Multiscale modeling of mechanotransduction in the utricle.

We review recent progress in using numerical models to relate utricular hair bundle and otoconial membrane (OM) structure to the functional requirements imposed by natural behavior in turtles. The head movements section reviews the evolution of experimental attempts to understand vestibular system function with emphasis on turtles, including data showing that accelerations occurring during natural head movements achieve higher magnitudes and frequencies than previously assumed. The structure section reviews quantitative anatomical data documenting topographical variation in the structures underlying macromechanical and micromechanical responses of the turtle utricle to head movement: hair bundles, OM, and bundle-OM coupling. The macromechanics section reviews macromechanical models that incorporate realistic anatomical and mechanical parameters and reveal that the system is significantly underdamped, contrary to previous assumptions. The micromechanics: hair bundle motion and met currents section reviews work based on micromechanical models, which demonstrates that topographical variation in the structure of hair bundles and OM, and their mode of coupling, result in regional specializations for signaling of low frequency (or static) head position and high frequency head accelerations. We conclude that computational models based on empirical data are especially promising for investigating mechanotransduction in this challenging sensorimotor system.

Utricular afferents: morphology of peripheral terminals.

The utricle provides critical information about spatiotemporal properties of head movement. It comprises multiple subdivisions whose functional roles are poorly understood. We previously identified four subdivisions in turtle utricle, based on hair bundle structure and mechanics, otoconial membrane structure and hair bundle coupling, and immunoreactivity to calcium-binding proteins. Here we ask whether these macular subdivisions are innervated by distinctive populations of afferents to help us understand the role each subdivision plays in signaling head movements. We quantified the morphology of 173 afferents and identified six afferent classes, which differ in structure and macular locus. Calyceal and dimorphic afferents innervate one striolar band. Bouton afferents innervate a second striolar band; they have elongated terminals and the thickest processes and axons of all bouton units. Bouton afferents in lateral (LES) and medial (MES) extrastriolae have small-diameter axons but differ in collecting area, bouton number, and hair cell contacts (LES >> MES). A fourth, distinctive population of bouton afferents supplies the juxtastriola. These results, combined with our earlier findings on utricular hair cells and the otoconial membrane, suggest the hypotheses that MES and calyceal afferents encode head movement direction with high spatial resolution and that MES afferents are well suited to signal three-dimensional head orientation and striolar afferents to signal head movement onset.

Steady-state stiffness of utricular hair cells depends on macular location and hair bundle structure.

Spatial and temporal properties of head movement are encoded by vestibular hair cells in the inner ear. One of the most striking features of these receptors is the orderly structural variation in their mechanoreceptive hair bundles, but the functional significance of this diversity is poorly understood. We tested the hypothesis that hair bundle structure is a significant contributor to hair bundle mechanics by comparing structure and steady-state stiffness of 73 hair bundles at varying locations on the utricular macula. Our first major finding is that stiffness of utricular hair bundles varies systematically with macular locus. Stiffness values are highest in the striola, near the line of hair bundle polarity reversal, and decline exponentially toward the medial extrastriola. Striolar bundles are significantly more stiff than those in medial (median: 8.9 µN/m) and lateral (2.0 µN/m) extrastriolae. Within the striola, bundle stiffness is greatest in zone 2 (106.4 µN/m), a band of type II hair cells, and significantly less in zone 3 (30.6 µN/m), which contains the only type I hair cells in the macula. Bathing bundles in media that break interciliary links produced changes in bundle stiffness with predictable time course and magnitude, suggesting that links were intact in our standard media and contributed normally to bundle stiffness during measurements. Our second major finding is that bundle structure is a significant predictor of steady-state stiffness: the heights of kinocilia and the tallest stereocilia are the most important determinants of bundle stiffness. Our results suggest 1) a functional interpretation of bundle height variability in vertebrate vestibular organs, 2) a role for the striola in detecting onset of head movement, and 3) the hypothesis that differences in bundle stiffness contribute to diversity in afferent response dynamics.

Autocorrelation analysis of hair bundle structure in the utricle.

The ability of hair bundles to signal head movements and sounds depends significantly on their structure, but a quantitative picture of bundle structure has proved elusive. The problem is acute for vestibular organs because their hair bundles exhibit complex morphologies that vary with endorgan, hair cell type, and epithelial locus. Here we use autocorrelation analysis to quantify stereociliary arrays (the number, spacing, and distribution of stereocilia) on hair cells of the turtle utricle. Our first goal was to characterize zonal variation across the macula, from medial extrastriola, through striola, to lateral extrastriola. This is important because it may help explain zonal variation in response dynamics of utricular hair cells and afferents. We also use known differences in type I and II bundles to estimate array characteristics of these two hair cell types. Our second goal was to quantify variation in array orientation at single macular loci and use this to estimate directional tuning in utricular afferents. Our major findings are that, of the features measured, array width is the most distinctive feature of striolar bundles, and within the striola there are significant, negatively correlated gradients in stereocilia number and spacing that parallel gradients in bundle heights. Together with previous results on stereocilia number and bundle heights, our results support the hypothesis that striolar hair cells are specialized to signal high-frequency/acceleration head movements. Finally, there is substantial variation in bundle orientation at single macular loci that may help explain why utricular afferents respond to stimuli orthogonal to their preferred directions.

Dynamic properties of retino-geniculate synapses in the cat.

Simultaneous recordings from relay cells in the lateral geniculate nucleus (LGN) and their retinal afferents were used to examine the rules governing the transmission of spikes across the retino-geniculate synapse. Retinal spikes that terminate short retinal interspike intervals are much more likely to be transmitted across the synapse than spikes terminating longer intervals. This facilitation can be observed for interspike intervals as long as 50 ms when retinal firing rates are low, but the range of effective intervals decreases exponentially as retinal firing rate increases. Contribution, the fraction of LGN spikes triggered by an individual retinal afferent, is typically much higher during visual stimulation than during maintained activity, and these differences are unrelated to presynaptic or postsynaptic firing rate. It is suggested that this effect is a manifestation of increased synchronization of spikes among retinal afferents to the geniculate cell during structured visual stimulation, and that this synchronization offers a means of enhancing signal-to-noise ratio at the retino-geniculate synapse. Cross-correlograms between geniculate burst spikes and retinal afferents often contain two distinct peaks; a short latency peak that results from direct coupling between burst spikes and retinal input spikes, and a longer latency peak that represents indirect coupling in which retinal spikes trigger the calcium spike underlying the burst. Direct coupling is most likely to occur for the later spikes in the burst, and is present regardless of whether the calcium spike underlying the burst is triggered by the same or a different retinal afferent. These results further illuminate the relationship between tonic and burst modes of retino-geniculate transmission and indicate that bursts in LGN relay cells can be viewed as a mechanism of signal amplification, producing signals whose timing is potentially related to the temporal structure of a stimulus, independent of presynaptic and postsynaptic firing rate. This mechanism also appears to capitalize on the synchronization that is present among parallel retinal afferents to a geniculate cell.

Spatial and temporal properties of cat horizontal cells after prolonged dark adaptation.

We studied the change of spatial and temporal response properties for cat horizontal (H-) cells during prolonged dark adaptation. H-cell responses were recorded intracellularly in the optically intact, in vivo eye. Spatial and temporal properties were first measured for light-adapted H-cells, followed by a period of dark adaptation, after which the same measurements were repeated. During dark adaptation threshold sensitivity was measured at regular intervals. Stable, long lasting recordings allowed us to measure changes of sensitivity and receptive field characteristics for adaptation periods up to 45 min. Although cat H-cells showed no signs of dark suppression or light sensitization, they remained insensitive in the scotopic range, even after prolonged dark adaptation. Absolute thresholds were in the low mesopic range. The sensitization was brought about by a shift from cone to rod input, and by substantial increases of both spatial and temporal integration upon dark adaptation. The length constant in the light-adapted state was on average about 4 deg. After dark adaptation it was up to a factor of three larger, with a median ratio of 1.85. Response delays, latencies and durations for (equal amplitude) threshold flash responses substantially increased during dark adaptation.

Gain control and hyperpolarization level in cat horizontal cells as a function of light and dark adaptation.

First a model is presented that accurately summarizes the dynamic properties of cat horizontal (H-) cells under photopic conditions as measured in our previous work. The model predicts that asymmetries in response to dark as compared to light flashes are flash-duration dependent. This somewhat surprising prediction is tested and confirmed in intracellular recordings from the optically intact in vivo eye of the cat (Experiment 1). The model implies that the gain of H-cells should be related rather directly to the sustained (baseline) membrane potential. We performed three additional experiments to test this idea. Experiment 2 concerns response vs intensity (R-I-) curves for various flash-diameters and background-sizes with background luminance varying over a 4 log unit range. Results support the assumption of a rather strict coupling between flash sensitivity (gain) and the sustained level of hyperpolarization. In Experiment 3 we investigate this relation for both dark and light flashes given on each of four background light levels. The results suggest that there are fixed minimum and maximum hyperpolarization levels, and that the baseline hyperpolarization for a given illumination thus also sets the available range for dark and light flash-responses. The question then arises whether, or how this changes during dark adaptation, when the rod contribution to H-cell responses gradually increases. The fourth experiment therefore studies the relationship between gain and hyperpolarization level during prolonged dark-adaptation. The results show that the rod contribution increases the polarization range of H-cells, but that the gain and polarization level nevertheless remain directly coupled. H-cell models relying on a close coupling between polarization level and gain thus remain attractive options.

Horizontal cell sensitivity in the cat retina during prolonged dark adaptation.

The effects of dark adaptation on the response properties of ganglion cells have been documented extensively in the cat retina. To pinpoint the different retinal mechanisms that underlie these effects, we studied the response characteristics of cat horizontal (H) cells during prolonged dark adaptation. H-cell responses were recorded intracellularly in the optically intact, in vivo eye. To disentangle rod and cone contributions, sensitivity changes during dark adaptation were tracked with white light and with monochromatic lights that favored either rod or cone excitation. Stable, long-lasting recordings allowed us to measure changes of sensitivity for adaptation periods up to 45 min. Thresholds for white light and 503-nm monochromatic light decreased steadily and in parallel. The maximum increase of sensitivity, after extinguishing a photopic adaptation light, was 1.8 log units only, reached after about 35 min. Sensitivity for 581-nm lights also increased steadily, but at a shallower slope. The steady increase of sensitivity was concomitant with a linear shift in resting membrane potential and with an increase in relative rod contribution to the threshold responses. Even though small-amplitude responses were rod dominated after prolonged dark adaptation, sensitivity to rod signals remained relatively low, compared to sensitivity of cone responses or to the absolute sensitivity of ganglion cells. This suggests that the cone-H-cell pathway plays no role in the dark-adapted cat retina.

Linear and nonlinear contributions to step responses in cat retinal ganglion cells.

We measured excitatory and inhibitory step responses of cat retinal ganglion cells to square wave contrast reversal of stationary sinusoidal gratings. In most Y-cells the initial increase in firing rate (early peak) of the excitatory responses was followed by a distinct second increase in firing rate (late peak). Analysis of the spatial frequency and spatial phase dependence of the two peaks indicated that the early peak appears to be produced by the spatially linear center mechanism, while the late peak appears to be produced by the rectifying subunits described by Hochstein and Shapley (1976) Journal of Physiology, London, 262, 237-264, 265-284. These results indicate that the presence of two peaks in ganglion cell step responses is the result of two excitatory inputs with different time courses, and that inhibitory inputs are not required to explain the appearance of these responses.

Spatio-temporal receptive-field structure of phasic W cells in the cat retina.

The spatio-temporal receptive-field structure of 54 phasic W cells in cat retinas has been examined using the reverse-correlation method of Jones and Palmer (1987). Within this sample, 12 cells had on-center, 16 off-center, and 26 on-off receptive fields. Three of the on-center and seven of the on-off cells were directionally selective. Forty percent of the cells in this sample had local receptive fields consisting of two or more distinct subregions. However, no correlation was observed between the number of subregions in the local receptive field and other response properties such as center sign or direction selectivity. In all cases, individual subregions, including those in on-off cells, appear to be produced by a half-wave rectification of the input signal. For 76% of the cells, these local receptive fields were contained within large suppressive fields which could be seen to extend for at least 10 deg in all directions with no apparent spatial structure. The mechanism producing the suppressive field also appears to involve a rectification of the input signal, and has a relatively high spatial resolution. Furthermore, the suppressive field itself is only responsive to moving or flickering stimuli; large, stationary gratings have no effect on the output of the local receptive-field mechanism. Thus, the overall receptive-field organization of these cells is particularly well suited for detecting local motion. The remaining 24% of cells in the sample lacked suppressive fields, and consequently responded well to large moving stimuli, but these cells were otherwise similar in their receptive-field properties to cells with suppressive fields. The significance of these properties is discussed in the context of the projections of phasic W cells to the superior colliculus and accessory optic system.

Spatial receptive-field structure of cat retinal W cells.

We have used frequency-domain methods to characterize the spatial receptive-field structure of cat retinal W cells. For most ON- and OFF-center tonic and phasic W cells, measurements of responsivity to drifting gratings at various spatial frequencies could be adequately described by a difference-of-Gaussians (DOG) function, consistent with the presence of center and surround mechanisms that are approximately Gaussian in shape and whose signals are combined additively. Estimates of the responsivity of the center mechanisms of tonic and phasic W cells were similar, but both were significantly lower than the corresponding values for X or Y cells. The width of the center mechanisms of tonic W cells, phasic W cells, and Y cells did not differ significantly from each other, but all were significantly larger than the width of X-cell centers. Surround parameters did not vary significantly among the four groups of ganglion cells. Measurements of contrast gain in both tonic and phasic W cells gave values that were significantly lower than in X or Y cells. Virtually all of the phasic W cells in our sample displayed evidence of spatial non-linearities in their receptive fields, in the form of either d.c. responses to drifting sine-wave gratings or second harmonic responses to counterphased gratings. The spatial resolution of the mechanism underlying these nonlinearities was typically higher than that of the center mechanism of these cells. Most tonic W cells exhibited linear spatial summation, although a subset gave strong second harmonic responses to counterphased gratings. Spatial-responsivity measurements for most ON-OFF and directionally selective W cells were not adequately described by DOG functions. These cells did, however, show evidence of spatial nonlinearities similar to those seen in phasic W cells. Suppressed-by-contrast cells gave both modulated and unmodulated responses to drifting gratings which both appeared to involved rectification, but which differed from each other in both spatial resolution and contrast gain. These data confirm earlier reports that the receptive fields of tonic and most ON- or OFF-center phasic W cells appear to include classical center and surround mechanisms. However, the receptive fields of some phasic cells, as well as ON-OFF and directionally selective W cells may have quite different structures. Our results also suggest that phasic, ON-OFF, directionally selective, suppressed-by-contrast, and a subset of tonic W cells may all receive nonlinear inputs with characteristics similar to those described in the receptive fields of retinal Y cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Restenosis after directional coronary atherectomy.

OBJECTIVES: This study evaluates the incidence of restenosis after successful directional coronary atherectomy and identifies risk factors for restenosis. BACKGROUND: Directional coronary atherectomy has been shown to be a safe and effective treatment of obstructive coronary artery disease; however, information regarding restenosis is limited. METHODS: Between October 1986 and December 1989, 289 patients with 332 lesions were successfully treated with directional coronary atherectomy and followed up prospectively. Clinical follow-up information was available for 98% and angiographic follow-up information was obtained for 82% at approximately 6 months, or earlier if symptoms recurred. Angiograms were quantitatively analyzed. Restenosis was defined as greater than 50% stenosis at the site of intervention. RESULTS: Seventy-four percent of patients were either asymptomatic or clinically improved after the procedure. Thirty-two percent were subsequently treated by coronary artery bypass surgery (14%), percutaneous transluminal coronary angioplasty (4%) or repeat atherectomy (13%). Angiographic evidence of restenosis was observed in 42%. The restenosis rate in native coronary arteries was 31% for primary lesions and 28% and 49%, respectively, for lesions treated with one or two previous angioplasty procedures. The restenosis rate for saphenous vein grafts was 53% for primary lesions and 58% and 82%, respectively, for lesions treated with one or two previous angioplasty procedures. The median interval to angiographically documented restenosis was 133 days. A higher restenosis rate was associated with a saphenous vein graft, hypertension, a longer lesion (greater than or equal to 10 mm), a smaller vessel diameter (less than 3 mm), a noncalcified lesion and use of a smaller (6F) device. CONCLUSIONS: Restenosis remains a limitation of directional coronary atherectomy. A subset of patients with larger vessels, shorter lesions or lesions treated with a larger (7F) device may have a more favorable outcome.

Effects of selective pressure block of Y-type optic nerve fibers on the receptive-field properties of neurons in the striate cortex of the cat.

In an aseptic operation under surgical anesthesia, one optic nerve of a cat was exposed and subjected to pressure by means of a special cuff. The conduction of impulses through the pressurized region was monitored by means of electrodes which remained in the animal after the operation. The pressure was adjusted to selectively eliminate conduction in the largest fibers (Y-type) but not in the medium-size fibers (X-type). The conduction block is probably due to a demyelination and remains complete for about 3 weeks. Within 2 weeks after the pressure-block operation, recordings were made from single neurons in the striate cortex (area 17, area V1) of the cat anesthetized with N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate. Neurons were activated visually via the normal eye and via the eye with the pressure-blocked optic nerve ("Y-blocked eye"). Several properties of the receptive fields of single neurons in area 17 such as S (simple) or C (complex) type of receptive-field organization, size of discharge fields, orientation tuning, direction-selectivity indices, and end-zone inhibition appear to be unaffected by removal of the Y-type input. On the other hand, the peak discharge rates to stimuli presented via the Y-blocked eye were significantly lower than those to stimuli presented via the normal eye. As a result, the eye-dominance histogram was shifted markedly towards the normal eye implying that there is a significant excitatory Y-type input to area 17. In a substantial proportion of area 17 neurons, this input converges onto the cells which receive also non-Y-type inputs. In one respect, velocity sensitivity, removal of the Y input had a weak but significant effect. In particular, C (but not S) cells when activated via the normal eye responded optimally at slightly higher stimulus velocities than when activated via the Y-blocked eye. These results suggest that the Y input makes a distinct contribution to velocity sensitivity in area 17 but only in C-type neurons. Overall, our results lead us to the conclusion that the Y-type input to the striate cortex of the cat makes a significant contribution to the strength of the excitatory response of many neurons in this area. However, the contributions of Y-type input to the mechanism(s) underlying many of the receptive-field properties of neurons in this area are not distinguishable from those of the non-Y-type visual inputs.

Disruption of developmental timing in the albino rat retina.

We have examined the spatial and temporal gradients of two developmental processes in albino and pigmented rats: outer plexiform layer (OPL) development, and rate of cell production. The OPL first appears as a thin, discontinuous break in the cytoblast layer that is frequently interrupted by the profiles of migrating neuro- and glioblasts. In both strains, this occurs in an area temporal to the optic disc that corresponds to the eventual site of peak ganglion cell density, but is not located along the line of nasotemporal division. The OPL is first evident at P5 in pigmented animals, but its appearance in albino animals is delayed approximately 30 hours, and its development appears to follow a flatter spatial gradient than in pigmented animals. In pigmented animals OPL formation is complete over most of the retina by P10, but in albino animals at this age it is yet to be completely formed at any retinal location. Reductions in mitotic activity are also first evident in temporal retina, but unlike OPL development, appear to follow the same temporal-spatial gradient in both strains. Reductions in temporal retina are obvious by P4, and mitotic activity has ceased altogether in midtemporal retina by P6 and throughout most remaining retinal regions by P8. Thus, the initial reduction of mitotic activity precedes the onset of OPL formation in both strains, but OPL development lags behind the reduction of mitotic activity to a greater extent in albino than in pigmented animals. Some aspects of differentiation within the inner nuclear layer (INL) were also examined. Just prior to the time of the onset of OPL formation, three distinct sublaminae are apparent in the INL. Cells in the innermost sublamina appear to be in an early stage of differentiation. Cells in the middle sublamina appear to be postmigratory, but have not yet begun to differentiate. Cells in the outermost sublamina have the appearance of migrating neuroblasts. At least some of these outer cells appear to migrate across the developing OPL to the outer nuclear layer, since the outermost sublamina becomes thinner and eventually disappears at the same time that the OPL becomes a continuous, uninterrupted plexiform layer. Cells of the middle sublamina apparently begin differentiation at about the time that this migration is complete. Although this sequence is the same in both albino and pigmented strains, its onset is delayed in albino animals by the same amount as the onset of OPL formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of lesion characteristics on outcome of directional coronary atherectomy.

Directional coronary atherectomy, a new transluminal procedure for treatment of obstructive lesions in coronary arteries by excision and removal of tissue, was performed on 447 lesions in 382 procedures. Successful outcome, defined as a reduction of stenosis by greater than or equal to 20% with a less than 50% residual stenosis, was achieved in 89.5% of lesions and mean stenosis was reduced from 75.9 +/- 13.3% to 14.5 +/- 22.1% (p less than 0.001). Complications included vessel occlusion during the procedure, 2.4%; vessel occlusion after the procedure, 1.3%; new lesion, 0.5%; nonobstructive guiding catheter-induced dissection, 0.3%; perforation, 0.8%; distal embolization, 2.1%; Q wave myocardial infarction, 0.8% and non-Q wave myocardial infarction, 4.2%. Twelve patients (3.1%) required coronary artery bypass surgery for these complications. The atherectomy success rate was greater than 80% and the combined atherectomy and angioplasty success rate was greater than 90% for complex morphologic features such as eccentric lesions, lengthy lesions, lesions with abnormal contour, angulated lesions, ostial lesions and lesions with branch involvement. In the presence of calcific deposition, atherectomy success rate was 52% for primary lesions and 83% for restenosed lesions. Among angiographically complex lesions, calcium was the predictor for failed atherectomy (p less than 0.0001). In summary, directional coronary atherectomy is safe and effective for treatment of obstructive lesions in coronary arteries in selected cases. In particular, it achieves a high success rate in lesions with complex morphologic characteristics, such as eccentricity, abnormal contour and ostial involvement.

Comparison of dissection rates and angiographic results following directional coronary atherectomy and coronary angioplasty.

Directional coronary atherectomy is a new percutaneous transluminal technique for treating occlusive coronary artery disease. In this study, angiographic results (i.e., residual stenosis and angiographic evidence of postprocedure dissection) after directional coronary atherectomy and balloon angioplasty were compared. The atherectomy group consisted of 91 lesions in 83 consecutive patients who underwent either left anterior descending artery or right coronary artery atherectomy. The angioplasty group consisted of 91 lesions in 84 patients that were matched with the atherectomy lesions with respect to vessel and whether the lesion was a restenosis lesion. The mean preprocedure diameter stenosis was 76% in both groups as measured quantitatively with electronic calipers. After the procedure, the mean residual diameter stenosis of the atherectomy lesions was 13 +/- 17%, whereas for the angioplasty lesions it was 31 +/- 18% (p less than 0.001). Success rates in both groups were similar (94.5 and 93.4%, respectively). The incidence of postprocedure dissection was 11% in the atherectomy group and 37% in the angioplasty group (p less than 0.0001). Directional coronary atherectomy results in significantly improved postprocedure angiographic appearances due to significantly less severe residual stenosis and lower incidence of dissection.

Reduced conduction velocity of retinal Y-cell axons following early partial removal of their synaptic targets.

Following unilateral visual cortex ablation in neonatal kittens, the extraretinal conduction velocities of retinal Y-cell axons projecting to the lesioned hemisphere were measured and compared to the velocities of Y-cell axons projecting to the intact hemisphere. The extraretinal velocities of Y-cells projecting to the lesioned hemisphere were 16-28% lower than the velocities of Y-cells projecting to the intact hemisphere. This effect was seen in axons originating in both the ipsilateral and contralateral retinae. These data are consistent with the hypothesis that one factor regulating axon size is the amount of synaptic territory which is available to the cell. When the velocities of the unmyelinated intraretinal portions of Y-axons were examined in experimental animals, no significant differences could be detected between axons projecting to the lesioned hemisphere and those projecting to the intact hemisphere.

Evidence for degeneration of retinal W cells following early visual cortical removal in cats.

Size and distribution of ganglion cells surviving unilateral visual cortical removal at 5-7 days of age were examined in domestic cats. Such lesions were expected to result in a substantial loss of X cells in ipsilateral temporal and contralateral nasal retina, leaving ipsilateral nasal and contralateral temporal retina to serve as intact controls. A computer model of normal retinal ganglion cell topography was used to make qualitative predictions of the distribution of surviving ganglion cells. Contrary to expectations, a visual streak was no more prominent in the distribution of surviving cells than in the distribution of the normal ganglion cell population. The magnitude of ganglion cell loss, furthermore, was at least twice as great in nasal retina as in temporal retina. In nasal retina, the cell loss extended well into the small-medium size range, while in temporal retina, cell loss was restricted to the large-medium size range. Taken together, the differential magnitude of cell loss in nasal and temporal retina and the greater loss of small-medium cells in nasal retina cannot be explained by the exclusive degeneration of X cells and suggest that many of the degenerated ganglion cells were medium-sized W or gamma cells. These cells, therefore, share the susceptibility of retinal X cells to early cortical ablation. Surviving gamma cells in both nasal and temporal retina appeared to increase in soma size which may explain why their decreased numbers were not detected in previous physiological studies. Alpha cells, at least in nasal retina, decreased in some size.

Early and late survival after coronary-artery surgery.

Between 1970 and 1985, 1801 patients underwent coronary-artery surgery without associated valvular surgery. Eighty-four per cent of patients were male and the mean (+/- SD) age was 55.7 +/- 8.3 years. Of the patients, 18.7% were from the Coronary Care Unit and 6.5% had diabetes. The hospital mortality rate for the whole group was 3.5%. Patients from the Coronary Care Unit had the highest (8.9%) hospital mortality rate compared with those patients who were not from the Coronary Care Unit (2.1%; P less than 0.001). Other factors which increased the hospital mortality rate significantly were the number of diseased vessels (P less than 0.01), the degree of left main coronary-artery stenosis (P less than 0.001), an earlier year of surgery (P less than 0.01) and female sex (P less than 0.01). After these were taken into account, no other factors (for example, age, preoperative infarction, presence of left-ventricular aneurysm, left-ventricular end-diastolic pressure, diabetes, use of mammary-arterial grafts or the need for endarterectomy) affected the mortality rate. Patients were followed-up for a mean (+/- SD) of 4.4 +/- 2.8 years. The five-year survival rate for all patients was 88% and the 10-year survival rate was 65%. Cox regression analysis showed that the significant indicators of decreased long-term survival were undergoing operation directly from the Coronary Care Unit (P less than 0.001), left main coronary-artery stenosis (P less than 0.01), the number of grafted vessels (P less than 0.01), concomitant surgery for aneurysm (P less than 0.001), year of surgery (P less than 0.01). Seventy-nine per cent of patients were free of angina pectoris at five years after operation. The year of surgery (P less than 0.001) and preoperative myocardial infarction (P less than 0.05) were the best predictors of recurrent angina. In the long term, recurrent angina remains a problem, although this may change with the increased use of mammary-arterial grafts.

Effect of rapid mobilization on ejection fractions and ventricular volumes after acute myocardial infarction.

Despite the current practice of early mobilization and early hospital discharge after uncomplicated acute myocardial infarction (AMI), physicians are reluctant to permit normal physical and social activity for several weeks after the AMI "to allow the heart to heal." This study tested whether it was possible to identify a low risk group of patients on day 3 after AMI, and whether vigorous early mobilization from days 4 through 7 affected left ventricular function and volumes (studied by gated blood pool scan on days 4 and 14). There was 1 death in 3 months in 45 patients with uncomplicated AMI suitable for randomization to activity (group A) compared with 11 deaths in 55 patients unsuitable for rapid early mobilization (group B) (p less than 0.01). Early vigorous mobilization in 24 of the group A patients compared with sedentary care in 20 did not affect change in ejection fraction, end-diastolic volume, end systolic-volume, stroke volume, heart rate or cardiac output between days 4 and 14. A very low risk group suitable for early vigorous mobilization can be defined on day 3 after AMI; further, vigorous early mobilization does not affect left ventricular function or volumes. Early return to physical, social and occupational activity after uncomplicated AMI should result in marked reduction in direct and indirect costs of AMI.