Effect of ligation of patent ductus arteriosus on left ventricular performance and its determinants in premature neonates.

OBJECTIVES: The purpose of this study was to determine in preterm newborn infants the effects of ductal ligation on ventricular performance and its determinants: preload, afterload and contractility. BACKGROUND: Neonatal ventricular performance is highly sensitive to afterload. Therefore, the increase in systemic vascular resistance associated with ligation of a patent ductus arteriosus might worsen ventricular performance in the preterm infant. METHODS: All 14 premature infants undergoing patent ductus arteriosus ligation in a 1-year period at our institution underwent echocardiography at three times: before, immediately after and 24 h after ligation. Indexes studied included ventricular performance (fractional area change), preload (left ventricular end-diastolic dimension), afterload (end-systolic wall stress) and contractility (the difference between the measured and predicted velocity of circumferential fiber shortening). Blood pressure was measured; systemic resistance was calculated. These data were compared with those of 14 preterm infants without patent ductus arteriosus. RESULTS: The infants with patent ductus arteriosus had higher values for ventricular performance (mean +/- SD fractional area change 60 +/- 9% vs. 52 +/- 11%, p < 0.05) and lower values for wall stress (22 +/- 6 vs. 44 +/- 17 g/cm2, p < 0.05) before ligation than did the control group. At 24 h after ligation, ventricular performance was not significantly changed (fractional area change 60 +/- 9% to 57 +/- 12%). There were significant increases in blood pressure and systemic vascular resistance but no changes in wall stress or contractility. CONCLUSIONS: Ventricular performance is higher in premature infants with than in those without patent ductus arteriosus because afterload is lower in the former group. Although ductal ligation increases blood pressure and systemic resistance, wall stress and ventricular performance are maintained. Our results suggest that the premature newborn maintains ventricular performance during stress, at least in part, by manipulating afterload.

Three-dimensional retinal image stability during visual tilt discrimination in the rabbit.

Rabbits trained to discriminate vertical vs. oblique striations are unable to discriminate angular differences of 5 degrees. In the present study the instabilities around the roll axis of the eyes were measured during visual discrimination. The results indicate that these instabilities are one of the causes of the rabbit's inability to discriminate angular differences of 5 degrees.

Visual discrimination of discontinuous figures in the rabbit.

Rabbits were trained to discriminate between vertical and horizontal striations. After the 90% correct level had been reached transfer to vertical and horizontal rows of dots was studied. It was found that performance depended on the distance between adjacent dots. With angular dot separations (measured from the centers) larger than 4.9 degrees, performance was below the 75% correct level. This result is discussed in relation to the size of the receptive fields of orientation-selective neurons in the binocular visual cortex.

Haemodynamic effects of respiratory alkalosis independent of changes in airway pressure in anaesthetized newborn dogs.

We have recently reported a decrease in cardiac output in newborn dogs during respiratory alkalosis which is independent of changes in airway pressure. The present study was designed to characterize the mechanism responsible for this reduction in cardiac output. Twelve newborn coonhounds were anaesthetized with pentobarbital, paralyzed with pancuronium and hyperventilated to an arterial carbon dioxide tension (PaCO2) of 20 torr. Subsequent changes in PaCO2 were achieved by altering the FiCO2. Measurements were made after 30 min at either 40 or 20 torr PaCO2. The sequence of PaCO2 levels was randomized. Compared to normocarbia, respiratory alkalosis resulted in significantly decreased cardiac output (279 +/- 16 to 222 +/- 10 ml/min per kg, mean +/- SEM, P less than 0.001), stroke volume (1.60 +/- 0.10 to 1.24 +/- 0.06 ml/kg; P less than 0.001), maximum left ventricular dP/dt (1629 +/- 108 to 1406 +/- 79 mmHg/s, P less than 0.01) and left ventricular end diastolic pressure (3.9 +/- 0.4 to 2.9 +/- 0.3 mmHg; P less than 0.001). The decrease in cardiac output during respiratory alkalosis is manifest through a decrease in stroke volume, which is due, at least in part, to the decrease in left ventricular end diastolic pressure. The decrease in maximum left ventricular dP/dt is likely a reflection of the decrease in preload, however, a change in myocardial contractility cannot be excluded. We speculate the decrease in filling pressure may be due to an increase in venous capacitance.

The contribution of the rewarded and the non-rewarded stimulus in visual discrimination learning in mice.

The relative contribution of the rewarded and non-rewarded stimulus in the learning of a visual discrimination task in various species is unclear. A number of different parameters have been suggested as influencing the importance of the one over the other, among them the type of reinforcement. Our results show that with both positive reinforcement (using water as reward after a correct choice, and no reinforcement after an incorrect choice) and negative reinforcement (electroshock punishment after an incorrect choice) mice use the position of the incorrect stimulus as a cue for the discrimination. Mice trained by positive reinforcement without the added negative reinforcement of blocking the door on which the incorrect stimulus is projected, do not learn a brightness discrimination task. This suggested that the added negative reinforcement of the closed door had a strong influence on the learning behaviour in our experiments.

Tilt discrimination in the mouse.

We tested the visual discrimination of mice in a two-choice discrimination box. After reaching criterion in a brightness discrimination the animals were trained on an orientation discrimination (vertical vs horizontal). Training was continued with the discrimination of vertical striations (S+) vs oblique ones (S-) of 10 different angles (80 to 15 degrees). The tilt discrimination for the last 5 days of training we found to be 30.5 (S.E.M. 3.2) degrees in albino and 19.9 (S.E.M. 0.7) degrees in pigmented mice. This is much higher than the 9.55 (S.E.M. 0.95) degrees found in pigmented rabbits but is comparable to the 17 degrees found in hooded rats by others.

Regional cerebral blood flow and cerebral metabolic rate of oxygen during hyperventilation in the newborn dog.

Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured during normocarbia and during both moderate and severe hypocarbia. Eighteen newborn mongrel dogs, 1 to 7 days of age, were given pancuronium and ventilated with 70% N2O and 30% O2. The respirator was adjusted to achieve a PaCO2 of 15 torr, all subsequent changes to 25 and 40 torr were made by adjusting the inspired concentration of CO2. The sequence of PaCO2 levels was randomized. CBF was measured by microsphere technique and CMRO2 calculated as arterial-sagittal sinus O2 content difference times hemispheric blood flow. All measurements were made after 30 min at each PaCO2. Total CBF was reduced at a PaCO2 of 25 torr (p less than 0.001), further reduction in PaCO2 to 15 torr resulted in a significant decrease in total CBF (p less than 0.01) compared to 25 torr CO2. All regional cerebral blood flows were reduced at a PaCO2 of 25 torr (p less than 0.001), and most regional CBFs had further significant decreases in flow at a PaCO2 of 15 torr. CMRO2 was 1.28 +/- 0.47 ml/100 g/min at a PaCO2 of 40 torr and fell to 1.09 +/- 0.34 (p less than 0.05) and to 1.04 +/- 0.28 (p less than 0.025) ml/100 g/min at PaCO2 values of 25 and 15 torr, respectively. Cardiac output was calculated to be 169 +/- 71 ml/kg/min at a PaCO2 of 40 torr and fell to 135 +/- 27 (p less than 0.025) and to 127 +/- 36 (p less than 0.005) ml/kg/min at PaCO2 values of 25 and 15 torr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of partial receptor cell loss on the electroretinogram of chimaeric mice.

A series of chimaeric mice were produced by aggregating morulae from rd/rd and normal (+/+) mice. In the retina of chimaeric mice, produced by aggregating morulae of these two genotypes, loss of rd/rd photoreceptor cells results in a patchy distribution of the surviving normal receptor cells. The number of remaining receptor cells vary between individual chimaeras. The inner retinal layers in the chimaeras, as well as in the two parental genotypes remain intact. Electroretinograms were recorded from 16 chimaeric mice, and various parameters were compared with the amount of visual cells present as estimated by the average thickness of the outer nuclear layer. The amplitudes of the a- and b-wave, showed a linear reduction with decreasing thickness of the outer nuclear layer thickness. However, threshold of the b-wave increased only when the thickness of the outer nuclear layer fell to about 25% of the normal thickness while the time-to-peak of the waves did not change appreciably among the chimaeric individuals. These results suggest that the changes in the electroretinogram of the chimaeric individuals are related to the amount of visual cells present in the retina.

Recovery from hypobaric hypoxia in the rabbit.

In rabbits, recovery was studied from hypobaric hypoxia elicited by decompression to 190 mm Hg. In the first experiment a pattern discrimination habit was used. A marked latency appeared after hypoxia, before the rabbits started to respond, but once started no difference was found compared to control circumstances. Repeating this procedure 48 h later resulted in a spontaneous decrease in latency, which remained significantly longer than without hypoxia. In the second experiment rabbits were on a time-restricted daily drinking schedule and the water drinking behaviour was registered. Due to the preceding hypoxia the rate of drinking was much lower compared with the control animals, as was the average total fluid intake. After 48 h the impact of hypoxia was much less. In the third experiment the influences of repeated periods of hypoxia upon the heart rate were studied. Rabbits showed a marked bradycardia during hypoxia which was less severe 48 h later. It was argued that studying recovery from hypoxia is potentially valuable to gain information about the effects of cerebral hypoxia and the autonomic responses that influence the final outcome of hypoxic stress in the intact rabbit.

Development and degeneration of retina in rds mutant mice: the electroretinogram.

In mice, homozygous for the retinal degeneration slow (rds) gene, the photoreceptor cells lack outer segment disc structures, contain low amounts of rhodopsin, and degenerate slowly, while the inner retinal layers remain intact. The electroretinogram (ERG) from 1-month-old mutant mice shows a lower than normal amplitude but the time-to-peak is normal. The ERGs from mutant mice of 2-3 months and 6-7 months of age show a further decline in response amplitude as the receptor cell population is depleted with progress of degeneration while the time-to-peak increases. The ERG is absent in 1-year-old mutant mice which have lost their receptor cells completely. The possible morphological correlations of the ERG and its components in the rds mutant mice are discussed.

Velocity-tuning of motion-sensitive and direction-selective cells in the rabbit striate cortex.

The receptive field characteristics of 268 striate cortical cells were classified in 10 Dutch-belted rabbits. From the 66 motion-sensitive and direction-selective units encountered, quantitative data describing the responses of 41 motion-sensitive, and 10 direction-selective cells to moving gratings were obtained. The results showed that all cells responded with increased spike discharges to increased velocities of the moving gratings up to a maximum, then they became less responsive to further increase of the velocities. The patterns of the response curves varied from cell to cell. When the 51 cells were taken as a whole, there were more cells responding to the velocities of 10-30 deg/sec than to higher or lower velocities. The total range over which these cells responded was 0.1-300 deg/sec. The preferred velocities for individual cells ranged from 1.5 to 150 deg/sec, showing a moderate concentration at the 6-40 deg/sec region. The extent of the effective velocities for individual cells formed a continuous distribution. No segregation into groups was seen in either of the two cell types studied or in all cells taken as a group. These data were compared with those reported for the rabbit retinal ganglion cells and the cells in the nucleus of the optic tract, as well as the cells in the cat visual system.

The dual effect of L-proline on spreading depression in the chicken retina.

Evidence was presented for a glutamate agonistic effect of L-proline which promotes K+-based spreading depressions (SD) in chick retinas at relatively high concentrations (5 mM), in addition to an antagonistic effect which inhibits glutamate-based SDs at lower (2 mM) concentrations. Together these effects explain the observed biphasic effect of L-proline on the incidence of SD in the retina.

The conduction velocity in retino geniculate afferent fibers in the rabbit.

We have recorded X- and Y-like cells in the rabbit lateral geniculated nucleus (LGN) and found a small but statistically significant difference between the latencies of the two cell types to stimulation of the chiasm. The relative frequency of recordable Y-cells was equal in pigmented and in albino rabbits. No relative increase in the recording probability of Y-cells versus X-cells was found with increasing eccentricity of the receptive field (RF) locations with respect to the visual streak in either breed.

The effect of exposure to continuous light on the ERG of syrian hamsters.

Reduction of ERG wave amplitude was found after exposure to continuous light in albino and pigmented hamsters. The reduction was strongest in albino hamsters. No effect on wave threshold was seen. Changes in time-to-peak were only found for the b-wave in exposed albino hamsters. Comparing these results with those previously found in rats under identical experimental conditions, we noted in hamsters: smaller reduction of amplitude, no increase of threshold and no increase of a-wave time-to-peak.

The development of the electroretinogram in normal and light-deprived rabbits.

1. The development of the ERG of the pigmented Dutch Belted rabbits is completed before the age of 5 weeks. 2. The a-wave amplitude attains the adult value by the age of 40 days. 3. The b-wave amplitude development is fastest before the age of 40 days but continues to increase afterwards probably due to increase of eye size. 4. Both a- and b-wave peak-latencies decrease with increasing age to the age of 40 days. 5. The b-wave seems to originate from two processes, one leading to a "slow b-wave" showing low threshold, long peak-latency and in adult animals no oscillatory potentials, which dominates the low stimulus intensity response. The other, a "fast b-wave" of higher threshold, shorter latency, and showing oscillatory potentials, dominates the high stimulus intensity response. 6. Light deprivation does not retard the early development of the ERG in rabbits.

Effect of azide on the ERG of the isolated mammalian retina.

Azide, which is known to affect the pigment epithelium strongly may be assumed to cause damage to the receptors, which are functionally connected to the pigment epithelium. To check this hypothesis the effect of azide on the ERG was investigated. An isolated retina preparation was used as in this preparation the P III component, which contains considerable receptor contribution, can be isolated. In 2 series of experiments the effects of azide on the P III and the complete ERG were investigated. Depending on the concentration azide was shown to abolish the b-wave, to cause delay and amplitude diminution of the P III and enhance a positive component in the off-effect. A number of plausible sites of origin of these azide effects on the ERG changes are discussed.

Renal response of the new-born dog to a saline load: the role of intrarenal blood flow distribution.

1. The renal response to an intravenous saline load was studied in thirty new-born mongrel dogs aged 1-30 days and in seven adult dogs.2. After the infusion of isotonic saline at a rate of 2.0 ml. min(-1) kg(-1) for 15 min and then at a rate of 0.5 ml. min(-1) kg(-1) for an additional 105 min, the puppies excreted a significantly smaller fraction of the infused sodium than did the adults (P < 0.01).3. Both puppies and adults increased their glomerular filtration rates after the saline load. However, adults excreted a larger fraction of their filtered sodium than did the puppies (P < 0.01).4. There was no correlation between age and the ability to respond to a saline load during the first month of life.5. Intrarenal blood flow distribution was measured by the radioactive microsphere technique. After saline infusion in the puppy there was an increase in outer cortical blood flow but inner cortical blood flow remained relatively constant. The result was a decrease in the ratio of inner to outer cortical blood flow (IC/OC ratio). In contrast the IC/OC ratio tended to increase in the adult dog after saline expansion.6. There was no correlation between the magnitude of change of sodium excretion and the change of intrarenal blood flow distribution in the puppy.7. These results confirm that the natriuretic response of the new-born dog kidney is less efficient than that of the adult dog. This is due primarily to the failure of the puppy kidney to decrease fractional sodium reabsorption. Although the new-born dog alters intrarenal blood flow distribution in response to saline loading this alteration does not appear to play a significant role in sodium excretion.