SUMMARY1. Under conditions where heart rate, mean aortic pressure and enddiastolic pressure in the left ventricle are held constant, the intravenous infusion of isoprenaline is accompanied by large changes in dP/dt max in the left ventricle.2. Under similar conditions, during stepwise increments in the rate of infusion of isoprenaline the changes in dP/dt max (measured at a constant paced heart rate) were proportional to changes in the free (intrinsic) heart rate. It is concluded that dP/dt max is a quantitative index of inotropic changes in the left ventricle.3. In comparison to dP/dt max, three other variables which have been used to indicate inotropic changes in the heart (peak pressure in the left ventricle, duration of systole and stroke work at constant end-diastolic pressure), were shown to be unreliable indices of inotropic changes.4. Using dP/dt max to indicate inotropic changes, alteration in the heart rate while mean aortic pressure and end-diastolic pressure in the left ventricle were held constant, and in mean aortic pressure while heart rate and end-diastolic pressure in the left ventricle were held constant, were each shown to be accompanied by small inotropic changes in the heart.5. Under similar conditions, changes in end-diastolic pressure in the left ventricle alone were not accompanied by inotropic changes as indicated by dP/dt max.

1 In a preparation in which cardiovascular reflexes were prevented from occurring, ICI 118,587 (1-(p-hydroxyphenoxy)-3-p-(morpholinocarbonamido) ethylamino-2-propranol fumarate) caused dose-dependent positive chronotropic and inotropic effects upon the dog heart. 2 The increase in heart rate brought about by ICI 118,587 was about 43% of the maximum increase produced by isoprenaline.3 For a given chronotropic effect produced by either ICI 118,587 or isoprenaline, each compound produced a similar inotropic effect as indicated by an increase in LV dp/dtmax. 4 In contrast to the direct stimulant action of ICI 118,587 on the heart no direct effects on vascular smooth muscle were observed.5 ICI 118,587 was shown to be a competitive antagonist of the chronotropic and vasodilator effects of isoprenaline on the heart and blood vessels and of the chronotropic effects of noradrenaline on the heart. 6 It is concluded that ICI 118,587 is a selective 1l-adrenoceptor partial agonist.

SUMMARY1. Distension of the atrial appendages resulted in a diuresis, an increase in the rate of Na+ excretion and an increase in heart rate.2. Both the urinary and heart rate responses to distension of the appendages were either abolished or much reduced by crushing the bases of the appendages.3. The diuresis in response to distension of the atrial appendages is similar to that previously described in response to distension of the pulmonary vein-atrial junctions by Ledsome & Linden (1968).4. It is concluded that stimulation of nerve endings within the atrial appendages results in a reflex increase in urine flow and heart rate.

SUMMARY1. Stimulation of left atrial receptors by distending balloons located at the junction between the pulmonary veins and the left atrium and in the body of the left atrium resulted in a diuresis in anaesthetized dogs.2. In the same dogs the diuresis was not consistently associated with a reduction in the antidiuretic activity of plasma as compared with that during the initial control period. The antidiuretic activity of dog plasma was assayed in water-loaded rats anaesthetized with ethanol.3. Intravenous injections of vasopressin suppressed a water diuresis in water-loaded dogs anaesthetized with chloralose. The changes in antidiuretic activity of dog plasma which resulted from these injections were reliably detected by the bio-assay in the rat.4. It is concluded that the diuretic response to the stimulation of left atrial receptors is not accompanied by a reduction in the plasma antidiuretic hormone level.

SUMMARY1. Localized distension of the junction between the superior vena cava and the right atrium without obstructing venous return caused an increase in heart rate.2. This increase in heart rate was a reflex response; the afferent path was in the vagi and the efferent solely in the sympathetic nerves.3. The receptors most likely to be stimulated by the distension of the junction between the superior vena cava and the right atrium are the right atrial receptors located on the endocardial surface of the intrapericardial portion of the superior vena caval-right atrial junction.

SUMMARY1. Stimulation of left atrial receptors, by distension of the pulmonary vein/left atrial junctions, is known to cause a reflex increase in heart rate; the efferent pathway is known to be solely in the sympathetic nerves.2. In expectation of a concomitant positive inotropic response the effect of stimulating the left atrial receptors on the inotropic state of the left ventricle was studied, using as a known sensitive index of inotropic changes the maximal rate of rise of pressure in the left ventricle (dP/dt max).3. Stimulation of left atrial receptors resulted in an increase in heart rate but there were no significant concomitant changes in dP/dt max.4. It is concluded that activity in this discrete efferent pathway does not include an inotropic effect on the left ventricle and therefore the reflex involves only those sympathetic nerves which innervate the sinu-atrial node.5. The possible function of atrial receptors in the regulation of heart volumes is discussed.

SUMMARY1. Action potentials were recorded from fibres in the right cervical vagus, the receptor endings of which were localized to the endocardial surface of the superior vena caval-right atrial junction.2. Stretching the junction between the superior vena cava and the right atrium without obstructing venous return caused an increase in the discharge of these fibres. This increase in impulse frequency was similar to that caused by small changes in mean right atrial pressure (range 0-13-5 cm H20).3. This evidence supports the earlier suggestion that stimulation of the right atrial receptors by stretching the superior vena caval-right atrial junction causes a reflex increase in heart rate.

1. The existing methods for assessing states of acidosis are discussed with particular reference to non-respiratory acidosis. Most of these methods are based either on the Henderson-Hasselbalch equation or on the direct extrapolation of in vitro studies on blood to the whole animal. The evidence available shows that these methods cannot be used to obtain an accurate assessment of disturbances of acid-base balance in the whole animal.2. The experiments were designed to investigate the acid-base parameters of an animal when a respiratory acidosis was superimposed on a non-respiratory acidosis caused by the infusion of N HC1; from these experiments it was possible to construct COz titration curves at various levels of non-respiratory acidosis. 3.A scheme which is based upon the C02 titration curves, has been proposed for assessing an acute acid-base disturbance in terms of its respiratory and non-respiratory components.4. The use of sodium bicarbonate to correct a non-respiratory acidosis was investigated, and it was shown that the amount of sodium bicarbonate required varied with the rate of infusion. No firm predictions could be made regarding the dose of bicarbonate required, but from the results of the present experiments an infusion rate of 0.1 mEq kgg' min-' is recommended in dogs. I N T R O D U C T I O NAcid-base balance is an aspect of physiology which has engaged the attention of biochemists, clinicians and physiologists. Unfortunately due to defects in communication between these disciplines there has been a considerable degree of confusion over both the terminology and the concepts involved.A basic difficulty is that it is not possible to measure either the hydrogen ion concentration or its activity in physiological fluids. The pH numbers provided by electrometric measurements Correspondence : Professor R. J. Linden,