Cardiac output changes during hyperbaric hyperoxia.

OBJECTIVES: Increased ambient pressure and oxygen partial pressure (pO2) influence cardiovascular regulation during diving and caisson work. We measured the cardiac output (Q) in subjects who practiced moderate work at a usual diving depth of 30 m. METHODS: In 23 healthy male Navy divers who performed steady state bicycle exercises (100 W workload) in a hyperbaric chamber Q was measured by a CO2-rebreathing technique at normal pressure (100 kPa) and at raised ambient pressure (400 kPa), in a random order. During the rebreathing maneuver the subjects were exposed to pO2 values which theoretically may have reached a maximum value of 87 kPa (normobaric) and 388 kPa (hyperbaric). During the experiments the ambient temperature ranged between 22 and 25 degrees C. RESULTS: There was a significant decrease of the directly measured Q, heart rate (HR) and the calculated stroke volume at depth when compared with normoxic and normobaric exercise. The decrease of Q amounted to 64% of the normobaric value (8.9 l min-1 versus 13.9 l min-1). The mean HR decreased from 104.7 min-1 (100 kPa) to 94.0 min-1 (400 kPa). The calculated mean stroke volume decreased from 133 ml (100 kPa) to 96 ml (400 kPa). CONCLUSIONS: During hyperoxic hyperbaria the peripheral vascular tonus increases due to the consecutively increased arterial oxygen content. The cardiac output may correlate to the peripheral vasoconstriction and is therefore indirectly influenced by elevation of inspiratory pO2 i.e. during the rebreathing maneuver.

Respiratory effects of a single dive to 50 meters in sport divers with asymptomatic respiratory atopy.

Increasing popularity of sports diving makes it likely that subjects with allergic respiratory diseases will be involved in diving with self contained underwater breathing apparatus (scuba). The present study evaluated the effects of a single scuba-dive on pulmonary function in subjects with respiratory atopy. Specific airways conductance (sGaw), residual volume (RV), forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), mid expiratory flow at 50% of FVC (MEF50), and transfer factor for carbon monoxide (TLCO) were measured in 9 sport divers with a history of hay fever and 9 matched healthy sport divers (control) before, 3 hours and 24 hours after a wet hyperbaric chamber dive to a depth of 50 m. Airway hyperresponsiveness (AHR) was assessed by methacholine challenge 4 weeks after the dive. Atopic subjects and controls did not differ with respect to anthropometric data, diving experience, and predive lung function. A 3% reduction in FVC was found 24h after the dive (p < 0.05) in both groups, whereas sGaw decreased by 15% 24 h after the dive (p < 0.05) in the subjects with respiratory atopy only. Postdive changes in RV, FEV1, MEF50, and TLCO did not reach level of statistical significance. AHR was obtained in 8/9 subjects with respiratory atopy. We conclude that subjects with atopic sensitization and asymptomatic AHR may be more susceptible to effects of diving on pulmonary function.

Respiratory pattern after wet and dry chamber dives to 0.6 MPa ambient pressure in healthy males.

The purpose of this study was to evaluate respiratory effects of wet and dry hyperbaric chamber dives to 0.6 MPa ambient pressure in healthy males. There were 19 and 22 subjects who participated in two series of dives with a bottom time of 15 min and decompression times of 28 and 17 min, respectively. Airways conductance, residual volume, forced vital capacity, forced expiratory volume in 1 sec, mid expiratory flow at 25, 50 and 75% of FVC, and diffusion capacity for CO were measured before the dives, after 3 h, and after 24 h. Multivariate analysis of covariance revealed no statistically significant effects of time or the interaction between time and dry or wet environment on the measured lung function parameters. These findings suggest first that even deep air dives may not necessarily affect pulmonary function, and second, that factors related to the particular wet environment do not seem to contribute to lung function changes after dives.

Cold stress, reverse T3 and lymphocyte function.

Following a recently reported rise in serum reverse triiodothyronine levels in response to cold exposure, an initial in vitro study has been carried out on human lymphocyte function. The first part of the study demonstrated that the uptake of rT3 on lymphocyte nuclear receptors increased as the rT3 concentration was raised above the normal serum level. The binding is competitive with triiodothyronine. The lymphocytes were harvested from venous blood donated by young male U.S. naval personnel. The second part of the study involved lymphocyte proliferation assays carried out with the addition of increasing amounts of rT3. Both non-specific (three different mitogens) and specific (recall antigen) stimuli were used. There was an indication that lymphocyte function is depressed by increasing serum concentration of rT3. However, with a small number of test subjects and a resulting low statistical power, it was not possible to establish a statistically significant association. Lymphocytes from umbilical cord blood, which has a very high level of rT3 compared to that in normal adult sera, were also found to have a much reduced lymphocyte stimulation index. The requirements for a more definitive investigation are outlined.

Experimental design and estimation of parameters in complex radioligand binding systems.

A computer was used to simulate data from typical radioligand binding experiments with a 2-site competitive-allosteric model of a receptor. The 4 equilibrium parameters of this model cannot be estimated by fitting the model to equilibrium data. Data from simulations of association experiments give satisfactory estimates of the 9 competitive-allosteric model parameters. From the kinetic parameters, equilibrium constants may be calculated. Combining data from equilibrium simulations with data from association simulations provided estimates of the model parameters with smaller standard deviations. A further improvement in design was shown possible by including simulated experiments in which receptor was preincubated with inhibitor before adding ligand. This improvement was documented using Monte Carlo replications of parameter estimates using competing experimental designs. Replications also revealed certain biases in the parameter estimates and could provide a means of estimating those biases when parameter estimates are made using experimental rather than simulated data. Simulations offer a powerful tool in planning experiments designed to estimate kinetic parameters of a receptor system. This is especially true with complex systems that may require pooling data from different kinds of experiments in order to estimate the kinetic parameters.

Exercise effects on central venous nitrogen tensions after simulated non-decompression dives.

In five subjects we examined the effect of exercise on the pattern of central venous (right atrial) N2 tensions (PVN2) after ascent from simulated non-decompression dives. The dives consisted of exposure to air at 3 bar for 20 min with 10 min of exercise (workload 75 W) at depth to achieve near-complete N2 saturation of the muscles. After the dive the subjects rested or, on another day, exercised for 30 min (workload 100 W) starting 10 min after completing the ascent. Blood samples taken every 10 min until the 60th min and 90 min after the dive were analyzed for PVN2 using a manometric Van Slyke apparatus. The amount of N2 eliminated was estimated from the PVN2 by adapting the Fick principle. Immediately after the ascent, PVN2 were 950 +/- 39 and 942 +/- 27 mmHg, respectively, in the rest and experiment series. In the rest experiments PVN2 continuously decreased to 606 +/- 8 mmHg 90 min after the dive, remaining significantly higher (P < 0.05) than before the dive. Exercise caused the PVN2 to increase beyond the corresponding levels of the rest experiments (P < 0.05 at 20 and 30 min exercise). After the exercise PVN2 rapidly declined, reaching predive levels 60 min after the ascent. Exercise increased N2 elimination to 970 +/- 143 ml, whereas it had been 311 +/- 61 ml (P < 0.05) in the corresponding phase of the rest experiments. We conclude that if extensive supersaturation and bubble formation can be avoided, such as probably was the case in our shallow non-decompression dives, exercise after the ascent accelerates N2 elimination.

Mechanisms of beta-adrenergic stimulation of cardiac Ca2+ channels revealed by discrete-time Markov analysis of slow gating.

Individual cardiac Ca2+ channels cycle slowly between a mode of gating in which the channel is available to open, and one in which the channel remains silent. The regulation of this multisecond cycling process by isoproterenol was investigated by single-channel recording and the development of a discrete-time Markov model that describes the slow switching among modes in terms of (de) phosphorylation reactions. The results provide evidence that isoproterenol increases Ca2+ channel activity by a reciprocal regulatory mechanism: not only is the phosphorylation rate of the channel increased, but also the dephosphorylation rate decreased. The discrete-time Markov formalism should prove useful as a general tool for understanding the mode switching demonstrated by a number of ionic channels.

Equipotent allosteric effect of W84 on [3H]NMS-binding to cardiac muscarinic receptors from guinea-pig, rat, and pig.

W84 (hexamethylene-bis-[dimethyl-(phthalimidopropyl)-ammonium bromide]) is an experimental antidote against organophosphorus poisoning and has been found to affect muscarinic cholinoceptors allosterically. The attempt was made to test whether the W84-action on muscarinic cholinoceptors depends on the species. For this purpose, the effect of W84 on the binding of [3H]N-methylscopolamine ([3H]NMS) was investigated in membrane-suspensions from the hearts of guinea pigs, rats, and pigs in 3 mM MgHPO4, 50 mM Tris, pH 7.3, at 23 degrees. W84 inhibited [3H]NMS-binding in the three membrane suspensions with similar potency (half-inhibitory concentration IC50: 2-5 microM). To evaluate the allosteric activity of W84, its effect on the dissociation of [3H]NMS was determined. At 3 microM, W84 diminished the rate of [3H]NMS-dissociation to about 20% of the control in three suspensions. At 100 microM of W84, [3H]NMS-dissociation was almost prevented. In conclusion, W84 acted equally on the cardiac cholinoceptors of guinea pigs, rats, and pigs, respectively. It can be anticipated that M2-cholinoceptors of other species would likewise be affected by W84.

Interaction of the hexamethonium derivative W84, an allosteric effector at muscarinic cholinoreceptors, with rat brain nicotinic binding sites.

The hexamethonium derivative W84 (hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)-ammonium bromide]) combined with atropine has an overadditive protective action against organophosphorus intoxications. It affects allosterically the binding of (-) [3H]N-methylscopolamine [(3H]NMS) to muscarinic cholinoceptors. Because nicotinic receptors are involved in organophosphorus intoxications, the interaction of W84 with nicotinic cholinoceptors was investigated. (-) [3H]nicotine (2.5 nM) was used to label nicotinic binding sites in rat brain membranes in 50 nM Tris, pH 7.3 at 23 degrees. Under control conditions, (-) [3H]nicotine-binding revealed a KD of 4 X 10(-9) M and a Bmax of 53 fmol/mg membrane protein. W84 inhibited (- ) [3H]nicotine-binding with an IC50 of 3 X 10(-5) M by reducing the binding affinity. The IC50 of hexamethonium was 20 X 10(-5) M. At 10(-4) M, W84 did not affect the dissociation rate of (-)[3H]nicotine, suggesting a lack of allosteric activity. For sake of comparison, the action of W84 was checked on [3H]NMS-binding (control: KD approximately 1 X 10(-9) M, Bmax approximately 500 fmol/mg prot). W84 inhibited the binding of [3H]NMS (0.5 nM) with an IC50 of 1.5 X 10(-9) M. At 10(-4) M, W84 prevented [3H]NMS-dissociation almost completely, thus displaying the allosteric action at muscarinic cholinoceptors. In conclusion, the results of the (-)[3H]nicotine-binding experiments point to a pure competitive action of W84 at nicotine cholinoceptors, lacking any allosteric effect. This competitive action may contribute to the protective effect of W84 in organophosphorus poisoning.

[Computer-assisted assessment of the 24-hour blood pressure profile in essential and secondary hypertensive patients]. / Computergestützte Auswertung von 24-Stunden-Blutdruckprofilen bei essentiellen und sekundären Hypertonikern.

In 17 essential hypertensives, 13 secondary hypertensives and 9 normotensives, noninvasive 24 h blood pressure monitoring was performed. By a computer-aided evaluation according to the Cosinor method, circadian periodicity was quantified and expressed as a coefficient of periodicity in %. This coefficient for systolic pressure was higher in essential hypertensives and normotensives than in secondary hypertensives (42.9 +/- 18.0 et 43.0 +/- 16.7 versus 28.2 +/- 17.7; p less than 0.05). The circadian periodicity of diastolic pressure showed no significant differences. Despite the large overlap, coefficients of periodicity below 20% for systolic pressure may suggest secondary hypertension.

[Relations between the cortical DC potentials and the K+ concentration of the blood and cerebral cortex extracellular space in reversible asphyxia]. / Beziehungen zwischen kortikalen DC Potentialen und der K+-Konzentration im Blut und Extrazellulärraum der Hirnrinde bei reversibler Asphyxie.

The relationship between changes of the cortical DC potential and the K+ concentration gradient across the blood-brain barrier (BBB) was studied in the rat brain during short ventilatory arrest. For this purpose K+ concentrations were measured simultaneously in the extracellular space of the cerebral cortex and in the streaming blood of the carotid artery and the superior sagittal sinus. For measurements ion-selective micro- and macro-electrodes based on the K+ ionophore valinomycin were used. During reversible asphyxia free K+ concentrations in the circulating blood and in the extracellular fluid of the brain tissue increased and re-decreased with different time courses. The resulting difference between the electromotive forces of the ion-selective signals resembled the course of the cortical DC potential during the initial phase of the ventilatory arrest during the post-asphyxiation period. The results suggest that during these events the cortical tissue including the BBB behaves like a K+-selective membrane which is probably located at the blood-brain interface. It is concluded that the capillary-glial complex may principally contribute to the generation of DC shifts associated with the asphyxiation process.