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Biomedical subjects

J P Butler

Publications and source records attributed to J P Butler.

At least 73 records · Page 4Linked to original sources

Diastolic vibration improves systolic function in cases of incomplete relaxation.

BACKGROUND: Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved. METHODS AND RESULTS: Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation. CONCLUSIONS: These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.

Animals↗

Kinetics of phagocytosis and phagosome-lysosome fusion in hamster lung and peritoneal macrophages.

The time course of phagocytosis and phagosome-lysosome fusion (PLF) in lung and peritoneal macrophages (LMs and PMs) was measured. Lysosomes in unelicited hamster LMs and PMs were labeled with lucifer yellow. Macrophages then phagocytized heat-killed Saccharomyces cerevisiae (yeast) and were evaluated at several time points for the degree to which yeast particles were adherent vs. internalized and for the presence or absence of PLF as based on the presence or absence of lucifer yellow in yeast-containing phagosomes. A three-compartment model (adherent, ingested, fused) of independent phagocytosis and PLF was developed; the number of yeast particles in each compartment was counted, and rate constants for ingestion and fusion were determined. Comparison of rate constants showed that ingestion was significantly faster in PMs (0.047 +/- 0.005 min-1) than in LMs (0.016 +/- 0.005 min-1) (mean +/- pooled SEM; P less than 0.001). Similarly, PLF was significantly faster in PMs (0.109 +/- 0.013 min-1) than in LMs (0.046 +/- 0.013 min-1) (P less than 0.003).

Animals↗

Viscoelastic and motile properties of hamster lung and peritoneal macrophages.

The motile and rheologic properties of hamster lung and peritoneal macrophages (LMs and PMs) were examined by following the motions of magnetizable iron oxide (gamma-Fe2O3) particles contained within phagolysosomes of these cells. As a measure of intracellular motility, gamma-Fe2O3 particles in cells were magnetically aligned and the decay rate of the remanent magnetic field (RMF) in the direction of initial magnetization was monitored over time. Cytoplasmic rheology was measured by twisting the intracellular particles with a magnetic field (Btw) applied perpendicularly to the direction of initial magnetization. We measured changes in the RMF associated with application and removal of Btw. Intracellular motility in LMs and PMs was not significantly different (P greater than 0.20); similarly, cytoplasmic viscosity was not significantly different in LMs and PMs (P greater than 0.12); deformation on application of torque was significantly greater (P less than 0.0001) and elastic recoil on removal of torque was significantly smaller (P less than 0.0001) in PMs than in LMs; and by qualitative observation, the yield stress of cytoplasm (associated with a plastic, nonrecoverable deformation) was lower in PMs than in LMs. These results show that although cytoplasmic motion and viscosity are similar in the two cell types, PM cytoplasm is less stiff than LM cytoplasm as determined by yield stress.

Animals↗

Pressure profiles show features essential to aerodynamic valving in geese.

Inspiratory airflow in the avian lung completely bypasses the most cranial secondary bronchi (the ventrobronchi), and instead enters bronchi arising more caudally (the dorsobronchi). Dotterweich (1936) proposed that 'aerodynamic valves' prevented entry into the ventrobronchi. We have recently provided evidence that inspiratory aerodynamic valving in avian lungs depends on convective inertia in the primary bronchus (Banzett et al., 1987). Theoretical and physical models (Butler et al., 1988; Wang et al., 1988) showed that convective inertia could effect valving, but the effectiveness of valving at resting flows was less than that observed in the bird. This leads us to hypothesize that a segment of the primary bronchus is constricted, accelerating the gas and enhancing the convective inertia. To test this hypothesis in the present work we measured pressures throughout the airways and air sacs in anesthetized, pump-ventilated geese at different flow rates and gas densities. Our data show: (1) there is a large pressure drop in the primary bronchus close to the ventrobronchial junction, indicating the presence of a constriction; (2) this pressure drop increases with gas density and flow; (3) the convective inertia at this site is more than 10 times downstream opposing pressures. We conclude that the primary bronchus just cranial to the first ventrobronchus forms a constriction which accelerates inspired air. Furthermore, we conclude that the convective inertia of gas leaving this segment is sufficient to achieve inspiratory valving.

Animals↗

[New method for estimating left ventricular myocardial elasticity by vibration analysis].

We solved numerical solutions of Advani-Lee's equation, which treats free vibrations of fluid-filled spherical shells, and forms the basis for non-invasive estimation of left ventricular myocardial elasticity. Numerical results showed that elasticity is approximated by E = 86.5.a2.f2 (E: elasticity (dyn/cm2), a: internal radius (cm), f: eigen-frequency (Hz)). To examine the accuracy of this theoretical equation in estimating elasticity, we made 7 spherical shells of silicone rubber, and compared the estimated elasticity by this equation with that by a standard stretch test. The elasticity calculated by Advani-Lee's equation and by stretch test proved to be nearly identical. Therefore, we concluded that we can estimate the elasticity of a spherical shell using this equation. We calculated the myocardial elasticity at the first heart sound emission in 25 normal persons with a simplified (approximated form of) Advani-Lee's equation. The mean elasticity in normal subjects was (7.04 +/- 2.46) x 10(5) dyn/cm2.

Elasticity↗

Analysis of human exposure to benzo(a)pyrene via inhalation and food ingestion in the Total Human Environmental Exposure Study (THEES).

The Total Human Environmental Exposure Study (THEES) focuses on benzo(a)pyrene (BaP) as an example of a combustion-generated polycyclic aromatic hydrocarbon (PAH) compound. Primary pathways for environmental exposures to BaP are inhalation and ingestion. This program of field studies was conducted in Phillipsburg, New Jersey, a small, industrial city in the Delaware River valley. The study protocols included direct monitoring of BaP exposures via inhalation and ingestion pathways during three separate periods, each lasting 14 days. BaP concentrations in air were sampled at outdoor and in-home locations, with personal air sampling added during the latter two phases. Cooked food samples from each household were acquired, using a constant portion "second plate" of each meal prepared at home. Ambient levels were 4-10 times higher during the cold months compared with the late summer study period. Space heating and regional aerosol were major contributors to community levels of BaP in the air during the wintertime. Penetration of outdoor air, cooking activities, combustion appliances, and cigarette smoke were important sources of indoor air exposures. Cooking activities, besides releasing BaP-enriched particles indoors, produced food imbued with BaP and added substantially to exposure via the ingestion route. Among the study subjects, the range and magnitude of dietary exposures (2 to 500 ng/d) were much greater than for inhalation (10 to 50 ng/d). Nevertheless, there were ample individual cases where inhalation of BaP was the predominant exposure route. Indoor air BaP levels were closely correlated with ambient levels in most of the homes. For some individuals, measured personal air BaP exposures were adequately predicted by time-weighting of microenvironmental (i.e., outdoor and in-home) concentrations. However, enormously high exposures for ingestion or inhalation were detected only by direct observation, not from microenvironmental data.

Administration, Inhalation↗

Evaluation of the relative contribution of exposure routes in a health risk assessment of dioxin emissions from a municipal waste incinerator.

Polychlorinated dioxins (PCDDs) and furans (PCDFs) are perceived by the public as the most hazardous materials emitted from municipal waste incinerators. These compounds disperse in the atmosphere and deposit on environmental media, where they may bioconcentrate in the food chain, resulting in a number of potential sources for human exposure. We performed a cancer risk assessment of PCDD/PCDF emissions from a municipal waste incinerator to evaluate the relative contribution of various exposure routes. Three scenarios were examined, all of which predicted ingestion of fish to be a significant source of exposure. In the common case, representative of the general population consuming mainly foods from commercial sources, inhalation was predicted to be the source of greatest exposure, followed by ingestion of fish, beef, milk, vegetation, and soil. In addition to fish, milk and beef ingestion contributed significantly to total exposure under the highly-exposed and worst case scenarios. Life-time cancer risk from the emitted PCDD/PCDFs was assessed for each scenario and was estimated as 1.8 x 10(-7) (common case), 2.5 x 10(-6) (highly-exposed case), and 6.7 x 10(-6) (worst case). In view of the conservative assumptions used in the assessment, the relatively low magnitude of these risks suggests that the PCDD/PCDF emissions from this incinerator should not be considered a significant public health concern.

Air Pollutants↗

Gas exchange across avian eggshells oscillates in phase with heartbeat.

Rahn et al. (J. Appl. Physiol. 69: 1546-1548, 1990) showed that the gas pressure in a plethysmograph containing an intact egg oscillates in phase with electrocardiogram (ECG) and that this pressure variation could be used as a noninvasive way to determine the heart rate of an avian embryo. One possible mechanism to account for the pressure oscillation is the mechanical movement of the embryonic heart, which leads to volume shifts of gas within the plethysmograph. Another possibility is that the oscillation of gas pressure with heartbeat is pulsatile gas exchange resulting from pulsatile blood flow. If gas exchange were transiently stopped, a pressure signal dependent on gas exchange should disappear, while a pressure signal dependent on cardiovascular motion should persist. Using a number of late-age hen eggs (at days 15-20 of incubation), we tested these hypotheses by suddenly changing the gas composition surrounding an egg and measuring the effect of the pressure oscillation. We found that 1) after 5% CO2-95% N2 was flushed into the plethysmograph (presumably halting gas exchange), pressure oscillations went almost to zero and the ECG signal remained; after air was flushed back to the plethysmograph, the pressure signal returned to control level; 2) after 20% CO2-20% O2-60% N2 was flushed into the plethysmograph (presumably increasing net gas exchange), the pressure signal increased 2.5-fold compared with that in air; and 3) after 1% CO2-99% N2 was flushed into the plethysmograph (presumably reversing gas exchange), the oscillation pressure decreased to one-fourth of that in air and the phase of pressure relative to ECG reversed compared with the phase in air.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pressure↗

Interpulse interval of GnRH stimulation independently modulates LH secretion.

To examine the importance of the interpulse interval of gonadotropin-releasing hormone (GnRH) stimulation in modulating gonadotroph responsiveness, a fixed individualized dose of GnRH was administered to eight GnRH-deficient men at intervals selected randomly from the distribution of luteinizing hormone (LH) interpulse intervals of normal men. The responses were compared with data derived from a study of LH pulses in 20 normal men. A positive relationship was found between LH pulse amplitude and the preceding interpulse interval both in the GnRH-deficient (P less than 0.05) and in the normal (P less than 0.003) men. The distributions of LH pulse amplitudes appeared to differ between the two groups with failure of the study paradigm to reproduce the distribution of low-amplitude pulses of the normal men in the GnRH-deficient men. There was significantly more variability about the line that related interpulse interval and LH amplitude in the normal men (P less than 0.004) in whom the amount of GnRH could vary physiologically. This difference remained significant both for pulses with amplitudes below (P less than 0.01) or above (P less than 0.03) the mean of the normal men. These studies demonstrate that the GnRH interpulse interval is an independent determinant of pituitary responsiveness and that alterations in the amount of GnRH secreted from the hypothalamus are an important determinant of LH pulse amplitude in men.

Adult↗

Amplification of airway constriction due to liquid filling of airway interstices.

Luminal epithelial projections formed during bronchoconstriction define interstices in which liquid can collect. Liquid in these interstices could amplify the degree of luminal compromise due to muscular contraction in at least two distinct ways. First, the luminal cross-sectional area is reduced by simple filling of the interstices. Second, if the surface tension (gamma) of the air-liquid interface is positive, the pressure drop across the interface produces an additional inward force that can further constrict the airway. We present a theoretical treatment of these two mechanisms together with data which suggest that both may significantly amplify the luminal narrowing due to airway smooth muscle contraction, particularly in small airways when gamma is high. To qualitatively assess the effects of altered gamma, guinea pig lungs with normal and altered airway liquid lining layers were frozen and studied while fully hydrated by low-temperature scanning electron microscopy. Airway gamma was altered in these animals by intratracheal instillation of 0.5 mg lysoplatelet-activating factor (lyso-PAF). The interstices of normal airways were dry, whereas the interstices of airways with altered surface lining layers were liquid filled. In addition, the surfactant inhibitory properties of lyso-PAF, 2-arachidonyl-PAF, and dipalmitoyl phosphatidylcholine (DPPC) were measured with a pulsating bubble surfactometer, using surfactant TA as the model surfactant. Minimal gamma (gamma min) of surfactant TA alone was 4.0 +/- 0.2 dyn/cm; a 5% mixture of lyso-PAF with surfactant TA resulted in a significantly (P less than 0.02) greater gamma min of 8.8 +/- 1.8 dyn/cm. In contrast, 2-arachidonyl-PAF and DPPC had minimal effects on gamma min of surfactant TA.

Animals↗

Step response of lung surface-to-volume ratio by light-scattering stereology.

By means of backscattered light from a pointlike source on the pleural surface, we investigated the dynamic behavior of the surface-to-volume ratio (S/V) in excised dog lobes subjected to small volume steps both in and out on both the inflation and deflation limb of standard pressure-volume maneuvers. The technique utilizes the established correlation of the pattern of backscattered light with morphometric mean linear intercept and is suitable for dynamic studies. We hypothesized that 1) there would be a difference in the timing of stress relaxation or recovery between alveolar septa and the fibromuscular tissue in the alveolar duct that would reveal itself as a temporally changing S/V after a step-volume change and 2) that geometric hysteresis (looping of S/V with volume), as seen with large volume excursion histories, would be similarly present in small tidal volume loops. Our experimental results contradicted both hypotheses. In particular, we found virtually no change in S/V after a step-volume change, even in the presence of substantial stress adaptation. In addition, when geometric hysteresis of small loops was present, it was always in the sense opposite to the geometric hysteresis of large loops. We conclude that 1) there is a functional "matching" of the stress-adaptive timing between alveolar septa and ductal mouths and 2) during small volume looping, the stress hysteresis (looping of stress with volume) in the ductal tissue may be larger than that of the septa, including surface tension.

Animals↗

Lengths and topology of alveolar septal borders.

To clarify the mechanics of alveolar parenchyma, we undertook a stereological and topological study in perfusion-fixed canine lungs of the borders of alveolar septa. We defined the principal borders as those along which one septum 1) joins two others (J), 2) joins one other at a distinct angle (B), or 3) joins no other structure (E). E and B borders are invariably reinforced with heavy connective tissue cables; J borders are not. Relative net lengths, determined from the number of traces per section area, were J, 45%; E, 19%; and B, 25%. These were remarkably constant over 10 canine lobes (5 animals, 4 volumes). Parenchyma, then, departs from the simple models that comprise only Js and Es. Bs are important; their net length exceeds that of Es. With lobe deflation, E shortened somewhat more than required to maintain geometric similarity, suggesting that the alveolar duct contracted disproportionately. A three-dimensional reconstruction was made from serial sections, and individual border segments were followed through the reconstruction. Typical lengths of individual J, B, and E borders were nearly equal. To characterize how the network of borders were interconnected, we counted the nodes at which they meet by class, e.g., EBE for the meeting of one B, two Es. The most common are JJJJ, 26%; EEEJ, 10%; EBJ, 24%; EBE, 8%; BBJJ, 12%. If parenchyma were constructed only from free-standing entrance rings and septal junctions, only JJJJ and EEEJ would be anticipated. The presence of EBJ, EBE, and BBJJ underscores parenchymal complexity. Only 7% of septa examined were bordered entirely by Js. Connective tissue cables were not confined to the alveolar duct's lumen but often extended to the primary septa at the periphery of the ductal unit. They rarely linked adjacent alveolar ducts; only 1 in 200 cable segments crossed from one duct to another. These observations support the concept that the parenchyma is an elastic network, characterized in part by a serial mechanical linkage from connective tissue cable to septal membrane to cable again.

Animals↗

Inspiratory valving in avian bronchi: aerodynamic considerations.

The presence of unidirectional flow in the avian lung is thought to be effected by aerodynamic 'valves'. First we review the history of this hypothesis and summarize existing evidence. Second, we present a semiquantitative treatment of the various fluid dynamic factors that may be involved in directing fluid flow. The resulting calculations show in some detail how the inspiratory valve may work, and upon what mechanisms it may depend. Our calculations suggest that gas convective inertial forces are sufficient to effect inspiratory valving. Finally, we give some heuristic arguments regarding the mechanisms of expiratory valving.

Animals↗

Bird lung models show that convective inertia effects inspiratory aerodynamic valving.

We assessed various aerodynamic factors which might influence inspiratory valve function in the avian lung. During inspiration, no flow enters the proximal segments of the ventrobronchi connecting the primary bronchus to cranial sacs. Instead, all flow in the primary bronchus continues through the mesobronchus. This pattern of flow past the ventrobronchi into the mesobronchus is called inspiratory aerodynamic valving. Introducing steady inspiratory flows into simplified plastic models of a bifurcation, we altered geometry, downstream resistance, flow rate and gas density while we measured the resulting flow partitioning between downstream branches. We found that these models did reproduce the inspiratory valving phenomenon. Gas flow rate, gas density and geometry upstream of the bifurcation played important roles in flow partitioning, but the geometry and branching angles of the ventrobronchi did not. These findings are consistent with the idea that convective inertia of the inspiratory gas stream promotes preferential axial flow (Butler et al., 1988) and may be the principal mechanism accounting for inspiratory aerodynamic valving in the avian lung.

Animals↗

Alterations of the hypothalamic GnRH interpulse interval sequence over the normal menstrual cycle.

Luteinizing hormone (LH) is released in a pulsatile fashion from the anterior pituitary in response to hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Previous autocorrelation analysis of the sequence of interpulse intervals of LH secretion in normal men has supported the hypothesis that the underlying hypothalamic mechanism of GnRH secretion governing episodic LH release is a renewal process, indicating that hypothalamic "memory," if present, does not extend back further in time than the preceding secretory pulse. A similar analysis of pulsatile LH secretion was undertaken in 45 studies of normal women, obtained throughout the menstrual cycle. Analysis of these studies revealed a process consistent with renewal throughout the follicular and early luteal phases. However, this relationship appears to break down in the mid-to-late luteal phase, indicating that alternative feedback pathways provide an overriding influence on the underlying renewal process of hypothalamic GnRH secretion. Pulsatile progesterone secretion by the corpus luteum, which first emerges at this stage of the menstrual cycle, may be the agent responsible for this feedback.

Female↗

Dihedral angles between alveolar septa.

To determine the dihedral angle, alpha, at the characteristic three-way septal junctions of lung parenchyma, we examined photomicrographs of sections. The three angles, A, formed where three septal traces meet on section, were measured and found to range between approximately 50 and 170 degrees. Theoretical considerations predicted that the dispersion of alpha is much narrower than that of A. The mean of A and alpha is identically 120 degrees. The standard deviation of alpha was inferred from the cumulative distribution function of A. In lungs inflated to 30 cmH2O (VL30), the standard deviation of alpha was very small (approximately 2 degrees) and increased to approximately 6 degrees in lungs inflated to 0.4 VL30. These findings imply that at VL30 tensions exerted by septa are locally homogeneous (2% variation) and at lower lung volumes become less so (6% variation). At high distending pressures, tissue forces are thought to dominate interfacial forces, and therefore the local uniformity of tensions suggests a stress-responsive mechanism for forming or remodeling the connective tissues. The source of the local nonuniformity at lower volumes is unclear but could relate to differences in mechanical properties of alveolar duct and alveoli. Finally, local uniformity does not imply global uniformity.

Animals↗

Dependence of instantaneous transfer function on regional ischemic myocardial volume.

To obtain the instantaneous left ventricular transfer function curve (instantaneous TFC) under conditions of regional ischemia, sinusoidal accelerations ranging from 30 to 150 Hz were applied to a small area of the epicardium of cross-circulated isovolumic canine left ventricle, and the contralateral acceleration was measured under control and during regional coronary occlusion (n = 11). The TFC is the ratio of the output to input acceleration amplitudes. The instantaneous TFC was characterized as a single-peaked configuration under control coronary perfusion. However, TFCs progressively changed from a single-peaked to a double-peaked configuration during regional ischemia. To quantify this change in instantaneous TFC, we defined an index D as the mean squared difference of TFC during ischemia from TFC during control. Index D was linearly related to the percent mass of the ischemic region at 40 minutes after onset of ischemia. We conclude that 1) transfer function curves are sensitive measures of myocardial heterogeneity and 2) the fractional ischemic weight of the ventricle is a major factor in determination of the deformation in instantaneous TFC at the later stages of regional ischemia.

Animals↗

The left ventricular vibration mode in the ventricular transfer function method and at the moment of the first heart sound.

Several investigators have aimed to clarify the patient's left ventricular (LV) physical properties by free vibration analysis of heart sound. Recently we have developed a transfer function (TF) method to calculate the LV viscoelasticity. To clarify whether this TF method and a clinical first heart sound (1 HS) analysis are based on the identical ventricular vibration mode analysis, we examined (1) the visualized LV vibration image in the TF method and (2) the quantitative relationship between the peak frequency of the 1 HS spectrum and that of TF curve in the early and late phase of the 1 HS. Isolated isovolumic potassium arrested canine left ventricles were used to visualize the vibration mode in describing the TF (N = 2). Examination of stroboscopically illuminated, slow-motion images revealed the oscillation of the ventricle to be of mode 2 behavior. To analyze the quantitative relation between the TF method and 1 HS analysis we used ten open-chest dogs. The correlation was good (r = 0.917) when the peak frequency of the TF curve at the early phase of the 1 HS was compared to the peak frequency of the 1 HS. We concluded that both the TF method and 1 HS analysis were based on the common, second-order ventricular vibration mode. Therefore, some information on the ventricular physical properties suggeted by the TF method could also be included in the clinical data obtained by 1 HS analysis.

Animals↗