Mary J. Scott

The effects of stimulation of the carotid body chemoreceptors on heart rate in the dog

It is well known that hypoxia causes tachycardia, but there is no general agreement as to the mechanism of this effect. Some workers have assumed it to be the result of a reflex arising from stimulation of the carotid body and aortic arch chemoreceptors (Asmussen & Chiodi, 1941; von Euler & Liljestrand, 1942; Whitehorn, Edelmann & Hitchcock, 1946; Dripps & Comroe, 1947; Alveryd & Brody, 1948), despite there being a number of conflicting reports of the effects of stimulation of the chemoreceptors on heart rate. Stimulation of the carotid bodies by various drugs injected into the common carotid artery of spontaneously breathing dogs caused bradycardia (Heymans, Bouckaert & Dautrebande, 1931 a, b; Heymans, Bouckaert, von Euler & Dautrebande, 1932; Heymans, Bouckaert, Farber & Hsu, 1936; Comroe & Schmidt, 1938; Heymans & Bouckaert, 1941), but perfusion of the carotid sinus region using Ringers solution with either a high CO2 content or a low pH resulted in tachyeardia (Heymans, Bouckaert & Dautrebande, 1930; Heymans, Bouckaert & Samaan, 1935). More recently, Bernthal, Greene & Revzin (1951) excited the carotid bodies by hypoxic blood and found variable effects on heart rate. In every case chemoreceptor stimulation, whether by drugs, Ringers solution or hypoxic blood, caused reflex hyperpnoea. On the other hand, in dogs in which the rate and depth of respiration were controlled by a pump, stimulation of the carotid bodies by either hypoxic or venous blood invariably caused bradycardia (Bernthal et al. 1951; Daly & Daly, 1957). In the cat Landgren & Neil (1952) found that stimulation of chemoreceptors by local application of various drugs to the carotid bodies invariably caused hyperpnoea, hypertension and tachycardia. In subsequent experiments, in which carotid body perfusion techniques were used, Neil (1956) showed that the tachycardia which occurs in systemic hypoxia was not the result of stimulation of the carotid body chemoreceptors.

An analysis of the primary cardiovascular reflex effects of stimulation of the carotid body chemoreceptors in the dog

It has been shown previously that stimulation of the carotid body chemoreceptors in dogs breathing spontaneously causes variable changes in heart rate (Bernthal, Greene & Revzin, 1951; Daly & Scott, 1958, 1959, 1962). A detailed study revealed that the change in heart rate was dependent upon at least two mechanisms. The first of these is a primary cardiac reflex arising from the chemoreceptors themselves, which causes slowing of the heart. The other mechanism was identified as occurring secondarily to the concomitant reflex increase in respiratory minute volume and causes an increase in heart rate. This secondary effect is due, at least in part, to a stretch reflex from the lungs and to a lowering of the arterial blood PCO2, and may be excluded by maintaining pulmonary ventilation constant by means of a pump (Daly & Scott, 1958, 1959). When pulmonary ventilation is maintained constant in this way during chemoreceptor stimulation, the primary cardiac reflex response becomes apparent (Daly & Scott, 1958). The purpose ofthe present investigation was to discover the mechanisms by which the primary cardiac response was brought about and to make observations on the changes in vascular resistance resulting from stimulation of the carotid bodies. Our results have been reported briefly elsewhere (Daly & Scott, 1961, 1962).

The cardiovascular responses to stimulation of the carotid body chemoreceptors in the dog.

As far as we are aware there have been no previous reports in the literature concerning the effect of reflexes from the carotid body chemoreceptors on cardiac output. We have recently carried out such an investigation in the anaesthetized dog and in the first part of the paper the results obtained both in animals breathing spontaneously and ventilated artificially are described. Some of the mechanisms responsible for the observed cardiovascular responses in the two types of preparation were also studied, and these are described in subsequent sections of the paper. Some of our results have been reported briefly elsewhere (Daly & Scott, 1959, 1963).

The effects of acetylcholine on the volume and vascular resistance of the dog's spleen

In a previous study of the effects of anticholinesterases on the spleen, Scott (1957) found that tetraethylpyrophosphate (TEPP) caused a small increase in volume after denervation of the spleen combined with bilateral adrenalectomy. Whether this response was the result of accumulation of acetylcholine or of a direct action of TEPP was not ascertained because passive effects due to alterations in arterial and venous pressures could not be ruled out. Although the effects of acetylcholine on the spleen have been investigated previously by numerous workers, the results have been variable. In the dog, cat and rabbit intravenous injection of acetylcholine caused either a decrease in volume of the spleen (Ferguson, Ivy & Greengard, 1936), a decrease followed by an increase (Hunt, 1918; Gotsev, 1936) or only an increase in volume (Bacq & Fredericq, 1935). Hunt (1918) considered that the initial diminution in splenic volume produced by acetylcholine was a passive vascular effect due to the fall in systemic blood pressure, and that the subsequent increase in volume was due to a direct action of the drug on the muscular capsule of the spleen. In the view of Bacq & Fredericq (1935) the increase in volume of the spleen was due to vasodilatation within the organ. Studies on isolated strips of spleen in vitro indicate that acetylcholine causes contraction, not relaxation (Fredericq, 1929; Vairel, 1933; Saad, 1935; Ferguson et al. 1936). The interpretation of changes in volume of the spleen occurring as a result of intravenous injections of a drug is often difficult because, apart from a direct effect on the organ, there are a number of other mechanisms by which the response may be brought about. First, the observed change in volume may be passive through an alteration in either arterial or portal venous pressure. Secondly, it may be the result of nervous influences on the spleen either by an action of the drug on the nervous system or reflexly through a change in arterial blood pressure. Thus Farber (1936) showed

The heart rate responses to carotid body chemoreceptor stimulation in the cat

Recent work has shown in the dog that the cardiac responses to stimulation of the carotid body chemoreceptors depend on at least two mechanisms. The first is a direct, or primary, reflex from the carotid bodies themselves, causing slowing of the heart. This response is mediated through the vagus and sympathetic nerves (Bernthal, Greene & Revzin, 1951; Daly & Daly, 1957; Daly & Scott, 1958, 1962; Downing, Remensnyder & Mitchell, 1962). The second mechanism arises secondarily as a result of the concomitant reflex increase in pulmonary ventilation and causes an increase in heart rate. This secondary tachyeardia is due, at least in part, to an inflation reflex from the lungs and to a fall in arterial blood Pco2 (Daly & Scott, 1958, 1962, 1963b). In the spontaneously breathing dog, this secondary tachycardia is usually prepotent. When pulmonary ventilation is maintained constant artificially the secondary effect is excluded and the primary reflex bradycardia is invariably observed. Few studies have been made on the cat. Landgren & Neil (1952) stimulated the carotid bodies by means of locally applied drugs and observed a tachyeardia in both the spontaneously breathing and artificially ventilated cat. More recently, however, Joels & Neil (1963) have reported results of experiments in which the carotid bodies were stimulated by hypoxic or asphyxial Krebs-Henseleit solution; in these experiments a slowing of the heart was observed. The present experiments were carried out with a view to determining the exact nature of the cardiac responses in the cat during stimulation of the carotid body chemoreceptors by hypoxic blood under conditions of natural and controlled ventilation. The results have been reported briefly elsewhere (MacLeod & Scott, 1963).

The effects of hyperventilation on the reflex cardiac response from the carotid bodies in the cat

1. Cats were anaesthetized with chloralose and urethane, and ventilated by an artificial intermittent negative pressure applied to the thorax. The carotid body chemoreceptors were isolated and perfused with oxygenated blood. They were stimulated by substituting hypoxic blood obtained from a donor animal.