TEMPERATURE AND CRITICAL ILLUMINATION FOR REACTION TO FLICKERING LIGHT : IV. ANAX NYMPHS

At fixed flash frequency (_F = 20, _F = 55) and with constant light time fraction (50 per cent) in the flash cycle, the critical illumination I for response of Anax nymphs to visual flicker falls continuously as the temperature rises. The temperature characteristic µ for the measure of excitability (1/I) increases continuously with elevation of temperature. The form of the F - log I curve does not change except at quite high temperature (35.8°), and then only slightly (near F = 55); F_max. is not altered. The very unusual form of the 1/I curve as a function of temperature is quantitatively accounted for if two processes, with respectively µ = 19,200 and µ = 3,400, contribute independently and simultaneously to the control of the speed of the reaction governing the excitability; the velocities of these two processes are equal at 15.9°.     

THEORY AND MEASUREMENT OF VISUAL MECHANISMS : V. FLASH DURATION AND CRITICAL INTENSITY FOR RESPONSE TO FLICKER

The relation between flash duration and mean critical intensity (white light) for threshold recognition of visual flicker, as a function of flash frequency, was investigated by means of measurements at five values of the light-time fraction: 0.10, 0.25, 0.50, 0.75, 0.90, with flash frequencies of the interrupted beam ranging from 2 to 60 per second. A square area, 6.1 x 6.1°, centrally fixated) was viewed monocularly; the discriminometer used provides automatically an artificial pupil 1.8 mm. in diameter. Except for the slight day-to-day fluctuation in the magnitudes of the parameters, the data for the observer used are shown to form an essentially homogeneous group. As for other animals tested, the F - log I_m curve is enlarged and moved toward lower flash intensities as the light-time fraction is decreased. The high intensity segments of the duplex curves are fitted by normal probability integrals for which F _max. and the abscissa of inflection are rectilinear functions of t_L(t_L + t_D), with opposite slopes. The third parameter, (σ''_{log I}, is invariant. The low intensity segments are composites, their shapes determined by the summation of the lower part of the high intensity curve with an overlapping low intensity population of effects. Both the rising and the declining branches of this latter assemblage suffer competitive partial suppression by the effects in the high intensity population. The detailed analysis shows that these results are consistent with the theory of the central, rather than peripheral, location of the dynamically recognizable elements in the determination of flicker.     

CRITICAL ILLUMINATION AND FLICKER FREQUENCY,AS A FUNCTION OF FLASH DURATION: FOR THE SUNFISH

From the relations between critical illumination in a flash (I_m) and the flash frequency (F) for response of the sunfish to visual flicker when the proportion of light time to dark time (t_L/t_D) in a flicker cycle is varied at one temperature (21.5°) the following results are obtained: At values of t_L/t_D between 1/9 and 9/1 the F - log I_m curves are progressively shifted toward higher intensities and lower F_max.. F_max. is a declining rectilinear function of the percentage of the flash cycle time occupied by light. The rod and the cone portions of the flicker curve are not shifted to the same extent. The cone portion and the rod region of the curve are each well described by a probability integral. In terms of F as 100 F/F_max. the standard deviation of the underlying frequency distribution of elemental contributions, summed to produce the effect proportional to F, is independent of t_L/t_D. The magnitude of log I_m at the inflection point (r''), however, increases rectilinearly with the percentage light time in the cycle. The proportionality between I_m and σ_II1 is independent of t_L/t_D. These effects are interpreted as consequences of the fact that the number of elements of excitation available for discrimination of flicker is increased by increasing the dark interval in a flash cycle. Decreasing the dark interval has therefore the same kind of effect as reducing the visual area, and not that produced by decreasing the temperature.     

THE ORIENTATION OF ANIMALS BY OPPOSED BEAMS OF LIGHT

When orientation is attained under the influence of beams of parallel light opposed at 180° the deflection θ from a path at right angles to the beams is given by tan See PDF for Equation, where I ₁ and I ₂ are the photic intensities and H is the average angle between the photoreceptive surfaces. This expression is independent of the units in which I is measured, and holds whether the primary photosensory effect is proportional to I or to log I. When photokinetic side-to-side motions of the head occur, H decreases with increasing total acting light intensity, but increases if higher total light intensity restricts the amplitude of random movements; in each case, H is very nearly proportional to log I ₁ I ₂. For beams of light at 90°, See PDF for Equation. The application of these equations to some particular instances is discussed, and it is shown why certain simpler empirical formulæ previously found by others yield fair concordance with the experimental data. The result is thus in complete accord with the tropism theory, since the equations are based simply on the assumption that when orientation is attained photic excitation is the same on the two sides.     

THE FLICKER RESPONSE CURVE FOR FUNDULUS

After Fundulus heteroclitus have been for some time in the laboratory, under conditions favorable for growth, and after habituation of the fishes to the simple routine manipulations of the observational procedure required, they are found to give reproducible values of the mean critical flash illumination (I_m) resulting in response to visual flicker. The measurements were made with equality of light time and dark time in the flash cycle, at 21.5°C. Log I_m as a function of flash frequency F has the same general form as that obtained with other fishes tested, and for vertebrates typically: the curve is a drawn-out S, with a second inflection at the low I end. In details, however, the curve is somewhat extreme. Its composite form is readily resolved into the two usual parts. Each of these expresses a contribution in which log I, as a function of F, is accurately expressed by taking F as the summation (integral) of a probability distribution of d log I, as for the flicker response contour of other animals. As critical intensity I increases, the contribution of rod elements gradually fades out; this decay also adheres to a probability integral. The rod contribution seen in the curve for Fundulus is larger, absolutely and relatively to that from the cones, than that found with a number of other vertebrates. The additive overlapping of the rod and cone effects therefore produces a comparatively extreme distortion of the resulting F-log I curve. The F-log I_m curve is shifted to lower intensities as result of previous exposure to supranormal temperatures. This effect is only very slowly reversible. The value of F _max. for each of the components of the duplex curve remains unaffected. The rod and cone segments are shifted to the same extent. The persisting increase of excitability thus fails to reveal any chemical or other differentiation of the excitability mechanism in the two groups of elements. Certain bearings of the data upon the theory of the flicker response contour are discussed, with reference to the measurements of variation of critical intensity and to the form of the F-log I curve. The quantitative properties of the data accord with the theory derived from earlier observations on other forms.     

THEORY AND MEASUREMENT OF VISUAL MECHANISMS : III. ΔI AS A FUNCTION OF AREA,INTENSITY, AND WAVE-LENGTH,FOR MONOCULAR AND BINOCULAR STIMULATION

Measurements of ΔI as a function of retinal area illuminated have been obtained at various levels of standard intensity I ₁, using "white" light and light of three modal wave-lengths (λ465, 525, 680), for monocular stimulation and for simultaneous excitation of the two eyes ("binocular"), using several methods of varying (rectangular) area and retinal location, with control of exposure time. For data homogeneous with respect to method of presentation, log ΔI_m = -Z log A + C, where ΔI = Ĩ ₂ – I ₁, A is area illuminated, and C is a terminal constant (= log ΔI_m for A = 1 unit) depending on the units in which ΔI and A are expressed, and upon I ₁. The equation is readily deduced on dimensional grounds, without reference to specific theories of the nature of ΔI or of retinal area in terms of its excitable units. Z is independent of the units of I and A. Experimentally it is found to be the same for monocular and binocular excitations, as is to be expected. Also as is expected it is not independent of λ, and it is markedly influenced by the scheme according to which A is varied; it depends directly upon the rate at which potentially excitable elements are added when A is made to increase. For simultaneous excitation of the two eyes (when of very nearly equivalent excitability), ΔĪ_B is less than for stimulation of either eye alone, at all levels of I ₁, A, λ. The mean ratio (ΔĪ_L + ΔĪ_R)/2 to ΔI^B was 1.38. For white light, doubling A on one retina reduces ΔI_m in the ratio 1.21, or a little less than for binocular presentation under the same conditions. These facts are consistent with the view that the properties of ΔI are quantitatively determined by events central to the retina. The measure σ_1ΔI of organic variation in discrimination of intensities and ΔI_m are found to be in simple proportion, independent of I ₁, A, λ (and exposure time). Variability (σ_1ΔI) is not a function of the mode of presentation, save that it may be slightly higher when both retinas are excited, and its magnitude (for a given level of ΔI_m) is independent of the law according to which the adjustable intensity I ₂ is instrumentally controlled.     

AREA AND VISUAL THRESHOLD

1. The variation of threshold with field area was measured in fields homogeneous in rod-cone composition. At 15° above the fovea, an increase in field diameter from 1° to 5° reduces the threshold sevenfold, at 25° above the fovea tenfold. 2. These changes are shown to follow qualitatively from simple statistical properties of the retinal mosaic. Analytic treatment leads to the expression, (A – n_t)^k I = C, in which A = area, n_t = constant threshold number of elements, I = threshold intensity, and k and C are constants. This equation describes the available data accurately, and is the general form of previous empirical area-threshold formulae.     

CRITICAL ILLUMINATION AND FLICKER FREQUENCY IN RELATED FISHES

Flicker response curves have been obtained at 21.5°C. for three genera of fresh water teleosts: Enneacanthus (sunfish), Xiphophorus (swordtail), Platypoecilius (Platy), by the determination of mean critical intensities for response at fixed flicker frequencies, and for a certain homogeneous group of backcross hybrids of swordtail x Platy (Black Helleri). The curves exhibit marked differences in form and proportions. The same type of analysis is applicable to each, however. A low intensity rod-governed section has added to it a more extensive cone portion. Each part is accurately described by the equation F = F_max./(1 + e ^{-p log-p logI/I_i}), where F = flicker frequency, I = associated mean critical intensity, and I_i is the intensity at the inflection point of the sigmoid curve relating F to log I. There is no correlation between quantitative features of the rod and cone portions. Threshold intensities, p, I_i, and F_max. are separately and independently determined. The hybrid Black Helleri show quantitative agreement with the Xiphophorus parental stock in the values of p for rods and cones, and in the cone F_max.; the rod F_max. is very similar to that for the Platy stock; the general level of effective intensities is rather like that of the Platy form. This provides, among other things, a new kind of support for the duplicity doctrine. Various races of Platypoecilius maculatus, and P. variatus, give closely agreeing values of I_m at different flicker frequencies; and two species of sunfish also agree. The effect of cross-breeding is thus not a superficial thing. It indicates the possibility of further genetic investigation. The variability of the critical intensity for response to flicker follows the rules previously found to hold for other forms. The variation is the expression of a property of the tested organism. It is shown that, on the assumption of a frequency distribution of receptor element thresholds as a function of log I, with fluctuation in the excitabilities of the marginally excited elements, it is to be expected that the dispersion of critical flicker frequencies in repeated measurements will pass through a maximum as log I is increased, whereas the dispersion of critical intensities will be proportional to I_m; and that the proportionality factor in the case of different organisms bears no relation to the form or position of the respective curves relating mean critical intensity to flicker frequency. These deductions agree with the experimental findings.     

THE FLICKER RESPONSE CONTOUR FOR THE FROG

The flicker response contour for the frog Rana pipiens exhibits the duplex character typical for most vertebrates. By comparison (under the same conditions of temperature, 21.5°, and light-time fraction, = 0.5), the low intensity section of the F - log I curve is the smallest thus far found. The cone portion of the curve is satisfactorily described by a probability integral. The rod part represents the addition of a small group of sensory effects upon the lower end of the cone curve, from which it can be analytically separated. The relation between the two groups of sensory effects permits certain tests of the rule according to which (in homogeneous data) I_m and σ_1I1 are in direct proportion.     

Effect of Low Sodium, Tetrodotoxin, and Temperature Variation upon Excitation

The lowering of external sodium raised both the constant quantity threshold, Q_o, and the rheobase, I_o, in both real space-clamped squid axons and the theoretical axon as computed on the basis of the standard Hodgkin-Huxley equations. In both real and theoretical axons the minimum intensity for excitability for short pulses, which occurs at about 15°C, was still present when low sodium replaced seawater. Low sodium did not affect the temperature dependence of the strength-duration relationship in the range, 5° to 25°C. The excitability of tetrodotoxin-treated real axons was found to be more temperature-dependent than that of normal real axons. Also the data on dosage-response to TTX of real axons fit the dose-response relationship of a hypothetical system in which one TTX ion binds reversibly to its receptor to produce a fraction of the inhibitory effect, the curve being identical to a simple adsorption isotherm. The Hodgkin-Huxley equations describe the broad outline of events occurring during excitation quite well.     

THEORY AND MEASUREMENT OF VISUAL MECHANISMS : X. MODIFICATIONS OF THE FLICKER RESPONSE CONTOUR,AND THE SIGNIFICANCE OF THE AVIAN PECTEN

1. When there is projected on the retina (man, monocularly) the shadow of a grid which forms a visual field in several distinct pieces (not including the fovea in the present tests), the ordinary properties of the flicker recognition contour (F vs. log I) as a function of the light-time cycle fraction (t_L) can be markedly disturbed. In the present experiments flicker was produced by the rotation of a cylinder with opaque vertical stripes. In the absence of such a grid shadow the "cone" segments of the contours form a set in which F_max. and the abscissa of inflection are opposite but rectilinear functions of t_L, while the third parameter of the probability integral (σ''_{log I}) remains constant. This is the case also with diverse other animals tested. In the data with the grid, however, analysis shows that even for low values of t_L (up to 0.50) there occurs an enhancement of the production of elements of neural effect, so that F_max. rises rather than falls as ordinarily with increase of t_L, although σ''_{log I} stays constant and hence the total number of acting units is presumed not to change. This constitutes valid evidence for neural integration of effects due to the illumination of separated retinal patches. Beginning at t_L = 0.75, and at 0.90, the slope of the "cone" curve is sharply increased, and the maximum F is far above its position in the absence of the grid. The decrease of σ''_{log I} (the slope constant) signifies, in terms of other information, an increase in the number of acting cone units. The abscissa of inflection is also much lowered, relatively, whereas without the grid it increases as t_L is made larger. These effects correspond subjectively to the fact that at the end-point flicker is most pronounced, on the "cone" curve, along the edges of the grid shadow where contrast is particularly evident with the longer light-times. The "rod" portion of the F - log I contour is not specifically affected by the presence of the grid shadow. Its form is obtainable at t_L = 0.90 free from the influence of summating "cone" contributions, because then almost no overlapping occurs. Analysis shows that when overlapping does occur a certain number of rod units are inhibited by concurrent cone excitation, and that the mean contribution of elements of neural action from each of the non-inhibited units is also reduced to an extent depending on the degree of overlap. The isolated "rod" curve at t_L = 0.90 is quite accurately in the form of a probability integral. The data thus give a new experimental proof of the occurrence of two distinct but interlocking populations of visual effects, and experimentally justify the analytical procedures which have been used to separate them. 2. The changing form of the F - log I contour as a function of t_L, produced in man when the illuminated field is divided into parts by a shadow pattern, is normally found with the bird Taeniopygia castenotis (Gould), the zebra finch. The retina has elements of one general structural type (cones), and the F - log I contour is a simplex symmetrical probability integral. The eye of this bird has a large, complex, and darkly pigmented pecten, which casts a foliated shadow on the retina. The change in form of the F - log I curve occurs with t_L above 0,50, and at t_L = 0.90 is quite extreme. It is more pronounced than the one that is secured in the human data with the particular grid we have used, but there is no doubt that it could be mimicked completely by the use of other grids. The increase of flicker acuity due to the pecten shadow is considerable, when the dark spaces are brief relative to the light. The evidence thus confirms the suggestion (Menner) drawn from comparative natural history that the visual significance of the avian pecten might be to increase the sensory effect of small moving images. It is theoretically important that (as in the human experiment) this may be brought about by an actual decrease of effective retinal area illuminated. It is also significant theoretically that despite the presence of shadows of pecten or of grid, and of the sensory influences thus introduced, the probability integral formulation remains effective.     

Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome

ObjectiveIt has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.MethodsEighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP_SB) and abdominal muscle paralysis group (BIPAP_AP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH₂O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO₂ of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment.ResultsFor the comparable ventilator setting, as compared with BIPAP_SB group, the BIPAP_AP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP_AP group (22.5±2.0 vs. 25.2±2.1).ConclusionAbdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.     

INTERMITTENT STIMULATION BY LIGHT : III. THE RELATION BETWEEN INTENSITY AND CRITICAL FUSION FREQUENCY FOR DIFFERENT RETINAL LOCATIONS

When measurements of the critical fusion frequency for white light over a large range of intensities are made with the rod-free area of the fovea, the relation between critical frequency and log I is given by a single sigmoid curve, the middle portion of which approximates a straight line whose slope is 11.0. This single relation must be a function of the foveal cones. When the measurements are made with a retinal area placed 5° from the fovea, and therefore containing both rods and cones, the relation between critical frequency and log I shows two clearly separated sections. At the lower intensities the relation is sigmoid and reaches an upper level at about 10 cycles per second, which is maintained for 1.25 log units, and is followed by another sigmoid relationship at the higher intensities similar to the one given by the rod-free area alone. These two parts of the data are obviously separate functions of the rods at low intensities and of the cones at high intensities. This is further borne out by similar measurements made with retinal areas 15° and 20° from the fovea where the ratio of rods to cones is anatomically greater than at 5°. The two sections of the data come out farther apart on the intensity scale, the rod portion being at lower intensities and the cone portion at higher intensities than at 5°. The general form of the relation between critical frequency and intensity is therefore determined by the relative predominance of the cones and the rods in the retinal area used for the measurements.     

THEORY AND MEASUREMENT OF VISUAL MECHANISMS : I. A VISUAL DISCRIMINOMETER. II. THRESHOLD STIMULUS INTENSITY AND RETINAL POSITION

Monocular threshold stimulus intensities (ΔI_o, photons) were measured along the 0–180° meridian of human retinae for three observers. The test image was small (= 0.08°) and of short duration (= 0.20 second). ΔI_o was found to decrease as the angular distance from the fovea was increased. Actual counts of the number of retinal elements per mm.² along the 0–180° meridian (Østerberg) were compared with the obtained results. No direct correlation was found to exist between visual sensitivity and the number of retinal elements. Binocular threshold stimuli were also measured along the same meridian. The form of the function relating binocular visual sensitivity and retinal position was discovered to be essentially similar to that for monocular sensitivity, but is more symmetrical about the center of the fovea. The magnitude of the binocular measurement is in each case smaller than that of the monocular threshold stimulus intensity for the more sensitive eye. The ratio is statistically equal to 1.4 (a fact which suggests Piper''s rule). These results are shown to be consistent with the hypothesis that the process critical for the eventuation of the threshold response is localized in the central nervous system. They are not consistent with the view that the quantitative properties of visual data are directly determined by properties of the peripheral retina.     

Resveratrol Attenuates the Na+-Dependent Intracellular Ca2+ Overload by Inhibiting H2O2-Induced Increase in Late Sodium Current in Ventricular Myocytes

Background/Aims

Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H₂O₂)-induced increase in late sodium current (I _Na.L) which augmented the reverse Na⁺-Ca²⁺ exchanger current (I _NCX), and the diastolic intracellular Ca²⁺ concentration in ventricular myocytes.

Methods

I _Na.L, I _NCX, L-type Ca²⁺ current (I _Ca.L) and intracellular Ca²⁺ properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix), respectively, in rabbit ventricular myocytes.

Results

Resveratrol (10, 20, 40 and 80 µM) decreased I _Na.L in myocytes both in the absence and presence of H₂O₂ (300 µM) in a concentration dependent manner. Ranolazine (3–9 µM) and tetrodotoxin (TTX, 4 µM), I _Na.L inhibitors, decreased I _Na.L in cardiomyocytes in the presence of 300 µM H₂O₂. H₂O₂ (300 µM) increased the reverse I _NCX and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H₂O₂ of the diastolic intracellular Ca²⁺ fura-2 fluorescence intensity (FFI), fura-fluorescence intensity change (△FFI), maximal velocity of intracellular Ca²⁺ transient rise and decay. As expected, 2 µM TTX had no effect on I _Ca.L.

Conclusion

Resveratrol protects the cardiomyocytes by inhibiting the H₂O₂-induced augmentation of I _Na.L.and may contribute to the reduction of ischemia-induced lethal arrhythmias.     

CRITICAL INTENSITY AND FLASH DURATION FOR RESPONSE TO FLICKER: WITH ANAX LARVAE

Determinations of the flicker response curve (F – log I_m) with larvae of Anax junius (dragonfly) for various ratios t_L/t_D of light time to dark time in a flash cycle provide relations between t_L/t_D and the parameters of the probability integral fundamentally describing the F – log I function, including the variability of I. These relations are quantitatively of the same form as those found for this function in the sunfish, and are therefore non-specific. Their meaning for the theory of reaction to visual flicker is discussed. The asymmetry of the Anax curve, resulting from mechanical conditions affecting the reception of light by the arthropod eye, is (as predicted) reduced by relative lengthening of the fractional light time in a cycle.     

ON THE VARIABILITY OF CRITICAL ILLUMINATION FOR FLICKER FUSION AND INTENSITY DISCRIMINATION

From the data of experiments with bees in which threshold response is employed as a means of recognizing visual discrimination between stripes of equal width alternately illuminated by intensities I ₁ and I ₂, it is shown that the detectable increment of intensity ΔI, where ΔI = I ₂ - I ₁, is directly proportional to σ_I2 (I ₁ being fixed). From tests of visual acuity, where I ₁ = 0 and the width of the stripes is varied, σ_I2 = kI ₂ + const.; here I ₂ = ΔI, and ΔI/I ₂ = 1. When the visual excitability of the bee is changed by dark adaptation, λI ≡ kΔI (= k'' σ_ΔI) = k'''' I + const. For the measurements of critical illumination at threshold response to flicker, σ_I2 (= σ_ΔI) = k I ₂ = k'' ΔI + const. The data for critical illumination producing threshold response to flicker in the sun-fish Lepomis show for the rods σ_I2 = K I ₂ for the cones σ_I2 = K''(I ₂ + const.). The data thus indicate that in all these experiments essentially the same visual function is being examined, and that the recognition of the production of a difference in effect by alternately illuminated stripes takes place in such a way that d (ΔI)/d (σ_I2) = const., and that ΔI is directly proportional to I (or "I ₂," depending on the nature of the experiment). It is pointed out that the curve for each of the cases considered can be gotten equally well if mean I or σ_I is plotted as a function of the independent variable involved in the experiment. Certain consequences of these and related facts are important for the treatment of the general problem of intensity discrimination.