Instantaneous and steady-state pressure-flow relations of the coronary system in the canine beating heart.

Steady-state and instantaneous pressure-flow relations were both obtained from the pump-perfused left coronary bed of the beating heart in seven mongrel dogs. The steady-state pressure-flow relation was obtained by changing flow, and measuring pressure after it reached a steady level; it showed a sigmoid shape, with flow-regulation around 70 ml . min-1 . 100 g-1, and it had an average zero-flow pressure intercept of 1.9 kPa (14 mmHg). This curve was represented by an equation, using four parameters. The quality of regulation of the coronary bed could be quantified with this equation by determining the pressure range, when flow was changed from 25% below to 25% above control level. We found this pressure range to be 8.7 +/- 2.4 kPa (65 +/- 18 mmHg) on the average. The tangent at each point of steady-state pressure-flow relation was called differential resistance. Instantaneous pressure-flow relations were obtained by superimposing stepwise changes of flow of different amplitude, at several steady-state levels of flow. Pressure followed these steps with a time-constant of 0.3 +/- 0.1 s, due to capacitive effects, then remained constant during 3 to 4 s, and thereafter changed due to regulation. Pressure was measured during the plateau, assuming it to be a regulation-free period. The instantaneous pressure-flow relations were found to be linear, and the slope was called instantaneous resistance. In the physiological range of flows, instantaneous resistance increased with flow. The ratio between instantaneous and differential resistance, the regulatory index, is suggested to quantify regulation at each point of the steady-state curve. This index was between one and zero up to the upper limit of the regulatory range; at higher flows it was negative. In the maximally vasodilated bed the instantaneous pressure-flow relations fell along the steady-state relation, and the regulatory index was thus equal to zero at all flow-levels.

Coronary input impedance during cardiac cycle as determined by impulse response method.

The coronary arterial system was characterized by its input impedance determined in systole and diastole from impulse response functions in five dogs. The impulse response technique was verified on a known hydraulic system. A second confirmation was obtained on the circumflex artery: reflected pulses were correlated with site of reflections generated by occlusions. The impulse response indicates discrete reflections, superimposed on the tail of the response, resulting from diffuse reflections. Input impedance was calculated from Fourier analysis of the impulse response. Characteristic impedance was 1.0 +/- 0.2 X 10(9) Pa X s X m-3 (0.13 +/- 0.02 mmHg X ml-1 X min) and impedance at 0 Hz was 2.6 +/- 0.8 X 10(9) Pa X s X m-3. No significant differences between systole and diastole were found in both characteristic impedance and impedance at 0 Hz. It is concluded that the coronary system consists of a proximal part that can be described with the three-element windkessel and a distal part not seen by oscillatory pressure or flow perturbations, which depends on the phase of cardiac contraction.

Effect of carbenoxolone on the synthesis of glycoproteins and DNA in rat gastric epithelial cells.

The influence of carbenoxolone on the synthesis of glycoproteins in the surface mucous cells and the production of new cells in the rat gastric mucosa was studied by means of a vascular perfusion system. The rate of incorporation of tritiated galactose, glucosamine, serine, and sulphate in surface mucous cells, studied by autoradiography, was not affected by the addition of carbenoxolone to the drinking water. The sugar composition (determined by gas-liquid chromatography) of the gastric glycoproteins (isolated by centrifugation in CsCl), was not changed in carbenoxolone-treated rats. Compared with untreated animals, the number of [3H]-thymidine labelled nuclei per fundic pit increased by 38% to 76% in carbenoxolone-treated rats, implying a higher number of mitotically active cells. This results in an increased supply of young mucous cells; if this also proves to be true in human gastric mucosa, it may be relevant to the therapeutic effect of carbenoxolone.

Vascular perfusion of the isolated rat stomach with a fluorocarbon emulsion.

A constant-pressure system using a fluorocarbon (FC-75) containing artificial medium was used for vascular perfusion of the isolated rat stomach. A 10% emulsion of FC-75 in a modified Tyrode solution, containing 3.5% bovine serum albumin, amino acids, nucleosides, and beta-hydroxybutyrate appeared to allow an adequate perfusion for at least seven hours. The following criteria were used to estimate for functional state of the perfused stomach: (1) venous flow, (2) oxygen consumption, (3) leakage from the blood vessels to the gastric lumen, (4) ultrastructure, (5) secretion of H+ and pepsinogen after stimulation, and (6) transport of labelled macromolecules. During perfusion oxygen consumption and venous flow remained, after an initial high value, constant for at least seven hours. Leakage from the vascular bed was absent. Ultrastructure was preserved for at least seven hours. Administration of pilocarpine led to secretion of HCl ad pepsinogen. Pentagastrin and histamine stimulated HCl secretion in only some of the preparations. [3H]-galactose was incorporated into macromolecules and transported from the Golgi-region towards the apex of the cell. These observations led to the conclusion that the described vascular perfusion system in at least an appropriate model for studying glycoprotein synthesis.

Glycoprotein synthesis in the mucous cells of the vascularly perfused rat stomach. I. Surface mucous cells.

We developed a constant-pressure vascular perfusion system of the isolated rat stomach, utilizing an artificial, fluorocarbon (FC-75)-containing medium. Perfusion could be maintained for at least six hours, as demonstrated by the ultrastructure of the mucosal cells and by the constant incorporation of [3H]-galactose in the surface mucous cells. Moreover all mucous cell types in tissue fixed after six hours of perfusion showed the same histochemical reactions for glycoproteins as in tissue fixed shortly after decapitation of the animal. The surface mucous cells of the antrum incorporated 30% less [3H]-galactose, [3H]-serine and [35S]-sulphate than those of the fundus. The amount of radioactivity incorporated per cell did not decrease during a subsequent 2 hour chase.

Identification of canine coronary resistance and intramyocardial compliance on the basis of the waterfall model.

This study was performed to elucidate the effects of cardiac contraction on coronary pressure-flow relations. On the basis of the waterfall mechanism, a lumped model of the coronary arterial system is presented consisting of a proximal (epicardial) compliance, a coronary resistance, and an intramyocardial compliance. A "back"-pressure, assumed to be proportional (constant k) to left ventricular pressure, impedes flow. From steady-state measurements of circumflex coronary artery flow and inflow pressure, together with left ventricular pressure, the values of the three model parameters and the constant k have been estimated. In the control condition proximal compliance is found to be 1.7 X 10(-12) m4s2kg-1, intramyocardial compliance 110 X 10(-12)m4s2kg-1, and resistance 7.5 X 10(9) kgm-4s-1. The proportionality constant k is close to unity. Effects of changes in left ventricular pressure and inflow pressure and the effect of vasoactive drugs on the parameters are also investigated. Changes in coronary resistance are always opposite to changes in intramyocardial compliance. Sensitivity analysis showed that epicardial compliance plays its major role during isovolumic contraction and relaxation; resistance plays a role throughout the cardiac cycle but is more important in diastole than in systole, whereas intramyocardial compliance plays a role in systole and in early diastole.

Glycoprotein synthesis in the mucous cells of the vascularly perfused rat stomach. II. Differentiating mucous cells.

Labeled leucine, serine, galactose, glucosamine and sulphate were administered to rat stomachs in a perfusion system. Sections of the gastric fundus were studied by light microscopic autoradiography. Five categories of mucous cells were distinguished and their glycoprotein synthetic activity was measured in autoradiographs by counting silver grains over each category. During their differentiation, while migrating from the isthmus of the fundic glands to the free luminal surface, the surface mucous cells (SMC) showed an increase in incorporation of all precursors used. Differences between the incorporation patterns of the various precursors, in cells of different ages, suggest that structural development runs ahead of functional activity, and that the latter continues up to the very moment the cell is shed from the surface. Sulphate was incorporated at a considerably lower rate by the SMC of the free surface than by the foveolar SMC, in which by cytochemical staining strongly acidic glycoproteins were shown. Since the mucous neck cells incorporated all precursors at a low rate, these cells apparently do not play an important role in gastric mucus synthesis. They did not incorporate sulphate, which is consistent with histochemical observations.