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Local anaesthetic drugs were instilled into the pericardial sac of conscious rabbits through a chronically implanted catheter. Twenty mg of procaine HCl always caused complete blockade of cardiac vagal and sympathetic efferent nerves, tested by eliciting the baroreceptor-heart rate reflex, and abolished the reflex depression of renal sympathetic nerve activity elicited by impeding left ventricular outflow. It also slowed heart rate by a direct effect on the sinoatrial pacemaker. When the same dose of procaine was given intravenously there were only transient changes in blood pressure, heart rate and the baroreceptor-heart rate reflex. Lignocaine HCl and bupivacaine HCl were relatively less effective in blocking cardiac sympathetic efferent nerves. Intrapericardial procaine can be used in conscious animals to elucidate the part played by the cardiac receptor reflexes in control of the circulation.

We attempted to detect and quantify the mechanical effects of change in right atrial pressure on the chronotropic properties of the cardiac pacemaker, when blood volume was altered in an isohaemic fashion by +/- 27% in 8 conscious rabbits. Under control conditions there was a strong negative association between heart rate and right atrial pressure, attributable to the baroreceptor-heart rate reflex. After deletion of the main afferent sources of reflex effects on heart rate, by denervating the arterial baroreceptors and chemoreceptors, there was an insignificant association between heart rate and right atrial pressure or arterial pressure. Then, in addition, the main neurohumoral effects on the cardiac pacemaker were eliminated by three different pharmacologic treatments: (1) the cardiac nerves were blocked by instilling 2% procaine into the pericardial sac, (2) cardiac beta-adrenoceptors and cholinergic receptors were blocked with intravenous propranolol and hyoscine methyl bromide, (3) the above treatments were combined with autonomic ganglion-blockade by intravenous pentolinium. The combination of cardiac afferent and efferent blockade (1 and 3) revealed a small but consistent positive association between heart rate and right atrial pressure of 1.3 and 0.7 beats/min/mmHg, respectively. With efferent blockade alone (2), there was a steeper positive association of 2.3 beats/min/mmHg. We conclude that in the conscious rabbit there may be a mechanical effect of right atrial pressure on the cardiac pacemaker, but that it is so small as to be of little importance under physiological conditions.

The contributions of the sympathetic nervous system and the adrenal medullary catecholamines to the response of dog hind limb resistance vessels to haemorrhage were examined. Anaesthetized dogs were bled either 30% or 45% of blood volume. There was little difference between the vascular conductance response in untreated hind limbs and sympathectomized limbs. Conductance in limbs that had been both sympathectomized and alpha-adrenergically blocked with phenoxybenzamine was markedly above that of untreated limbs. Blood flow in both the untreated limbs and the sympathectomized limbs was closely similar to that predicted from the pressure-flow curve for the hind limbs obtained in non-bled dogs. Flow was higher than predicted in the limbs with combined sympathectomy and alpha-adrenergic blockade. It is concluded that the sympathetic nervous system exerted little vasoconstrictive influence after haemorrhage, but that circulatory catecholamines exerted a strong vasoconstrictive influence that was opposed in the normal limbs by an almost equally powerful vasodilatory force of undetermined origin.

We describe the use of a snare to denervate the carotid sinus in conscious rabbits whose other arterial baroreceptors had been denervated 8-14 days previously by surgical operation. Within 2 min of tightening the snare arterial blood pressure had risen from 81 +/- 2 to 119 +/- 5 mmHg, and heart rate had risen from 214 +/- 9 to 280 +/- 9 beats min-1. They remained at these high levels for 15 min but then fell, so that after 30 min blood pressure and heart rate were 103 +/- 9 mmHg and 265 +/- 8 beats min-1 respectively. They declined somewhat further, but irregularly, over the succeeding 7 days. The previously brisk baroreceptor-heart rate and carotid sinus reflexes were abolished by ensnaring the carotid sinus nerve, and remained absent over the succeeding 7 days. This method of deleting input from the arterial baroreceptors is not confounded by general anaesthesia or surgical injury, and allows observations to be made within minutes. The rapid decline in blood pressure and heart rate after 15 min, and the subsequent slow downward trend, are unexplained. They are of potential importance in experiments designed to quantitate the effects of baroreceptor input on the circulation. We also noted that, whereas spontaneous activities of the baroreceptor-intact rabbit were usually associated with transient rises of blood pressure and heart rate, after deletion of baroreceptor input the same activities were usually associated with transient falls.

This paper describes a method, using an interactive computer programme, for fitting a curve to data which is expected to assume a sigmoid form. The programme is specifically designed to generate best estimates of the limits and maximum slope of stimulus-response curves for the carotid sinus baroreceptor reflex, but is applicable to curve-fitting tasks in other fields such as immunology, pharmacology, biochemistry and neurophysiology.

This paper reports experiments to determine the relative roles of changes in cardiac output and systemic vascular resistance in determining the blood pressure response to intermittent step-changes and continuous sinusoidal changes in carotid sinus transmural pressure. Conscious rabbits with a variable-pressure capsule implanted around an innervated carotid sinus were used. After step-change in capsule pressure the approximate proportions of the changes in blood pressure attributable to changes in cardiac output were, during the pressor response, 7% after 2.5 s, 22% after 10 s and 27% at plateau, and during the depressor response 100%, 8% and 17%, respectively. During sinusoidal change in capsule pressure a mean 7% of the change in blood pressure over the full cycle was attributable to change in cardiac output.

By comparing the clearance rates of ICG and 99mTc-sulphur colloid from the blood stream, it has been possible to provide a method for assessing the phagocytic activity of the reticulo-endothelial system in man.