Showing papers in "Annals of Biomedical Engineering in 1983"

The interface zone of inorganic implants in vivo: Titanium implants in bone.

Abstract: The interface zone between titanium implants and bone is considered at the macroscopic, microscopic, and molecular levels. A high rate of successful dental implants of pure titanium is associated with a very close apposition of the bone to the titanium surface, called osseointegration. At the macroscopic level, osseointegration allows efficient stress transfer from the implant to the bone without abrasion or progressive movement that can take place if a fibrous layer intervenes. At the microscopic level, surface roughness and porosity provide interlocking of the implant and bone tissue which grows into direct contact with titanium. Sections studied in the electron microscope show that calcified tissue can be identified within 50 A of the implant surface. The interface zone includes a tightly adherent titanium oxide layer on the surface of the implant which may be similar to a ceramic material in relation to tissue response. The five year success rate of 90% in 2895 implants in clinical trials since 1965 is associated with the favorable behavior of bone tissue at the interface zone with pure titanium.

A bidomain model for anisotropic cardiac muscle.

Abstract: Cardiac muscle is considered to consist of an intracellular domain and an exracellular or interstitial domain. Current passes from one domain to the other through the cell membrane. Electric potentials in interstitial space are shown to be associated with current sources proportional to the spatial gradient of the cellular transmembrane action potential, φ m . Hence, given the distribution of φ m throughout the myocardium, one can calculate the surface electrocardiogram and extracorporeal magnetocardiogram. The problem is considerably complicated when anisotropy is considered. If interstitial space is approximately isotropic, however, the sources are still proportional to ∇φ m . It is shown that the effects of intracellular anisotropy on the surface electrocardiogram may be relatively small. The inverse problem is discussed briefly, with consideration of the relationship of the magnetocardiogram to the electrocardiogram. Finally, it is shown that if the heart can be considered to be bounded by a closed surface, then the value of φ m on this surface is uniquely related to the surface electrocardiogram to within a constant, provided there are no internal discontinuities. Such discontinuities, however, would be expected to occur in cases of ischemia and necrosis.

Surface characterization of biomaterials by electron spectroscopy for chemical analysis.

Abstract: Electron spectroscopy for chemical analysis (ESCA) is perhaps the most valuable single method available for characterizing the surfaces of biomaterials. The ESCA analytical method is rich in information, observes a relevant surface region, and has been shown to generate results that correlate with biological response. In this article, the analysis of actual ESCA data is illustrated by reviewing a study in which polymer-coated glass surfaces, prepared for use as tissue culture substrates, are examined by ESCA. The application of more advanced ESCA techniques such as angular-dependent analysis to this situation is also considered. Finally, published applications of ESCA to the study of polyurethanes, hydrogels, protein films, cell culture substrates, and dental materials are briefly reviewed.

The mechanical and stress adaptive properties of bone.

Abstract: The properties of bone tissue as a material and bones as the structural elements of the skeleton are reviewed and summarized The first half of this work describes bone tissue microstructure, the stress-strain relations, and the strength and fracture of bone The second and slightly larger half concerns the adaptation of living bone tissue to its load environment Some observations and experiments of bone remodeling due to applied stress are described and continuum models for this process are formulated An example of bone remodeling leading to shape changes in the bone is described as well as an example of bone remodeling leading to changes in the bulk density of the bone tissue

A fiber optic PCO2 sensor

Abstract: The theory, construction and performance of a catheter tip optical PCO2 probe is described. The sensor, called the Opticap, is made with plastic fiber optics. One fiber carries light to the sensitive tip which is a silicone rubber tube 0.6 mm dia. X 1.0 mm long filled with a phenol red-KHCO3 solution. Ambient PCO2 controls the pH of the solution which influences the optical transmittance of the phenol red. A second fiber carries the transmitted signal to a receiver; the resulting electrical signal is linearly related to the PCO2 over the range of 2.7 to 10.7 kPa. The probe was tested as a tissue PCO2 sensor on the cerebral cortex of the cat and as an arterial PCO2 sensor. Drift over one day's use was 0.6 KPa or less and individual probes have been used as long as 12 weeks.

Intercalated discs as a cause for discontinuous propagation in cardiac muscle: A theoretical simulation

Abstract: A theoretical model of a cardiac muscle fiber (strand) based on core conductor principles and which includes a periodic intercalated disc structure has been developed. The model allows for examination of the mechanism of electrical propagation in cardiac muscle on a microscopic cell-to-cell level. The results of the model simulations demonstrate the discontinuous nature of electrical propagation in cardiac muscle and the inability of classical continuous cable theory to adequately describe propagation phenomena in cardiac muscle.

The discontinuous nature of electrical propagation in cardiac muscle. Consideration of a quantitative model incorporating the membrane ionic properties and structural complexities. The ALZA distinguished lecture.

Abstract: The propagation of excitation in cardiac muscle has generally been treated as though it occurred in a continuous structure. However, new evidence indicates that propagation in cardiac muscle often displays a discontinuous nature. In this paper, we consider the hypothesis that this previously unrecognized type of propagation is caused by recurrent discontinuities of effective axial resistivity which affect the membrane currents. The major implication is that the combination of discontinuities of axial resistivity at several size scales can produce most currently known cardiac conduction disturbances previously thought to require spatial nonuniformities of the membrane properties. At present there is no appropriate model or simulation for propagation in anisotropic cardiac muscle. However, the recent quantitative description of the fast sodium current in voltage-clamped cardiac muscle membrane makes it possible, for the first time, to apply experimentally based quantitative membrane models to propagation in cardiac muscle. The major task now is to account for the functional role of the structural complexities of cardiac muscle. The importance of such a model is that it would establish how the membrane ionic currents and the complexities of cell and tissue structure interact to determine propagation in both normal and abnormal cardiac muscle.

Surface tension of animal cartilage as it relates to friction in joints.

Abstract: Measurements of the surface tension of articular cartilage and friction experiments were carried out to provide further evidence in support of a new theory regarding the mechanism of friction in joints. To determine the surface tension of cartilage, contact angle measurements were used in conjunction with the equation of state for interfacial tensions. The advancing contact angle between saline drops and articular cartilage was found to be 100°±5°, indicating a highly hydrophobic surface. The corresponding surface tension value was calculated to be 22.5 ergs/cm2. Friction of cartilage against hydrophobic surfaces is shown to be lower than the friction of cartilage against hydrophilic surfaces. All these results further support the theory that lubrication by nonwetting drops occurs in joints and may be responsible for the exceptional friction characteristics of the joints.

A simple model for simulation of oxygen transport in the microcirculation

Abstract: A mathematical model of deoxygenation of blood in the microcirculation is used to estimate the mass transfer resistance in the blood and to examine certain assumptions used in prior work on simulation of the microcirculation: the treatment of blood as a continuum and the use of a single-step reaction kinetics model. The erythrocytes are treated as cylindrical slugs which alternate with plasma gaps such that oxygen transport is by radial diffusion in the cell. The system of equations including reaction kinetics and oxyhemoglobin diffusion is solved numerically. The results are of direct applicability in estimation of oxygen concentration profiles in tissue. The results also indicate that the resistance to oxygen transport in the capillary (relative to that in the surrounding tissue) is much higher than predicted by the continuum approach used by most prior workers. The resistance in the capillary is a significant fraction of the overall resistance. Other results give quantitative estimates of the error incurred from use of a single-step kinetic model.

Computer simulation of metabolism in palmitate-perfused rat heart. II. Behavior of complete model.

Abstract: Intermediary metabolism in rat hearts perfused with 11 mM glucose plus 1 mM palmitate was simulated by a computer model. Several enzyme submodels in a previous version of the isolated rat heart computer model were improved, and a new fatty acid oxidation pathway model was added. Compartmentation of metabolites in a pseudo-stationary state was calculated, and its implications are discussed, e.g., citrate level may not regulate glycolysis because it is mostly mitochondrial. Citrate synthetase, controlled largely by its inhibitors, is of key importance in regulating fatty acid metabolism. The response of aconitase to the mitochondrial Mg2+ level is of major importance in setting both the mitochondrial citrate and isocitrate levels. Pyruvate dehydrogenase is about 96% in the inactive phosphorylated form, and the active form is also 15% inhibited by products, severely limiting pyruvate oxidation and causing preferential utilization of palmitate as the metabolic fuel. The simulation is consistent with a creatine phosphate shuttle which delivers high energy phosphate to the site of its utilization for mechanical work.

Computer simulation of metabolism in palmitate-perfused rat heart. I. Palmitate oxidation

Abstract: A computer model of the fatty acid oxidation pathway in perfused rat heart was constructed. It includes uptake, activation, and β-oxidation of fatty acids, triglyceride synthesis and hydrolysis, and carnitine-dependent transport of acyl groups across the mitochondrial membrane under pseudosteady state conditions. Fatty acid utilization may be limited by β-oxidation in hypoxia or ischemia but probably not in aerobic conditions. Nonesterified fatty acids bound to proteins are found to be metabolically available. The model predicts that stearate, but not palmitate, can support the highest observed respiration rate for perfused rat heart without supplementation by other substrates. Fatty acids are preferentially oxidized rather than being stored as triglycerides because the cystosolic acyl CoA level is lower than the Km for triglyceride synthesis. It is suggested that feedback inhibition of triglyceride lipase regulates utilization of triglycerides as fuel in aerobic hearts.

Acrylic bone cement: in vitro and in vivo property-structure relationship--a selective review.

Abstract: The nature and curing characteristics of acrylic bone cement are presented to give some basic understanding of the key to improving its performance in in vivo clinical use. The use of electron paramagnetic resonance (EPR) spectroscopy in the (polymerization) setting and curing/aging of bone cement under in vitro and in vivo conditions is presented. The current research effort to improve the implant fixation by precoating the prosthesis with acrylic polymers is also discussed.

Implications of structure and geometry on cardiac electrical activity

Abstract: Electrical activity in the heart is dependent on the structure of the cellular components and their appositional geometry. The cells of the conduction system in mammals have a structure favoring faster conduction vis a vis the common working cells of the ventricles, which is further enhanced in large mammals and, significantly, in birds by an increase in cell diameters and tight packing of the component cells into large bundles. Tight packing also generates very narrow intercellular clefts that because of accumulation and depletion phenomena may contribute significantly to the measured electrical activity. Conduction cells may exist in mammalian atria analogous to their presence in bird atria, their electrical activity being possibly influenced by their diffuse anatomical integration with the common atrial working cells. Cell and bundle connections appear to be frequent within one length constant.

Steady-state analysis and evaluation of a new thermal sensor for surface measurements of tissue perfusion

Abstract: The steady-state response and operating characteristics of a new thermal sensor for surface measurements of local tissue perfusion have been analyzed theoretically and evaluated in vivo. The flow measurement system incorporates an electrically isolated thin-film thermal sensor, which is maintained at a fixed temperature by high frequency response electronic circuitry. The sensor rests on the tissue surface, and the power required to maintain a fixed probe to tissue temperature elevation is measured and related to tissue blood flow. A theoretical analysis of the steady-state probe response to flow changes was carried out employing the bio-heat-transfer equation and a solution based on Fourier series to describe the temperature distribution within the tissue domain. A comparison of steady-state theory to results obtained from initial experimental tests on the surface of the dog heart, over a perfusion range 0.51 to 2,00 ml/min/g, shows close agreement. The probe demonstrates good sensitivity to flow changes, provides stable and continuous measurements, and appears promising for both research and clinical applications.

Trophic effect of the sympathetic nervous system on vascular smooth muscle

Abstract: While the vasomotor effect of the sympathetic nervous system (SNS) on the arterial wall is well recognized, its trophic function is not. It is the aim of these studies to demonstrate this all-important function as it relates to the vascular muscle. Although the exact mechanism by which sympathetic nerve impulses influence the metabolism of the vessel wall is unknown, effects of sympathectomy can be demonstrated. Several lines of evidence indicate that chronic absence of sympathetic innervation in rabbits increases collagen synthesis and decreases activity of tricarboxylic acid cycle enzymes in the vascular wall. When chemically sympathectomized rabbits were fed a 1% cholesterol dietary supplement for 80 days, the aortas of these rabbits contained significantly more cholesterol and total lipids than those from fully innervated controls in spite of insignificant differences in plasma lipids. In a subsequent series of experiments we analyzed the efficacy of the SNS in two strains of pigeons. White Carneau (WC) pigeons are known by the susceptibility to atherosclerosis of the aorta while Show Racer (SR) pigeons are not. Our results demonstrate that the abdominal aorta of WC pigeons has less sympathetic innervation and it declines faster with age than that of SR pigeons. The results of the described studies documenting the direct trophic influence of the SNS on the arterial wall are reinforced by the similarity to the vessel wall changes induced by partial sympathectomy and natural ageing.

Ultrastructure, function and composition of smooth muscle.

Abstract: Filamentous myosin is present in both relaxed (myosin light chains unphosphorylated) and contracted (light chains phosphorylated) vascular smooth muscle The organization of myosin and actin filaments and the insertion of the latter on cytoplasmic and plasma membrane bound dense bodies is consistent with a mini sarcomere-like organization and a sliding filament mechanism of contraction in smooth muscle Mitochondria are high capacity, low affinity Ca stores in smooth muscle They do not play a role in the regulation of cytoplasmic Ca2+ at physiological levels The localization and Ca content of the junctional sarcoplasmatic reticulum (SR) is consistent with this organelle being the major intracellular source of activator Ca released by excitatory transmitters Repeated contractions in the absence of extracellular Ca2+ (thought to represent recycling of intracellular activator Ca2+) can be demonstrated if the excitatory agent is not allowed to remain in contact with the smooth muscle throughout relaxation; the demonstration of "recycling" is facilitated if the efflux of cellular Ca2+ is blocked The rise in total cytoplasmic calcium measured with electron probe analysis during a maintained (30 min) contracture in rabbit portal-anterior mesenteric vein smooth muscle (approximately 09 mol/kg dry cytoplasm) is greater than the amount of Ca that could be bound to calmodulin

An experimental evaluation of the use of an ensemble average for the calculation of turbulence in pulsatile flow

Abstract: A comparison was made between turbulence calculated by subtracting an ensemble average from the instantaneous velocity and calculations made with a high pass digital filter. Velocity was measured with a laser Doppler anemometer in vitro in the region of a normal porcine aortic valve and in patients with a hot film anemometer in the region of normal aortic valves. From the velocity obtained in patients, the absolute turbulence intensity calculated using an ensemble average of 50 beats was nearly twice the turbulence intensity calculated using a digital filter. Individual beats sometimes showed differences of 150% compared to calculations based upon the use of a digital filter. Inspection showed that the ensemble average varied widely from the actual nonfluctuating velocity. Studies in vitro showed less beat to beat variation than occurred in patients. The absolute turbulence intensity measured in vitro, when calculated using an ensemble average, was only 20% greater than calculations using a digital filter. The differences were due primarily to beat-to-beat variations of the nonfluctuating velocity, but these beat-to-beat variations were less prominent than occurred in patients. These observations suggest that ensemble averaging may not be appropriate for the calculation of turbulence, particularly in patients.

Analysis of the linear under-agarose leukocyte chemotaxis assay

Abstract: Random and chemotactic movement of leukocytes appear to be key processes in the host inflammatory response. Abnormalities in leukocyte motility and chemosensory behavior have been implicated in a large number of pathological conditions, but there is no adequate quantitative understanding of these properties. In this paper we present an approach for determination of phenomenological cell motility and chemotaxis parameters, by analysis of a common leukocyte migration assay. Using data from a set of cell migration experiments reported in the literature, we show how to determine the value of the random motility coefficient and its dependence upon concentration of a tripeptide chemotactic attractant, as well as the value of the chemotaxis coefficient, assumed here to be independent of attractant concentration. These parameters can be used to improve quantitative understanding of the relationship between leukocyte motility and chemosensory behavior and effective functioning of the host inflammatory response.

Computer simulation of metabolism in palmitate-perfused rat heart. III: Sensitivity analysis

Abstract: The behavior of a computer model of metabolism in glucose- and palmitate-perfused rat hearts was interpreted by sensitivity analysis to explain why the heart preferentially utilizes fatty acids as fuel even in the presence of substantial exogenous glucose. The sensitivity functions identified those metabolites and enzymes which were most important in regulating the metabolic rate and determined which enzymes set the levels of the critical metabolites. Control of the mitochondrial redox potential and the distribution of coenzyme A thioesters regulated the rate of fatty acid utilization while strong inhibition of citrate synthetase resulted in accumulation of acetyl CoA and supprersion of pyruvate oxidation. Glycolysis was limited by the cytosolic ATP/ADP ratio set largely by the creatine shuttle. Metabolic control appears to be widely distributed rather than localized at “key” enzymes. Metabolite levels are usually set by enzymes controlled by modifiers whereas metabolic flux is regulated by the enzymes that produce ligands for the modifier-controlled enzymes.

Measurement of sweating rate with capacitance sensors

Abstract: A new forced-evaporation type skin capsule for measuring local sweat gland activity in humans is described and details of its construction and problems of calibration are presented. The capsule is self-contained, portable, and inexpensive making it well suited for use in arrays to make multiple simultaneous determinations on adjacent skin areas. Sweat is evaporated from the skin surface by a stream of dry nitrogen gas; subsequent changes in capsule relative humidity and temperature are measured by a commercially available thin-film capacitance sensor and a solid-state current regulating device, respectively. These changes are measured within the capsule itself so no external water vapor analyzer is needed. Data acquisition and evaporation rate calculations are handled by an on-line microcomputer.

Innervation of the cerebral vasculature.

Abstract: With the development of specific antibodies to vasoactive peptides and application of immunohistochemistry and radioimmunoassay methods, knowledge of vascular innervation has grown rapidly. In the cerebral circulation, four possible neurotransmitters are present: norepinephrine, acetylcholine, vasoactive intestinal peptide (VIP), and substance P. There is a dense adrenergic innervation of cerebral arteries, but contractile responses to nerve stimulation or circulating catecholamines are relatively small both in vitro and in vivo. Recent studies using radioligand binding techniques indicate a lack of specific 3H-prazosin binding in cerebral arteries, in contrast to other vascular beds. Thus a lack of alpha1-adrenergic receptors in cerebral arteries may account for weak responsiveness to sympathetic stimulation. Both VIP and acetylcholine may be vasodilator neurotransmitters, but blockade of cholinergic responses does not alter neurogenic vasodilation. The lack of specific VIP antagonists hampers efforts to explore this system more fully. Substance P-containing nerves are affected by capsaicin, supporting the hypothesis that these are primary sensory afferents, perhaps mediating pain. Future work in this area may focus on defining the pathways of these nerves and exploring the role of co-transmitters and possible interactions between nerves. With this basic information, experiments can be designed to elucidate more clearly the functional roles these nerves play.

Assessment of cerebrospinal fluid compliance and outflow resistance: Analysis of steady-state response to sinusoidal input

Abstract: Cerebrospinal fluid dynamics have been studied in the past by analyses of responses to bolus, constant rate or constant pressure inputs. In this study, we present a method for analyzing CSF pressure responses to sinusoidal variation in the infusion rate. Infusion of artificial CSF into the cisterna magna of adult rats was modulated sinusoidally between 0 and 30 μl/min. The resulting sinusoidal variation in intracranial pressure was recorded on a strip chart recorder simultaneously with the infusion rate signal. The two signals were analyzed for peak-to-peak variation, mean value, and phase shift for input frequencies in the range of 0.0015 to 0.01 Hz (0.00942 to 0.0628 radians/sec). The system was analyzed at each mean infusion rate as a parallel resistance and compliance with a first order linear model. The resistance to CSF outflow was determined as the change in mean steady-state pressure divided by the change in mean infusion rate. The compliance was then obtained from the frequency dependent phase shift between input and output using the first-order linear model. Resistance values were lower for higher average infusion rates consistent with our previous work, while compliance remained constant over the measured pressure range.

A computerized mass spectrometer and flowmeter system for respiratory gas measurements

Abstract: Instrumentation systems for breath-to-breath analysis of respiratory gas exchange have been faulted by phase lags between various flow and composition signals and by difficulties in gathering and processing large amounts of data. The system described here represents an attempt to overcome these problems. Phase delays have been minimized by using a direct, piezoelectrically operated mass spectrometer inlet rather than an inlet capillary, by locating the mass spectrometer inlet and flow sensors in the same plane, and by incorporating design features which enhance the mass spectrometer response. Convenience in system operation and data analysis has been enhanced by integrating a computer into the system design so that the computer performs on-line data analysis and control functions and provides the primary interface between the experimenter and the instruments. Miniaturization of the instruments permits close coupling to an exercising subject.

An improved method for water vapor detection

Abstract: We describe improvements in and details for the construction, calibration and use of a device using a thermal conductivity cell for the measurement of low-level rates of water evaporation (E) from a small surface area. E is measured from 0.0 to 1.0 mg·min−1 with a correlation coefficient of 0.999 between measured and independently verified rates and amounts of water evaporation. Data are available as a recordable analog d.c. voltage as well as in digital display for E and for the amount of water evaporated during an operator defined time period. The device we describe is noninvasive and it is designed to be constructed of conventional components. It is useful not only for measuring transcutaneous water diffusion in normal and diseased skin, but also it is adequately sensitive and rapidly responding to follow thermoregulatory and psychogenic sweating in small (nom. 1.0 cm2) skin areas. It can also be used to measure accurately and precisely the rates at which water is adsorbed by and removed from inanimate materials, as well as to determine how much water they store.

Model utility in the study of cardiorespiratory control.

Abstract: This study investigates the utility of differing modeling approaches to the study of cardiorespiratory control Models are classified in terms of intended purpose A structural model predicts behavior based on a hypothetical physiological structure An empirical model summarizes observed behavior A functional model attempts to relate physiological structure to observed behavior Models from the literature for exercising man illustrate these concepts and motivate the importance of experimental design in terms of the dynamic variation of a work-rate input

Excitation of vascular muscle by norepinephrine

Abstract: The mechanism by which norepinephrine causes excitation of vascular muscle is a concept that has undergone considerable change in the last several years. Although the excitation step is absolutely fundamental to understanding constriction and dilation of arteries, several aspects of the hypothesis are not well understood and have recently been controversial. The earliest view of the excitation process was that action potentials propagate uniformly along the arterial wall, just as in fast skeletal muscle, and was disproved early in recording of electrical events from blood vessel walls. The view that then emerged was that membrane potential acts as an analog signal controlling contraction through graded depolarization which, unlike that found in fast skeletal or cardiac muscle, could be maintained for minutes or even hours. This concept of graded depolarization and graded contraction has served as the best model of the vascular muscle excitation process for about 20 years. However, questions have been raised about the importance of membrane potential as a control mechanism because of reports of noncorrelations between membrane potential and tension. The controversy centers around two alternate proposals for the excitatory action of norepinephrine. The proposal of the noncorrelation group is that mechanisms other than membrane potential exert the major control over contraction, perhaps with spatially specialized receptors such that only those areas near nerve endings would cause depolarization as part of the event initiating contraction. On the other hand, the proposal by the strong correlation group would be that membrane potential is the dominant control mechanism. Where experiments have been carried out to specifically test the existence of a noncorrelation between membrane potential and contraction, no failure of correlation was found. The fundamental problem in each instance of a noncorrelation appears to be the attempt to record tension from one part of an artery and membrane potential from another part, which is assumed to behave as an electrically and mechanically homogeneous unit. However, direct measurements of localized areas of the blood vessel wall show such an assumption to be unjustified. In fact, cell-to-cell conduction of an electrical signal to synchronize the blood vessel could not be supported in experiments using refined intracellular and extracellular recording methods. These observations suggest that the attempt to understand the relationship between interaction of norepinephrine with the membrane and the contractile event is best approached as a single cell phenomenon, where assurance that electrical and mechanical recording is of the same process can be demonstrated. At least in the caudal artery of the rat, the spatial definition of contraction appears to be under the control of diffusion of norepinephrine. No important role for cell-to-cell conduction or for modification of the excitation process by any agent through changes in conduction has been demonstrated in vascular muscle. The extent of the arterial wall involved in a single contraction would appear to be defined by diffusion of norepinephrine from its release point.

Bloodless evaluation of blood oxygenators.

Abstract: Evaluation of blood oxygenators using whole blood is inconvenient and expensive, although it is the ultimate preclinical test. Sodium sulfite solutions have advantages over blood for studying oxygen uptake: They are inexpensive, fewer variables need control, and deoxygenation is unnecessary. Assays and interpretation of results are easy. The kinetics of sulfite oxidation must be fast and the concentration of sulfite must be low to emulate oxygen uptake by blood. The kinetics were studied yielding a first order rate constant in sulfite, zero order in oxygen, of 740/min. Limitations of the technique were evaluated using the experimental rate constant and an adaptation of Lightfoot’s approximation. While the reaction of hemoglobin is reversible and essentially instantaneous, that for sulfite is irreversible and finite. Thus if the approach to saturation is not monotonic or if the mass transfer resistance is significantly lowered, e.g., when blood film thicknesses are thinner than a few hundred microns, deviations may occur. Two TMO oxygenators and several prototypes were tested, with both sulfite and bovine blood. Uptakes of oxygen were comparable and the effect of parameter variations were similar. The use of sulfite for early evaluation of oxygenators is concluded to be very useful.

Measurement of regional myocardial perfusion using collimated miniature radiation detectors and the method of 133-Xenon washout

Abstract: A new approach to the measurement of local myocardial perfusion based on the application of highly-collimated miniature cadmium telluride radiation detectors to measure washout of 133-Xenon from well-defined tissue volumes is presented. Single-hole collimators with length/diameter ratios of 1 (L=4 mm, D=4 mm) and 4 (L=12 mm, D=3 mm) were employed as prototype designs. The probe field of view was characterized theoretically using a spherical model of the myocardium in conjunction with experimental point source response measurements for each collimator. Method evaluation using two medium resolution collimators (L/D=1) was effected by performing left main and circumflex coronary artery perfusion studies at controlled but variable flows in the dog heart. An excellent correlation (r>0.99) between actual and estimated perfusion determined from 65 washout curves over the flow range 0.38 to 3.18 ml/min/gm was demonstrated. The ability to resolve regional flow differences was verified by measuring tracer washout from circumflex and left anterior descending regions of the myocardium, using two high resolution collimators (L/D=4), in a preparation where the left main coronary artery was cannulated and a snare was placed around the circumflex coronary artery to selectively reduce flow to that region.

Mechanical behavior of vascular smooth muscle

Abstract: Strips of smooth muscle prepared from the media of arteries can provide favorable preparations for the in vitro assessment of contractile function due to their comparatively simple anatomy, control over excitatory and inhibitory input, the experimental and analytical simplicity of estimating length and stress, and their suitability for correlated biochemical measurements when quick-frozen during contractions. However, several stringent criteria must be met before these advantages can be realized. [1] The cells must be aligned in parallel in the axis in which measurements are made. [2] Cells anatomically in series must be mechanically coupled and uniformly activated if tissue measurements are to provide estimates of cellular mechanics. [3] The cross-section of the tissue must be constant, accurately measured, and the fraction consisting of smooth muscle cells determined. [4] The contractile system must be fully inactivated to determine the passive characteristics of the tissue. [5] Active mechanical properties should be normalized in absolute units allowing comparisons with other tissues, determination of the level of activation, and assessment of preparation viability. There are strong arguments for referencing length to the optimum length for stress generation (L0) even though some passive stress is present. Mechanical studies of several preparations meeting these criteria provide strong support for the applicability of the sliding filament/crossbridge mechanism to smooth muscles. This implies that the active stress determined at (Lo) (So) provides an estimate of the number or fraction of crossbridges which are interacting with thin filaments, and that isotonic shortening velocities estimated at zero external load (V0, obtained by extrapolation from force-velocity data) provide an estimate of average cross-bridge cycling rates. When mechanical studies of the media of swine carotid arteries are interpreted according to this paradigm, a number of properties distinguishing arterial smooth muscle from striated muscle have emerged. [1] The smooth muscle can develop twice the stress (So = 6.7 • 105 N/m 2 cell cross-section) achieved by skeletal muscle with a cellular myosin (and crossbridge) content some 4-fold lower. [2] The rise in myoplasmic [Ca ++] upon stimulation indirectly leads to contraction by activation of myosin light chain kinase and phosphorylation of the crossbridge. This is a rapid cellular event (< 5 sec, usually limited by diffusion rates in agonist-induced contractions) and is associated with much higher crossbridge cycling rates and shortening velocities than previously estimated. [3] All stimuli appear to produce an initial transient in the cell [Ca + +]. The subsequent decline to a lower maintained concentration is associated with decreases in both phosphorylation and shortening velocities. However, active stress is maintained by another regulatory mechanism with a greater sensitivity to Ca + +. Force maintenance with greatly reduced ATP consumption by dephosphorylated nonor slowly-cycling (very low V0) crossbridges (termed \"latch\") defines a second population of crossbridges in tonically contracting smooth muscle. (Supported by NIH Grant P01 HL 19242.)

Interaction of microporous glassy carbon and living tissue

Abstract: Preliminary animal implantation tests with rats showed that microporous glassy carbon has good biocompatibility. Microporous glassy carbon is also stable and suitable for a hard biocompatible implant.