Biochemical, biomechanical, and physical changes in the skin in an experimental animal model of therapeutic tissue expansion.

Biochemical, biomechanical, and physical changes occurring in the skin during tissue expansion have been studied using an animal model in which a Silastic expander was inserted into the peritoneal cavity. Forty-eight Sprague-Dawley rats were divided into four groups to be studied at 4, 8, 16 and 32 days after expansion. In the experimental animals (6 per group) the expander was inflated by a single injection of 120 ml of saline. Sixteen hours prior to sacrifice each animal received a single injection of tritiated proline. Sixteen days after expansion both the specific activity and the total content of hydroxyproline in the skin were significantly elevated in experimental animals. Intrinsic skin tension increased dramatically at the time of inflation but fell almost to control values at the end of 32 days. Skin thickness, initially decreased, returned to normal by the end of the experiment. There were no significant differences in breaking strengths between skin from experimental and control animals. Skin surface area, initially increased by stretching at the time of inflation, increased further between Days 0 and 8, possibly as a result of stress relaxation combined with enhanced remodelling of connective tissue macromolecules, and again from Days 24 to 32. We conclude that, during tissue expansion, there is a net accumulation of collagen in the skin and that this allows the local cellular environment to return to normal with respect to pressure and/or tension.

Intracellular electrical activity in circular muscle of canine colon.

In vivo and extracellular in vitro studies of colon muscle have led to a great deal of disagreement on the characteristics of slow wave activity. As intracellular recordings of electrical activity in single cells give clear records which are easier to analyse, we used this method to study the slow wave activity of the circular muscle of three different parts of the canine colon. Mucosa was removed from segments of proximal, mid and distal canine colon and specimens from each segment were mounted in an organ bath perfused with oxygenated Krebs' solution. Membrane potential, amplitude and frequency of slow waves were measured using intracellular electrodes. Slow wave activity was present at a single, continuous frequency of 4-6 cpm in the circular muscle at all the sites studied in canine colon. There was no significant frequency gradient along the colon: the membrane potential and amplitude of slow waves did not differ significantly in the three parts of the colon.

Sleep of shiftworkers within the arctic circle.

The sleep of shiftworkers in the Arctic has been investigated using electroencephalography. The subjects were studied four times a year over a 2-year period. There was a trend toward less restful sleep during the autumn and winter months, but otherwise sleep at various times of the day was similar to that of individuals elsewhere. This would suggest that sleep disturbance in polar shiftworkers can be managed in a similar way to that of shiftworkers in temperate regions.

Origin of slow waves in the canine colon.

The objectives of this work were to determine the origin of slow wave activity in the canine colon, to examine the slow wave characteristics in the circular and longitudinal muscle layers, and to examine the roles played by each of these layers in the generation of this activity. Extracellular electrical activity was recorded in vitro from strips of intact muscle wall and from isolated circular and longitudinal muscle using either multiple electrodes applied to one side of the specimen or two electrodes applied simultaneously to opposite sides of the tissue. Intracellular electrical activity was also studied in intact muscle, in isolated circular muscle, and in isolated longitudinal muscle. Slow waves were recorded extracellularly from circular and longitudinal muscle when the two layers formed the intact muscle wall; they were also recorded from isolated circular muscle, but not from isolated longitudinal muscle. Removal of the submucosa from the circular muscle surface abolished slow waves recorded from both isolated circular muscle and the intact specimen. Exposure of the mucosal surface of isolated circular muscle to a hypertonic solution of KCl abolished slow waves, while exposure of the serosal surface to the same concentrations had no effect. Slow waves are not generated in longitudinal muscle. Slow waves in circular muscle are dependent on the integrity of the junction between the submucosa and the innermost circular layer.

In vitro electrical activity in human colon.

Extracellular electrical activity was measured in vitro in 28 specimens of human colon taken at the time of operation. The mucosa was removed, and the muscle strips were mounted in an organ bath irrigated with oxygenated Krebs. Records were made from 3-7 silver/silver chloride electrodes placed directly on the circular muscle, for periods of 15-30 min. Data were stored on magnetic tape, digitized, analyzed by the fast Fourier transform method and plotted in three-dimensional form (signal power vs. frequency vs. time). Some plots showed a single frequency peak in the range 2-9 cpm, which was present throughout the study. However, multiple peaks were frequently seen and were of two types: (a) peaks of two or three closely related frequencies in the 2-9 cpm range, which divided and fused during the recording time. The power of the fused peak was greater than that of the components. And (b) peaks at frequencies which were integer multiples of the fundamental frequency; we interpret these to be the second and third harmonics of the fundamental frequency. When the fundamental frequency peak developed into several components, similar components also appeared at their individual harmonic frequencies, i.e., the second harmonic components were separated by twice the interval between the fundamental components. We conclude that only one fundamental frequency of electrical activity exists in any one site in human colon. Multiple frequencies are due either to the simultaneous recording from two or more poorly coupled electrical oscillators or to harmonics of the fundamental frequency.

Effects of histamine and antihistamines on the kinetics of carbon dioxide in the rat.

We have investigated the effects of chlorpheniramine (an H1 histamine inhibitor) and metiamide (an H2 inhibitor) on response to 14C pulse-labeling of carbon dioxide in the rat in the presence and absence of histamine. Neither chlorpheniramine nor metiamide alone had any effect upon the gastric venous/arterial ratio (VG/A) or the peripheral venous/arterial ratio (Vp/A). As in the case with no drug present, Vp/A rose with time following pulse-labeling to a value of 1.15-1.20. The presence of a preexisting steady-state infusion of histamine caused no changes in the ratios in the presence or absence of the inhibitors. The inhibitors did completely abolish the oscillations of both VG/A and Vp/A caused by initiation of histamine infusion coincident with the pulse-labeling. The results suggest that the histamine effects are largely mediated through H1 receptors.

Carbon dioxide balance in rat stomach and peripheral tissue: effects of histamine.

Total carbon dioxide content of arterial, gastric venous, and peripheral venous blood of the rat has been measured by a gas extraction-gas solid chromatographic technique. In control animals total contents were 24 to 29 mmol/l and the venous/arterial ratio 1.148 +/- 0.020 (xav +/- SEM). Net change of carbon dioxide content (delta CO2) was 1.17 +/- 0.56 and 1.11 +/- 0.45 mmol/l in gastric and peripheral circulations and these were not significantly different from each other or zero. Infusion of histamine at 10 mg/kg/h led to oscillations in delta CO2 with peaks as high as 4.7 mmol/l and a period of 20 min. Similar oscillations occurred in the venous/arterial ratio with values up to 1.35. The results confirm previous reports of oscillations of carbon dioxide venous/arterial ratios induced by histamine as revealed by pulse radiolabeling experiments. The positive, if oscillatory, carbon dioxide balance in the presence of histamine supports the concept of sequestration of carbon dioxide in tissue with subsequent release on histamine stimulation.

Effect of histamine upon the dynamics of carbon dioxide.

The dynamics of carbon dioxide in both gastric and peripheral circulation of rat were studied using H14CO3--. In the absence of histamine infusion the peripheral venous/arterial ratio Vp,/A rose from less than 1.0 to almost 1.2 while the gastric ratio VG/A fell from initial values of about 2.4 to 1.2. Steady histamine infusion speeded approach of both ratios to 1.2. During transient conditions after beginning or end of histamine infusion both ratios were initially depressed to values near zero. The ratios then both rose, showing damped oscillations with a twenty-minute period. The data show a marked effect of histamine on both peripheral and gastric CO2 dynamics, even though in the resting state the two circulations have very different dynamics.

Comparative temperature dependence of (Na+ + K+)-ATPase.

The temperature dependence of (Na+ + K+)-ATPase was measured, utilizing preparations of enzyme from heat and kidney of rats, hamsters, guinea pigs, ground squirrels, turtles, chickens, and ducks. The two hibernating species, hamsters and ground squirrels, were studied awake at normothermia and hibernating at 4 degrees C. The results for every species except the turtles showed the same temperature dependence established for (Na++K+)-ATPase from rabbit kidney with a quasi-linear dependence above 15 degrees C and little or no activity below 15 degrees C. Turtle enzymes showed a broad activity versus temperature curve with a fall-off at high and low temperatures. The data in all cases, including the turtle data, may be fitted by a previously described thermodynamic kinetic model. Further, the model will fith the turnover or decrease in enzyme activity at higher temperatures observed in a number of cases. These results do not support the widely imputed ion pumping role for (Na++K+)-ATPase.