Effect of static load on matrix synthesis rates in the intervertebral disc measured in vitro by a new perfusion technique.

The effect of static loading on matrix synthesis was measured in intact bovine coccygeal discs. The discs were maintained at 37 degrees C in a humid atmosphere and were perfused across their upper and lower surfaces for as long as 8 hours with media containing radioisotopes (3H-proline and 35S-sulphate) via porous filter disks embedded in Perspex (Plexiglas) holders. Static loads were applied to the disc with use of weights. The activity of free, nonincorporated isotope in the centre of the disc was monitored continuously with a microdialysis probe. Incorporated tracer in different regions of the disc was determined at the end of each experiment from the activity of the nondialysable tracer. Free tracer activity rose steeply over the first 3-4 hours of perfusion, as tracer diffused into the disc, and reached a steady value after 5-6 hours, as expected from diffusion theory. The rate of tracer incorporation estimated from the integrated value of free tracer concentration was constant for as long as 8 hours. Incorporation rates varied across the disc: the highest rates were in the inner layer of the annulus fibrosus, and the lowest rates were in the outer layer of the annulus. The rates for both 35S-sulphate and 3H-proline varied with load. The rates were lowest in the nucleus pulposus and the inner layer of the annulus fibrosus with a 0.5 kg load, and they almost doubled as the load was increased to 5-10 kg. Heavier loads (15 kg) led to a decrease in incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of tolbutamide on cerebral blood flow during hypoxia and hypercapnia in the anaesthetized rat.

The increase in blood flow in the cerebral cortex of the anaesthetized rat during hypoxia and hypercapnia was investigated. Cerebral blood flow (CBF) was measured using the hydrogen clearance method with acutely implanted platinum electrodes. Hypoxia (PaO2 35.3 +/- 2.4 Torr) and hypercapnia (PaCO2 68.1 +/- 5.1 Torr) increased basal CBF from 76.3 +/- 9.0 ml/100g/min to 168.1 +/- 20.1 ml/100g/min and 162.4 +/- 31.9 ml/100g/min respectively. The sulphonylurea tolbutamide (1mM in 1%DMSO) had no significant effect on CBF in hyperoxia or in hypercapnia. However, it attenuated the increase of CBF during hypoxia by 66 +/- 11% (p < 0.01). This suggests that opening of tolbutamide-sensitive potassium channels may be involved in the process of hypoxic vasodilation in the rat cerebral cortex.

Effect of potassium on ventilation in the rhesus monkey.

Increasing the concentration of arterial plasma K+ to 6-8 mM increased ventilation in two sedated analgesic-treated rhesus monkeys who had their end-tidal CO2 held constant during euoxia (arterial oxygen pressure, Pa,O2, ca 100 Torr) and hypoxia (Pa,O2, ca 40 Torr). During euoxia and hypoxia, hyperkalaemia increased ventilation up to 40 and 250%, respectively. This effect was reduced in euoxia and virtually abolished in hypoxia following an abrupt switch to 100% oxygen. Thus the ventilatory response of this primate to hyperkalaemia is at least as sensitive as that of the cat and if hypoxia is added the two stimuli generate a powerful drive to breathing.

Distensibility of single capillaries and venules in the rat and frog mesentery.

The distensibility characteristics of single microvessels in the mesentery of frogs and rats has been determined by a new technique capable of resolving a change in radius of about 0.01 micron in vivo. Two water insoluble immiscible oils were micro-injected into occluded segments of the vessels. Since the volume of the oil remained constant, the position of the interface at different applied pressures could be used to determine changes in vessel diameter. The stress/strain relationship of capillaries and venules in the frog mesentery and venules in the rat mesentery were determined and found to be similar to each other. Vessel diameters increased by up to 15% over the whole pressure range used but in a markedly non-linear manner, stiffening at higher strains. It is suggested that the basement membrane has the appropriate properties to explain this behaviour.

The effect of phenylephrine upon arterial pressure, carotid sinus radius and baroreflex sensitivity in the conscious greyhound.

1. A method for recording carotid sinus diameter in conscious dogs has been developed, using an ultrasound transit time technique. We have used this method to measure the distensibility of the carotid sinus in resting animals, and we have investigated the effect of injecting the vasoactive drug phenylephrine on the mechanical behaviour of the sinus wall. 2. Baroreflex sensitivity was measured in the dogs by the usual method of relating the slowing of the heart to the transient pressure rise induced by the injections of phenylephrine. 3. We have shown that phenylephrine directly reduces the radius of the carotid sinus during the measurements of baroreflex sensitivity. At a dose of 2-4 micrograms/kg, phenylephrine has an enhancing effect on the baroreflex response, possibly resulting from a modification of baroreceptor output.

The effects of peripheral impedance and inotropic state on the power output of the left ventricle in dogs.

The power output of the left ventricle as measured by the product of the Fourier components of aortic pressure and aortic flow is linked by definition to the arterial impedance facing the heart as measured by the quotient of these components. Consequently, the use of power measurements to assess ventricular performance can be ambiguous when accompanied by afterload changes. The heart is considered to function normally between two extremes, a constant flow pump, and a constant constant pressure pump, and two power limits are defined from these. The power limits describe the extent to which impedance changes can affect the power delivered by the left ventricle. Measured power changes that are found to lie outside the two limits can be unambiguously ascribed to changes in inotropic state. The results from preliminary dog experiments designed to test this method are reported. Cardiac sympathetic stimulation and isoprenaline infusion were used to provide a pure inotropic stimulus and a mixture of inotropic and afterload changes, respectively. The technique was able to detect inotropic changes in the heart even in the presence of simultaneous changes in afterload. Eight conventional indices of cardiac performance were monitored for comparison. The extent of their afterload dependence may not be as easily quantified.

Continuous measurement of left ventricular volume using a single dimensional transducer: a comparison of two techniques in open chested dogs.

A comparison has been made of the continuous measurement of left ventricular volume in open chested dogs by two simple dimensional transducer systems: a mercury-in-rubber strain gauge measuring epicardial arc length at the ventricular equator and a pair of electromagnetically coupled coils placed on opposite sides of the left ventricle to measure its diameter. The single dimensional measurements were converted to volume measurements after death by filling an intraventricular ballon with known volumes of liquid. The strain gauge proved clearly superior to the coupled coils because it was not possible in practice to position the coils precisely facing each other and they did not remain tangential to the epicardial surface throughout the cardiac cycle. A single epicardial strain gauge can provide sufficiently accurate measurements of left ventricular volume to warrant its use in physiological studies of cardiac function. Although considerable attention to detail is required this technique has the advantages of being inexpensive and producing a continuous record which is easily interpreted.