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A voltage clamp circuit is described which permits the measurements of current transients in membranes with time constants of the order of microseconds. The resistance R_s in series with the membrane is compensated for by a current feedback circuit which produces a rapid charging of the membrane capacitance C. It is possible by this arrangement to reduce the charging period to a value considerably shorter than the time constant R_sC.

The hydraulic conductivity of the rat proximal tubular wall was determined using colloidal solutions perfused in short (50--200 mum) (SMP) or long (90--200 mum) (LMP) proximal tubular segments. In SMP human serum albumin (HSA) or polyvinylpyrrolidone (PVP) was added to raffinose solutions. A Lp of 0.019 nl-min-1-mm-1-mm Hg-1 was found when high colloid concentrations were used while values of 0.055--0.092 were found when low colloid concentrations were used. In other experiments, the Lp was determined by perfusing short tubular segments with pure raffinose solutions. A value of 0.015 nl-min-1-mm-1-mm Hg-1 was found. This is twice the value found when raffinose solutions were perfused through long tubular segments and it is concluded that the short microperfusion technique overestimates Lp with a factor of two. When microperfusions of long tubular segments were conducted, PVP was added to an equilibrium solution consisting of NaCl (110 mM) and raffinose (80 mM). Lp was found to be 0.018--0.021 when high colloid concentrations were used, while a value of 0.029 was found when a low colloid concentration was used. As found in both SMP and LMP a decrease in Lp's with increasing colloid concentrations indicates that a significant influence of radial concentration differences is highly probable. It is therefore suggested that the highest Lp derived when using the lowest colloid concentrations represents the best estimate. With this Lp value (0.03--0.05 nl-min-1-mm-1-mm Hg-1) and the existing transtubular hydrostatic and oncotic pressure difference it can be calculated that these passive forces might constitute the driving force for 1/3 of the fluid reabsorbed in the proximal tubule.

The time course of relaxation of the electric current following steps in the applied potential across lipid bilayer membranes has been measured. The membranes were made cation-selective by the addition of nonactin. To permit the measurement of very short time constants a voltage clamp device was developed in order to reduce the charging period to less than 1 musec, regardless of the magnitude of the series resistances in the external solutions. It was possible by this method to establish the presence of two electric processes, which were found to behave differently with respect to temperature, applied potential and external solution conditions. The rapid process (tau approximately 10 musec) was interpreted in terms of the electric parameters of the polar part of the membrane according to the theory developed by Hägglund and Sandblom (T.I.T.J. Life Sic. 2: 107, 1972). The second process (tau approximately 100 musec) showed a behavior consistent with the model of Stark, Ketterer, Benz and Läuger (Biophys. J. 11:981, 1971), which considers the different rate constants involved in the net transfer of carriermediated ion transport across bilayer membranes.

Objective:

To examine the effects of square wave, sinusoidal, and linear inspiratory pressure waveforms during pressure-controlled assist/control ventilation on the firing pattern of pulmonary stretch receptors and phrenic nerve activity.

Design:

Experimental, comparative study.

Setting:

Research laboratory at a university biomedical center.

Subjects:

Nine anesthetized, endotracheally intubated young cats (2.5–3.4 kg).

Intervention:

With interposed periods of continuous positive airway pressure (0.2 kPa), each cat was exposed to periods of assist/control ventilation with three different pressure waveforms, where the peak inspiratory pressure (0.74 ± 0.13 kPa), end-expiratory pressure (0.2 ± 0.02 kPa), and tidal volume (14.9 ± 5.22 mL/kg) were kept constant. Preset controlled ventilator rate was set below the rate of spontaneous breathing, and the mechanical inflation time equaled the inspiratory time during spontaneous breathing on continuous positive airway pressure.

Measurements and Main Results:

Respiratory rate and arterial blood gases did not change between the three pressure waveforms during assist/control ventilation. Peak pulmonary stretch receptor activity was lower and mean phrenic nerve activity higher during continuous positive airway pressure than during assist/control ventilation (p < .05). Peak inspiratory pulmonary stretch receptor activity was the same with all three pressure waveforms (82 ± 17 impulses·sec^-1) but occurred earlier with square wave than with sinusoidal or linear pressure waveforms (p < .05). The total number of impulses in the phrenic nerve activity burst was smaller with square wave than with the other two pressure waveforms (0.21 ± 0.17 vs. 0.33 ± 0.27 and 0.42 ± 0.30 arbitrary units;p < .05), and the phrenic nerve activity burst duration was shorter with square wave (1.10 ± 0.45 vs. 1.54 ± 0.36 and 1.64 ± 0.25 secs;p < .05).

Conclusion:

Square wave pressure waveform during pressure-controlled assist/control ventilation strongly inhibits spontaneous inspiratory activity in cats. One mechanism for this inhibition is earlier and sustained peak pulmonary stretch receptor activity during inspiration. These findings show that differences in inspiratory pressure waveforms influence the spontaneous breathing effort during assist/control ventilation in cats.

The driving force for creation of channels in gastric mucus, for acid and pepsin transport, ismost probably the hydrostatic pressure generated within the gastric gland lumen. The aim ofthis study was to investigate the origin and regulation of the glandular pressure. In addition,several parameters known to play an important role in mucosal protection were investigated inrelation to glandular pressure. The study was performed in vivo in exposed gastric mucosa ofInactin^@-anesthetized rats. Glandular pressure, epithelial cell surface pH and mucus gelthickness were measured with microelectrodes, mucosal blood flow by laser Dopplerflowmetry, and mucosal permeability by clearance of ⁵¹Cr-EDTA from blood to lumen.Specimens of mucosa were also investigated immunohistochemically.

Actin immunostaining revealed muscle strands arising from muscularis mucosa and branchingat the gastric pits. Vasoactive intestinal peptide (VIP)- containing nerve fibers were found inclose relation to these muscle strands. Administration of VIP decreased glandular pressure,probably by relaxing the muscle strands.

The glandular pressure decreased along with the reduction in acid/volume secretion whensecretagogue infusion was terminated or when acid secretion was blocked by ranitidine.Omeprazole administration, in contrast, sustained or increased the pressure despite totalinhibition of acid secretion, probably by increasing resistance to outflow of the glands,resulting in intraglandular volume accumulation and dilatation of the glands.

Prostaglandin E₂ greatly increased glandular pressure in low doses that did not affect bloodflow, acid secretion or mucus thickness, while indomethacin decreased the pressure.Aggressive factors (ethanol and HCl) applied topically increased the pressure, probably byreleasing prostaglandins, since indomethacin pretreatment inhibited this response.

Topical administration of acid (pH 1) increased permeability and blood flow in the nonacid-secreting mucosa and decreased epithelial cell surface pH. High endogenous acid secretion ori.v. infusion of bicarbonate protected the mucosa.

Conclusions: The histologically observed mucosal muscles provide a morphological basis forcreation of an intraglandular pressure. Despite total inhibition of acid secretion some glandularpressure always remains. Endogenous prostaglandins are probably important for maintenanceof a high glandular pressure. The acid-secreting mucosa has a better buffering capacity byvirtue of increased bicarbonate delivery from the parietal cells through the surface epithelium tothe mucus.