1. Syncopal or near syncopal episodes have been observed in five subjects who stood or were tilted and in whom blood samples were being taken. 2. In all subjects bradycardia and hypotension developed before the onset of symptoms. Increases in plasma adrenaline concentrations occurred in all subjects, beginning before the faint. Changes in plasma noradrenaline concentrations were variable: in three subjects there was a marked fall and in the other two subjects an increase. Plasma vasopressin increased in all subjects. 3. Increases in plasma adrenaline may be contributing to the vasodilatation and arterial hypotension which occur during syncope.

1. We examined the acute effects of ethanol consumption on circulatory responses to the cold pressor test, to handgrip exercise and to intravenous infusion of methoxamine in eight normal male subjects. 2. Ethanol consumption reduced systolic blood pressure responses to the cold pressor test and to handgrip exercise and depressed both systolic and diastolic blood pressure responses to infusion of methoxamine. The depressant effects of ethanol on blood pressure responses to methoxamine were considerably greater than the effects on the cold pressor test and handgrip exercise. Catecholamine concentrations during the cold pressor test and handgrip exercise were not significantly different with or without prior ethanol consumption. 3. Alcohol has been shown to have an acute hypotensive action with all the stimuli.

1. Respiration during sleep was studied in 16 withdrawn alcoholic patients and in 12 control subjects. 2. The alcoholic patients had increased numbers of central ( P < 0.01) and of obstructive ( P < 0.05) apnoea and of hypopnoea episodes ( P < 0.01) as compared with controls. 3. Significant positive associations were found between the frequencies of central apnoea ( P < 0.05) or hypopnoea ( P < 0.01) and clinical evidence of central nervous system damage in the alcoholic patients. Hypopnoea also showed a significant association with vagal neuropathy ( P < 0.05), assessed by tests of cardioreflexes. 4. We conclude that abnormal respiratory events are common in abstinent alcoholic patients and that they are likely to be at least partly related to nervous damage.

1. Twenty-five normotensive men were subjected to two periods of mental stress involving a cognitive task and a competitive electronic game. Plasma catecholamines, heart rate and blood pressure were measured before and during mental stress. Responsiveness to β-adrenoceptor stimulation was also determined in each subject by measurement of heart rate responses to bolus injections of isoprenaline. 2. Both periods of mental stress were associated with significant increases in systolic and diastolic blood pressures, heart rate and plasma adrenaline, but not plasma noradrenaline. Heart rate responses to mental stress varied widely, with increases ranging from 1 to 48 (mean ± sd 13.5 ± 10.6) beats/min for the cognitive task and from 2 to 49 (20.4 ± 14.0) beats/min for the electronic game. Systolic blood pressure responses also varied widely and showed significant positive correlations with heart rate responses. 3. Significant relationships were found between heart rate responses to both forms of mental stress and cardiac sensitivity to isoprenaline, subjects with low responsiveness to β-adrenoceptor stimulation tending to have smaller heart rate responses to mental stress than subjects with high responsiveness to β-adrenoceptor stimulation. Relationships were also found between plasma adrenaline responses and heart rate responses to mental stress, although these did not reach significance. Considerably improved relationships were found when heart rate responses were correlated with a single variable generated from the product of the adrenaline response and the inverse of the dose of isoprenaline required to raise heart rate by 25 beats/min. 4. It is concluded that wide variation is shown between different individuals in responsiveness to β-adrenoceptor stimulation and that this is an important factor in the variability between individuals in heart rate and systolic blood pressure responses to mental stress. Both catecholamines and adrenoceptor-mediated responses to catecholamines should be examined when determining the physiological basis for differences in cardiovascular reactivity to mental stress between individuals or groups.

1. Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2–7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects. 2. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg. 3. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations. 4. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing. 5. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2–7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.

1. To investigate the stimulus to the cardiovascular and respiratory systems during isometric exercise, two patients with sensory neuropathies affecting forearm afferent nerves were studied and their circulatory and respiratory responses compared with those of normal subjects. The contribution of pain to the cardiorespiratory changes was also investigated in normal subjects by using hypnosis to relieve pain during and after isometric exercise. 2. The patients and normal subjects performed fatiguing isometric forearm exercises on a handgrip dynamometer on at least two occasions, once with normal forearm circulation and once with the forearm circulation occluded by an arterial cuff during and after exercise. Blood pressure, heart rate, minute ventilation, oxygen consumption and ventilatory equivalent were measured before, during and after exercise. 3. During exercises with and without occlusion increases in blood pressure and heart rate in patients and in subjects under hypnosis were similar to those in control subjects. Changes in oxygen consumption were also similar to those of controls, but the patients showed a smaller rise in ventilation and no increase in ventilatory equivalent. 4. After exercise in normal subjects occlusion of the forearm circulation produced continued elevation of blood pressure and respiration. Blood pressure also remained elevated after exercise with occlusion in subjects under hypnosis, but not in patients with sensory loss. Respiration did not remain elevated in either subjects under hypnosis or patients. 5. The results suggest that cardiovascular and respiratory changes during isometric exercise can occur without involvement of muscle sensory nerves and that pain contributes substantially to the increase in respiration. Normal sensory innervation is apparently necessary only for maintenance of raised blood pressure after exercise with occlusion.

1. Blood pressure, heart rate and changes of plasma renin concentration (PRC) have been studied in nineteen patients with traumatic transection of the spinal cord, in relation to change of posture from supine to upright. 2. When supine, subjects with cervical-cord transection had a normal blood pressure, a low heart rate and a high plasma renin concentration. On change of posture to the vertical, orthostatic hypotension developed, heart rate rose and PRC increased. Orthostatic hypotension was not a feature with change of posture in patients with transection of the thoracic spinal cord and PRC rose to a much smaller extent. 3. It is concluded that release of renin on change of posture can occur in patients with spinal-cord transection. Release of renin in man does not depend therefore upon an intact autonomic nervous system, though it is possible that reflex sympathetic pathways in the isolated spinal cord may be involved.

1. Seven patients with acromegaly and nine controls were studied before, during and after 30 min of moderate steady exercise on a bicycle ergometer. Venous blood samples were taken for estimation of growth hormone (HGH), immunoreactive insulin (IRI), pyruvate, lactate, glucose, free fatty acids (FFA), glycerol and ketone bodies. 2. Exercise caused a rise in HGH concentrations in the acromegalic patients, despite their pituitary tumour, and also in control subjects. Concentrations of IRI fell during exercise in control subjects, but rose in the acromegalic patients. 3. Concentrations of glycerol, FFA and ketone bodies rose rapidly to a maximum during exercise in the acromegalics and appeared to be suppressed before the end of exercise: there was no increase in the concentration of ketone bodies after exercise. In control subjects there was a gradual increase in glycerol and FFA concentrations towards the end of exercise, but no change in ketone bodies occurred until the post-exercise period, when ketone-body concentrations rose. 4. We conclude that exercise causes remarkable differences in metabolite concentrations in the blood of acromegalic patients compared with controls, with the concentration of fat metabolites reaching a maximum, then decreasing during the period of constant exercise. There was also elevation, instead of the normal fall, of plasma IRI activity and it is suggested that the decreased concentration of fat metabolites occurred because of the change of insulin concentration. It is further suggested that in acromegaly insulin retains its effect on re-esterification of fat in spite of resistance to its effects on carbohydrate metabolism.

1. The changes of peripheral venous plasma renin concentration (PRC) induced by head-up tilting were studied in four patients with orthostatic hypotension. 2. Two of the patients had the Holmes—Adie syndrome and tests of autonomic function suggested that they had an afferent block from baroreceptors with intact efferent pathways; the others had no evidence of the Holmes—Adie syndrome and investigations suggested that they had interruption of efferent sympathetic pathways. 3. In the two patients in whom lesions of the afferent side of baroreceptor reflexes were suspected, a marked increase in PRC occurred with upright tilting, whereas no change in PRC occurred in the two patients thought to have an efferent sympathetic block. 4. During repeated tilting, supine blood pressure and PRC increased progressively in the two patients with suspected afferent block, but not in the two patients with suspected efferent block. 5. It is suggested that an increase in plasma renin may contribute to the supine hypertension sometimes observed in patients with orthostatic hypotension. 6. It is also suggested that renin release does not require intact autonomic reflexes although certain components of efferent sympathetic pathways, not dependent on baroreceptor reflexes, may be important.

1. Six patients with panhypopituitarism and eight controls were studied before, during and after 30 min of moderate, steady exercise on a bicycle ergometer. Venous blood samples were taken for estimation of growth hormone, pyruvate, lactate, glucose, FFA, glycerol and ketone bodies. 2. Exercise caused a rise in serum growth hormone levels in control subjects and these fell to pre-exercise levels within 90 min. There was no change in the levels in the patients. The patients showed changes in blood metabolites resembling those of the controls. FFA levels were considerably elevated and post-exercise ketosis developed, these changes being more marked in the patients. 3. The differences in FFA and ketone bodies between patients and controls may be due to the lower levels of fitness in the patients. A further explanation may be that growth hormone depresses FFA levels after initial mobilization during exercise in normal subjects, but no such action can occur in patients with hypopituitarism. 4. It is concluded that growth hormone does not necessarily have a major role in fat mobilization or in the production of post-exercise ketosis. Thus, the lower levels of ketosis observed in athletes are not due to their lower levels of growth hormone.