pH-1 per kg tissue water. The high buffer value results in a small pH change, about 0.04 units, when Pco2 varies between 20 and 45 Torr in the respiratory cycle. The absolute value of mean tissue pH at Pco2 = 30 Torr predicted from the buffer line, 6.57, agrees well with direct measurement in hemolymph samples.

Animals↗

Glomerular charge alterations in human minimal change nephropathy.

A theoretical model of charge and size selectivity for the glomerulus has been applied to human data. Using previously published values for GFR, renal plasma flow, systemic oncotic pressure, and fractional clearances of neutral dextrans, albumin, salivary amylase, and transferrin, membrane parameters describing the glomerular barrier were determined for normal individuals under control conditions and during lysine infusion (which retards tubule protein reabsorption), and for patients with minimal change nephropathy (MCN). To permit the estimation of membrane charge from fractional clearances, molecular charge values for human transferrin (-9.4 Eq/mole) and human salivary amylase (-4.1) were determined by measuring electrophoretic mobilities of these proteins in polyacrylamide gels. Assuming no large changes in the transmural hydraulic pressure difference (delta P), the glomerular ultrafiltration coefficient (Kf, the product of hydraulic permeability and capillary surface area) was calculated to be reduced by greater than 50% in MCN. The effective pore radius (approximately 55 A) is virtually unaltered in MCN, suggesting that the decline in Kf is due to a reduced number of pores. The degree of albuminuria observed in MCN is attributable to an approximately 50% reduction in the concentration of fixed negative charges in the glomerular capillary wall. The concentrations of fixed charges calculated from albumin data in normal individuals (140 to 160 mEq/liter) and in patients with MCN (60 to 90 mEq/liter) are insensitive to the assumed values of delta P.

Albumins↗

Diffusion in gas exchange of insects.

The air-filled tracheal system constitutes the organ for gas exchange in terrestrial insects-its finest branches, the tracheoles, contacting individual cells. In the pupal stage, in which the animal lacks significant ventilatory movement, diffusion in the gas phase of the tracheal system constitutes the only mechanism for gas transfer between the environment and the tissues, transport in the hemolymph being insignificant. We have attempted to identify the main sites of diffusional resistance in the tracheal gas system by measuring the evolution of inert gases of low solubility from the pupa of the giant silkworm moth (Hyalophora cecropia). The results are compatible wih a single model in which the resistance to diffusional gas transfer in the tracheal system is concentrated at its opening at the body surface (spiracle).

Animals↗

Tracheal volume in the pupa of the Saturniid moth Hyalophora cecropia determined with inert gases.

Tracheal volume (VTr) was measured in pupae of the Giant silkworm moth Hyalophora cecropia (Saturniidae, Lepidoptera, Insecta) using inert gas wash-out techniques. The animal was placed in a small vessel that was continuously ventilated (rate, V) by a gas mixture containing 20% O2 in N2; the inflowing (F1) and outflowing gas fractions (FE) of the vessel could be continuously measured by a respiratory mass spectrometer. At the onset of a spiracular constriction period, which was evidenced from the FECO2 trace, the mixture was rapidly replaced by pure Ar. At the subsequent burst, the amount of N2 emerging from the animal, MN2, was calculated from V and the difference (FE--F1)N2. VTr was calculated from MN2 and the N2 concentration in the tracheal system before constriction (assumed to equal that in the ventilating gas before replacement by Ar). Measurements were repeated with N2 and Ar replacing each other. VTr average 48 microliter . g-1 (range 39 to 59) for animals of 5.8 g average body weight (range 3.4 to 9.9), when inert gas solubility in body fluids was accounted for. Both size and stage in pupal development appear to affect VTr. These values show reasonable agreement with literature data, mostly obtained by emptying the tracheal gas space by mechanical compression.

Animals↗

Ecophysiological adaptations to dry thermal environments measured in two unrestrained Namibian scorpions, Parabuthus villosus (Buthidae) and Opisthophthalmus flavescens (Scorpionidae).

The daily changes in body temperature experienced by Parabuthus villosus (Buthidae), a scorpion found on the gravel plains around Gobabeb, Namibia, and by Opisthophthalmus flavescens (Scorpionidae), a dune-dwelling species from the same area, were measured under similar field conditions. Thermocouples implanted under the segments of the mesosoma measured maximum temperatures as high as 43 degrees C in the shade. Air temperatures reached a maximum of 33 degrees C during the daytime and a minimum of 12 degrees C at night. Very low metabolic rates compared with those of other nonsedentary invertebrates were recorded in both species; oxygen consumption ranged from 8 microL g-1 h-1 at 16 degrees C to 115 microL g-1 h-1 at 40 degrees C. A pulsed Doppler system was used to measure heart rate in situ in free-moving scorpions. At night, heart rate declined to about 4 beats min-1 in resting undisturbed scorpions. During daylight excursions and while scorpions hunted for food, heart rates as high as 180 beats min-1 were observed. Heart rate was linearly correlated with temperature in P. villosus, with a slope of 2.37 (Q10 = 2.18), but in O. flavescens only a limited correlation was observed, with a slope of 1.18 (Q10 = 1.69). In O. flavescens, heart rate showed hysteresis as body temperature rose during daylight and then decreased during the late afternoon and evening; the reverse was observed in P. villosus. In both species, haemocyanin-oxygen affinity was independent of temperature, with a higher oxygen affinity and a larger pH sensitivity in O. flavescens. The Q10's of oxygen consumption and heart rate are quite different in O. flavescens but not as different in P. villosus. Although changes in the cardiovascular system, such as stroke volume, may also play a role in meeting increased oxygen demand, the features of the haemocyanin oxygen transport system, such as the absence of temperature sensitivity and a marked pH sensitivity, can also influence the maintenance of VO2 under temperature stress. The differences in the normal thermal habitats of the two species may be used to explain the distinctions between the evolved physiological responses to temperature increase shown by the two species.

Acclimatization↗