Evidence for central reorganization of ventilatory chemoreflex pathways in the cat during regeneration of visceral afferents in the carotid sinus nerve

There are two sets of peripheral arterial chemoreceptors in the cat, the carotid bodies innervated by the carotid sinus nerve and the aortic bodies with afferents in the aortic depressor nerves. Reflex stimulation of ventilation in response to hypoxia is abolished acutely after interrupting the sensory pathway from the carotid body chemoreceptors in the cat even though the reflex pathway from the aortic body chemoreceptors is intact. However, in chronically maintained preparations, there is a restoration of the hypoxic response which is mediated by the aortic chemoreflex pathway. It was proposed that restoration was due to a ‘central reorganization’ of chemoreflex pathways which followed interruption of the sensory pathway from the carotid bodies and that the reorganization enhanced the efficacy of the aortic ventilation chemoreflex. This proposal was tested in the present experiments by measuring reflex ventilatory and cardiovascular responses to electrical stimulation of the sensory nerves containing aortic and carotid chemoreceptor afferents following bilateral interruption of carotid sinus nerves and carotid body resection. Responses measured acutely (1–6 h) after interruption were compared with those measured 60–80 and 110–140 days later. At 60–80 days, a chemoreflex response (increase in tidal volume of ventilation) to stimulation of the interrupted carotid sinus sensory pathway was markedly attenuated while the response to stimulation of the uninterrupted pathway in aortic depressor nerves was enhanced. At 110–140 days, the tidal volume response to carotid sinus nerve stimulation was greatly enhanced while the aortic depressor nerve response declined from the elevated level. There were significant but less pronounced changes in the response of other ventilatory and cardiovascular variables to aortic depressor nerve and carotid sinus nerve stimulation.The results support the idea that there is a ‘central reorganization’ of chemoreflex pathways which is reflected functionally by changes in the efficacy of reflexes evoked from aortic depressor nerve and carotid sinus nerve. The changes are analagous to those occurring in somatic reflexes during regeneration of sensory nerves. It is suggested that the changes in efficacy of carotid sinus nerve reflexes are due to a degenerative loss of synapses of the central projections of interrupted carotid sinus nerve sensory axons (degenerative atrophy) and subsequent regenerative like changes (regenerative proliferation) in the central projections. The changes in the efficacy of aortic depressor nerve reflexes may be attributed to formation of new synapses by converging central projections of this uninterrupted pathway (reactive synaptogenesis) and subsequent regression of the newly formed synapses.     

The effect of pentobarbital anaesthesia upon the extracellular fluid volume in the dog,studied by continuous infusion and single injection methods

The effect of pentobarbital anaesthesia on the volume and ionic composition of the extracellular space was studied in adult male mongrel dogs with permanent catheters in aorta and pulmonary artery. The extracellular fluid volume (Q ^ec ) was determined with: a) methods based on equilibration of the indicator throughoutQ ^ec by continuous infusion; b) methods based on the assumption that after a single injection of indicator the plasma indicator concentration equals extracellular indicator concentration as long as the log plasma indicator concentration-time curve is linear; c) a single injection method based on a closed flow system model with a single inflow and a single outflow orifice. The measurements were made before and 30 and 90 min after induction of anaesthesia. Thirty minutes after induction of anaesthesiaQ ^ec as determined with the method sub a, had decreased by about 10% and remained so during the following 60 min. The values ofQ ^ec as calculated by the method sub c fairly agreed withQ ^ec as determined with the method sub a and also showed a decrease ofQ ^ec during pentobarbital anaesthesia. The procedures sub b overestimatedQ ^ec and yielded a seemingly higherQ ^ec during anaesthesia, because the boundary conditions for these procedures do not apply. The haemoglobin concentration decreased by about 10% and the lactate concentration by about 50%. The phosphate concentration increased by about 25% while the other electrolyte concentrations (Na⁺, K⁺, Mg²⁺, Ca²⁺, Cl^–, HCO ₃ ^– ) did not change. A respiratory acidosis developed during the first 30 min and almost disappeared in the following 60 min. Possible explanations for the pentobarbital-induced concentration ofQ ^ec are discussed.     

Responsiveness of the ANP providing system to volume load in conscious dogs

We examined in detail changes in arterial plasma ANP concentration in response to volume load in conscious dogs. In a 5-min volume load experiment, 18 ml/kg of isosmotic and isooncotic 3% Dextran 40 in saline was infused over a period of 5 min. Mean left atrial pressure (MLAP) increased transiently by 7.6±0.9 mm Hg. Plasma ANP level (P-ANP) did not significantly increase. Assayed P-ANP levels were corrected for hemodilution. Corrected P-ANP (C-ANP) significantly increased from 206±17 to 348±34 pg/ml. However, the level of C-ANP did not reach a steady state. No significant linear correlation was found between increases in MLAP and normalized C-ANP. In a 45-min volume load experiment, the elevated level of MLAP caused by the 5-min volume load was maintained for 40 min by supplemental infusion. C-ANP significantly increased from 196±18 pg/ml to 435±73 ng/ml. The level of C-ANP reached a steady state. A close linear correlation was observed between increases in MLAP and normalized C-ANP. However, the peak time of C-ANP lagged 10 min behind MLAP. These results indicate that it takes 10 min for P-ANP to reach a steady state in fully responding to a volume load, and that the long-term volume load is a prerequisite to the response of the ANP providing system.     

High-intensity intermittent running training improves pulmonary function and alters exercise breathing pattern in children

We investigated the effects of short duration running training on resting and exercise lung function in healthy prepubescent children. One trained group (TrG) (n = 9; three girls and six boys; age = 9.7 ± 0.9 year) participated in 8 weeks of high-intensity intermittent running training and was compared to a control group (ContG) (n = 9; four girls and five boys; age = 10.3 ± 0.7 year). Before and after the 8-week period, the children performed pulmonary function tests and an incremental exercise test on a cycle ergometer. After the 8-week period, no change was found in pulmonary function in ContG. Conversely, an increase in forced vital capacity (FVC) (+7 ± 4% ; P = 0.026), forced expiratory volume in one second (+11 ± 6% ; P = 0.025), peak expiratory flows (+17 ± 4% ; P = 0.005), maximal expiratory flows at 50% (+16 ± 10% ; P = 0.019) and 75% (+15 ± 8% ; P = 0.006) of FVC were reported in TrG. At peak exercise, TrG displayed higher values of peak oxygen consumption (+15 ± 4% ; P<0.001), minute ventilation (+16 ± 5% ; P = 0.033) and tidal volume (+15 ± 5% ; P = 0.019) after training. At sub-maximal exercise, ventilatory response to exercise was lower (P = 0.017) in TrG after training, associated with reduced end-tidal partial oxygen pressure (P<0.05) and higher end-tidal partial carbon dioxide pressure (P = 0.026). Lower deadspace volume relative to tidal volume was found at each stage of exercise in TrG after training (P<0.05). Eight weeks of high-intensity intermittent running training enhanced resting pulmonary function and led to deeper exercise ventilation reflecting a better effectiveness in prepubescent children.     

The cellular structure and lipid/protein composition of adipose tissue surrounding chronically stimulated lymph nodes in rats

To test the hypothesis that chronic immune stimulation of a peripheral lymph node induces the formation of additional mature adipocytes in adjacent adipose tissue, one popliteal lymph node of large male rats was stimulated by local injection of 10 microg or 20 microg lipopolysaccharide three times a week for 6 weeks. Adipocyte volumes in sites defined by their anatomical relations to the stimulated and homologous unstimulated popliteal lymph nodes were measured, plus adipocyte complement of the popliteal depot, and the lipid and protein content of adipocytes and adipose stroma. The higher dose of lipopolysaccharide doubled the mass of the locally stimulated lymph node and the surrounding adipose tissue enlarged by the appearance of additional mature adipocytes. Similar but smaller changes were observed in the popliteal adipose depot of the unstimulated leg and in a nodeless depot. The lipid content of the adipocytes decreased and that of the stroma increased dose-dependently in all samples measured but the changes were consistently greater in the depot surrounding the stimulated lymph node. The protein content of both adipocytes and stroma increased in samples surrounding the stimulated node. We conclude that chronic immune stimulation of lymphoid tissues induces the formation of more adipocytes in the adjacent adipose tissue. These findings suggest a mechanism for the selective hypertrophy of lymphoid-containing adipose depots in the HIV-associated adipose redistribution syndrome.     

Hyperglycemic and Hyperosmolar Responses to Graded Hemorrhage

Changes of the arterial plasma osmolality and of the glucose concentration were followed during a 30 min period of graded hemorrhagic hypotension (80, 50, and 30 mmHg) in the cat. Bleeding evoked a significant plasma hyperosmolality at all three hypotension levels and the responses were quantitatively related to the degree of hypotension. An approximate steady state increase in the arterial plasma osmolality was reached about 20 min after the start of the bleeding and it then averaged 8, 20, and 25 mOsm/kg H₂O at 80, 50, and 30 mmHg, respectively. Bleeding also evoked an increase in the plasma glucose concentration, which almost entirely accounted for the observed hyperosmolality, especially at 80 and 50 mmHg. In late stages of hypotension at 30 mmHg, elevated plasma lactate and potassium concentrations contributed to the overall hyperosmolality. — Previous hemorrhagic hypotension experiments at 50 mmHg (Järhult 1975 b) have shown that hyperosmolality serves as an important regulator of the plasma and extracellular fluid volumes during bleeding. The present results indicate that such an osmolar compensatory mechanism is operating over wide ranges of hemorrhagic hypotension.     

Development and loss of toluene diisocyanate reactivity: immunologic,pharmacologic, and provocative challenge studies

Toluene diisocyanate (TDI) sensitivity accompanied by nonspecific bronchial hyperresponsiveness occurs in approximately 5% of occupationally exposed workers. We report the case of a 32-yr-old worker followed longitudinally after removal from isocyanate exposure. TDI reactivity was lost 11 mo after removal from exposure and nonspecific bronchial hyperresponsiveness resolved after 17 mo. Bronchial reactivity to radishes (Raphanus sativus), which developed concurrently with TDI reactivity, was lost 2 yr later. Immunopharmacologic results show that the worker's initial decreased ability of lymphocytes to produce cyclic AMP returned to near normal after 2 yr. IgE antibodies to a human serum albumin tolyl monoisocyanate conjugate were still present at this time.     

Extracellular ionic and volume changes: The role in glia—Neuron interaction

Activity-related changes in extracellular K⁺ concentration ([K⁺]_e), pH (pH_e) and extracellular volume were studied by means ofion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3–14 days of age (P3–P14). Concomitantly with the ionic changes, the extracellular space (ECS) volume fraction (α), ECS tortuosity (λ) and non-specific uptake (k′), three parameters affecting the diffusion of substances in nervous tissue, were studied in the rat spinal cord gray matter. In adult rats, repetitive electrical nerve stimulation (10–100 Hz) elicited increases in [K⁺]_e of about 2.0–3.5 mm, followed by a post-stimulation K⁺-undershoot and triphasic alkaline-acid-alkaline changes in pH_e with a dominating acid shift. The ECS volume in the adult rat occupies about 20% of the tissue, α = 0.20 ± 0.003, λ = 1.62 ± 0.02 and k′ = 4.6 ± 0.4 × 10⁻³s⁻¹ (n = 39). In contrast, in pups at P3–P6, the [K⁺]_e increased by as much as 6.5 mm at a stimulation frequency of 10 Hz, i.e. K⁺ ceiling level was elevated, and there was a dominating alkaline shift. An increase in [K⁺]_e as large as 1.3–2.5 mm accompanied by an alkaline shift was evoked by a single electrical stimulus. The K⁺ ceiling level and alkaline shifts decreased with age, while an acid shift, which was preceded by a small initial alkaline shift, appeared in the second postnatal week. In pups at P1–P2, the spinal cord was X-irradiated to block gliogenesis. The typical decrease in [K⁺]_e ceiling level and the development of the acid shift in pH_e at P10–P14 were blocked by X-irradiation. Concomitantly, continuous development of glial fibrillary acidic protein positive reaction was disrupted and densely stained astrocytes in gray matter at P10–P14 revealed astrogliosis.The alkaline, but not the acid, shift was blocked by Mg²⁺ and picrotoxin (10⁻⁶m). Acetazolamide enhanced the alkaline but blocked the acid shift. Furthermore, the acid shift was blocked, and the alkaline shift enhanced, by Ba²⁺, amiloride and SITS. Application of glutamate or gamma-aminobutyric acid evoked an alkaline shift in the pH_e baseline at P3–P14 as well as after X-irradiation. The results suggest that the activity-related acid shifts in pH_e are related to membrane transport processes in mature glia, while the alkaline shifts have a postsynaptic origin and are due to activation of ligand-gated ion channels.At P4–P6, the ECS volume was almost double that in adult rats, α = 0.37 ± 0.01 (n = 17), the ECS tortuosity was significantly higher, λ = 1.78 ± 0.02, while the non-specific uptake was not significantly different, k′ = 3.61 ± 0.56 × 10⁻³ s⁻¹. The α gradually decreased to about 24% at P12. In adult rats, electrical or adequate stimulation evoked a shrinkage of the extracellular space by 20–50%, while no significant changes in ECS volume were found in P3–P6. We conclude that the [K⁺]_e ceiling level, character of the pH_e transients, the size of the ECS volume and the activity-related ECS shrinkage are closely related to gliogenesis.