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Biomedical subjects

C J Mathias

Publications and source records attributed to C J Mathias.

At least 271 records · Page 15Linked to original sources

Renin release during head-up tilt occurs independently of sympathetic nervous activity in tetraplegic man.

1. The role of the sympathetic nervous system in the release of renin during head-up tilt has been studied in five normal subjects and in four tetraplegic patients with cervical spinal-cord transection above the sympathetic outflow. Blood pressure, heart rate and concentrations of plasma noradrenaline, plasma adrenaline and plasma renin activity were measured during head-up tilt to 45 degrees before and after acute beta-adrenoreceptor blockade with intravenous propranolol. 2. In the normal subjects there were minimal changes in blood pressure during head-up tilt and there was a rise in both plasma noradrenaline concentration and plasma renin activity. After propranolol values of plasma renin activity at rest fell with little change occurring during head-up tilt. 3. In the tetraplegic patients there was a substantial fall in blood pressure during head-up tilt. Concentrations of plasma noradrenaline and adrenaline did not change but there was a marked increase in plasma renin activity. Values of plasma renin activity both at rest and during head-up tilt were unaffected by propranolol. 4. We conclude that in tetraplegic patients renin release during head-up tilt may occur independently of sympathetic nervous activity and is probably largely dependent on activation of renal vascular receptors.

Adult↗

Hypokalaemic hyperchloraemic metabolic acidosis and vesical stone complicating appendicovesical fistulae.

Two patients with appendicovesical fistulae are described. Both presented with gastrointestinal and urinary symptoms. Biochemical examination showed hypokalaemic hyperchloraemic metabolic acidosis; radiographic investigations showed a vesical stone and a communication between the bladder and the bowel. The findings at operation suggested that the fistulae may have arisen as complications of previous appendicitis. The diagnosis of appendicovesical fistulae may be difficult but should be considered in the presence of hypokalaemic hyperchloraemic metabolic acidosis and vesical stones.

Acidosis↗

Physiological responses to insulin hypoglycaemia in spinal man.

The physiologically responses to hypoglycaemia induced by fish insulin were studied in nine tetraplegic subjects with physiological complete cervical spinal cord transection between C4 and C8. During hypoglycaemia there was a reduction in both systolic and diastolic blood pressure unlike in normal subjects. This was accompanied by a rise in heart rate. The normal rise in plasma adrenaline levels did not occur. Plasma human insulin levels were suppressed. The usual neuroglycopenic symptoms accompanying hypoglycaemia did not occur in the tetraplegics.

Adult↗

Antihypertensive effects of clonidine in tetraplegic subjects devoid of central sympathetic control.

1. The effects of 300 microgram of oral clonidine on blood pressure, heart rate, plasma noradrenaline and adrenaline concentrations were studied in seven tetraplegic subjects with physiologically complete cervical spinal cord transections. 2. Clonidine did not significantly change resting blood pressure during the 8 h of the study. Resting heart rate fell. Resting plasma noradrenaline and adrenaline concentrations, when measured 2 h after clonidine, were not significantly lower. 3. Urinary bladder stimulation resulted in a marked rise in blood pressure accompanied by an elevation in plasma noradrenaline but not adrenaline. The hypertensive response to bladder stimulation was substantially reduced by clonidine, the maximum suppression occurring 2-4 h after administration of the drug. The plasma noradrenaline response to bladder stimulation, when measured 2 h after clonidine, was significantly lower than the response before clonidine. In two tetraplegic subjects with indwelling catheters the rise in intravesical pressure caused by bladder stimulation was unchanged by clonidine. 4. The pressor response to intravenous noradrenaline in two tetraplegic subjects and to intravenous phenylephrine in a further two tetraplegic subjects was unchanged by clonidine. 5. Clonidine may have additional antihypertensive effects which occur independently of actions in the brain. These effects may be exerted by an action either on sympathetic neurones in the spinal cord or on presynaptic alpha-adrenoreceptors in the periphery.

Adult↗

Indium-III: a new radionuclide label for studying human platelet kinetics.

Indium-III. when complexed with 8-hydroxyquinoline (oxine), has been employed as a radioactive platelet label for thrombus imaging in animals and man. The short half-life (2.8 d) and high yield of gamma photons of 111In make it ideal for in vitro counting and external imaging. To evaluate its suitability for studies of platelet turnover in man, platelet kinetic studies were carried out on 10 healthy volunteers using 111In-and 51Cr-platelets concurrently. For 111In labelling, platelets were harvested by differential centrifugation from 43 ml of whole blood drawn into acid-citrate dextrose (ACD) solution. The platelets were washed and suspended in a mixture of ACD and isotonic saline and then incubated with 111In-oxine, rewashed, and suspended in plasma for reinfusion. 51Cr labelling was performed using standard methods. Mean labelling efficiency was 73% with 111In and 6.5% with 51Cr. In vitro studies demonstrated minimal release, elution, and reutilization of the 111In label. There was no significant difference in the aggregation response of 111In- and 51Cr-platelets to ADP and collagen. The in vivo recovery of 111In-platelets was approximately 50% greater than that of 51Cr-platelets whereas the platelet life spans were similar. These results indicate that 111In labelled platelets may be useful for thromobokinetic studies in man. The new method offers the advantages of reduced blood requirements, higher labelling efficiency, and the ability to perform external imaging of platelet distribution in vivo.

Adult↗

Cardiovascular control in recently injured tetraplegics in spinal shock.

Cardiovascular control was studied in five tetraplegic patients with physiologically complete cervical spinal cord transections. All had been injured less than two weeks previously and were in spinal shock. Blood pressure, heart rate, and plasma noradrenaline and adrenaline were measured at rest and during and after bladder stimulation and application of cold stimuli to skin below the level of the lesion. In three patients the cardiovascular responses to intravenously infused 1-noradrenaline and to the Valsalva manoeuvre were recorded. Measurements were also made in six chronic tetraplegic patients (in whom reflex spinal cord activity had returned) at rest, and during and after bladder stimulation, and in six normal subjects at rest. Average resting blood pressure in the recently injured tetraplegics was 130/57 (mean 81) mmHg, in the chronic tetraplegics 107/55 (mean 73) mmHg and in normal subjects 122/82 (mean 95) mmHg. Average resting heart rate was 64, 73 and 77 beats/min in the three groups respectively. Resting plasma noradrenaline and adrenaline levels in both the recently injured and chronic tetraplegics were lower than than in normal subjects. In the recently injured tetraplegics bladder stimulation caused minimal changes in blood pressure, heart rate and plasma noradrenaline and adrenaline levels. In the chronic tetraplegics similar stimulation caused marked hypertension, bradycardia and elevation in plasma noradrenaline but not adrenaline levels. Cold stimuli in the recently injured tetraplegics did not change blood pressure or heart rate. In the recently injured tetraplegics intravenous infusion of 1-noradrenaline resulted in greater elevation in blood pressure than normal. There was a decrease in heart rate. One patient was able to perform the Valsalva manoeuvre. His blood pressure responses were consistenly abnormal ('blocked' Valsalva).

Adolescent↗

Scintigraphic detection of atherosclerotic lesions and venous thrombi in man by indium-111-labelled autologous platelets.

Accumulation of autologous platelets labelled with indium-111 at sites of atherosclerosis or venous thrombosis was demonstrated by scintigraphy in three patients. The lesions detected were bilateral ulcerated carotid-artery plaques, iliofemoral venous thrombosis, and renal-vein thrombosis. This technique shows promose as a non-invasive means of diagnosing focal atherosclerotic and thrombotic lesions.

Arteriosclerosis↗

The central hypotensive effect of clonidine. Studies in tetraplegic subjects.

A single oral dose of 300 microng of clonidine lowered systolic blood pressure by 20 +/- 4 mm Hg and diastolic blood pressure by 13 +/- 4 mm Hg in five healthy normotensive subjects (controls). Heart rate fell from 56 +/- 2 to 52 +/- 2 beats/min. In six tetraplegic subjects with physiologically complete chronic cervical spinal cord transection above the level of the sympathetic outflow, the same dose of clonidine did not significantly lower either systolic or diastolic blood pressure. Heart rate fell from 67 +/- 4 to 53 +/- 2 beats/min. Peak plasma concentrations of clonidine, measured by mass fragmentography, and elimination of the drug from plasma were similar in tetraplegic and control subjects and there was no difference in the incidence of the principal side effects of clonidine--sedation and dry mouth. Although the number of subjects studied is small, the absence of a fall in blood pressure after clonidine in the tetraplegic subjects suggests that the hypotensive action of clonidine in man is dependent on intact descending bulbospinal pathways and is mediated by withdrawal of sympathetic tone and provides direct evidence that some antihypertensive drugs may lower blood pressure in man by a direct action on the brain.

Adult↗

Postural changes in plasma renin activity and responses to vasoactive drugs in a case of Shy-Drager syndrome.

A male aged 47 years with gross autonomic insufficiency as part of the Shy-Drager syndrome is described. He did not sweat normally when warmed, and his circulatory responses to mental arithmetic, the Valsalva manoeuvre, and head-up tilt were abnormal indicating severe sympathetic failure. During head-up tilt there was a rise in plasma renin activity and plasma aldosterone. It is argued that plasma renin activity is not dependent on sympathetic nervous activity and may be mediated by renal baroreceptors. These rises may help sustain the blood pressure in such patients during repeated head-up tilts. Infusions of L-noradrenaline and angiotension produced greater hypertension, and injections of isoprenaline greater hypotension than in controls. Although it is difficult to exclude the possibility that one factor in this may be hypersensitivity of receptors in blood vessel walls, the principal factor is likely to be the absence of those baroreflexes of which the efferent pathways are in the sympathetic nervous system.

Angiotensin II↗

Plasma and urinary dopamine: studies during fasting and exercise and in tetraplegic man.

Dopamine, noradrenaline and adrenaline were measured in plasma and in urine, using double-isotope derivative techniques, in 46 normal subjects and in 17 tetraplegic patients with physiologically complete cervical spinal cord transections above the sympathetic outflow. Dopamine was present in plasma in normal subjects in a concentration of 0.33 mug/l +/- 0.06 (SEM). Twenty-four hour urinary excretion of dopamine averaged 248 mug +/- 22. There was a significant correlation between the 24 h urinary excretion of dopamine and of noradrenaline. In the normal subjects plasma dopamine and the urinary excretion of dopamine did not change during three days of fasting while urinary excretion of adrenaline increased twofold. In the normal subjects exercise significantly increased plasma dopamine from 0.25 mug/l to 0.43 mug/l, but significantly decreased the urinary excretion of dopamine. Exercise significantly increased the excretion of noradrenaline. In the tetraplegic patients the plasma dopamine concentration and the urinary excretion of dopamine were lower but not significantly different from the corresponding values in the normal subjects. Plasma noradrenaline and the urinary excretion of noradrenaline and adrenaline were significantly lower in the tetraplegic patients. It is concluded that dopamine is present in human plasma in concentrations similar to that of noradrenaline. Free dopamine in plasma and urine of normal subjects is not dependent on foot intake. Urinary dopamine may be derived from circulating dopamine. Urinary dopamine does not necessarily appear to reflect changes in plasma dopamine. The relationship between plasma dopamine and changes in adrenergic nervous activity deserves further investigation.

Adult↗

Bradycardia and cardiac arrest during tracheal suction--mechanisms in tetraplegic patients.

The cardiovascular responses to tracheal suction were observed in 4 consecutive recently-injured tetraplegics with physiologically complete cervical spinal cord transections (C3-5) who were in spinal shock and needed artificial ventilation. In all 4 patients tracheal suction induced bradycardia and in 2 patients even cardiac arrest. The bradycardia occurred when the patients were hypoxic, and was prevented by the addition of oxygen to inspired air, or, if this was inadequate, by the administration of atropine. Two of the patients were agains studied several months later, after return of isolated spinal cord activity and spontaneous breathing. In both patients tracheal suction then caused tachycardia and increased respiratory effort. It is concluded that: 1. Tetraplegics with high cervical spinal cord transections who are in spinal shock and unable to breathe spontaneously are prone to bradycardia and cardiac arrest during tracheal suction. This is more likely to occur when they are hypoxic. 2. The bradycardia appears to be due to a vago-vagal reflex for both afferent and efferent limbs of the arc are in the vagus nerve. A number of factors play a part, including (I) absent sympathetic activity; (II) airway receptor stimulation; (III) hypoxia and (IV) the inability to breathe spontaneously (The pulmonary (inflation) vagal reflex which would normally oppose the cardio-inhibition caused by (II) and (III) is absent). 3. The bradycardia in response to tracheal suction can be prevented by adequate oxygenation, or if this cannot be achieved, by repeated atropine.

Adolescent↗

Enhanced pressor response to noradrenaline in patients with cervical spinal cord transection.

Arterial blood pressure, heart-rate and the electrocardiogram were recorded in subjects tetraplegic from cervical spinal cord transections, and in control subjects, before, during and after intravenous infusions of 1-noradrenaline. Over a wide range of doses the blood pressure rose much more in the tetraplegics than in the controls. Circulating noradrenaline during infusion did not significantly differ between the two groups. The findings indicate that tetraplegic subjects have an enhanced pressor response to noradrenaline infusions. Such a response therefore does not necessarily indicate post-ganglionic sympathetic denervation. The observed responses in the tetraplegics may in part be due to exaggerated adrenergic receptor responses, but the main cause is likely to be the loss of those baroreceptor reflexes with sympathetic efferent pathways.

Adult↗

Dopamine beta-hydroxylase release during hypertension from sympathetic nervous overactivity in man.

In subjects with cervical spinal cord transections, hypertension due to sympathetic nervous overactivity resulted in a rise in plasma dopamine beta-hydroxylase (DbetaH), the peak occurring 3 to 5 min after the peak blood pressure response. This indicates that DbetaH may be released from sympathetic nerve terminals during sympathetic activity in man, and emphasizes the importance of sample timing in acute studies on DbetaH.

Adult↗

Plasma catecholamines during paroxysmal neurogenic hypertension in quadriplegic man.

Blood pressure, heart rate, and plasma catecholamine levels were measured in 16 quadriplegic subjects with physiologically complete cervical spinal cord transections above the level of the sympathetic outflow, and in 15 normal subjects (controls). In the quadriplegics the average resting blood pressure was 107/59 (mean, 75) mmHg, heart rate was 65 beats/min, and plasma norepinephrine (NE) and epinephrine (E) levels were 0.05 and 0.005 ng/ml, respectively. In the controls average resting blood pressure was 117/79 (mean, 92) mmHg, heart rate was 61 beats/min, and resting plasma NE and E levels were 0.20 and 0.06 ng/ml, respectively. Resting blood pressure and plasma NE and E levels were significantly lower in the quadriplegics (P less than 0.01, less than 0.001, less than 0.001, and less than 0.001, less than 0.001, respectively) than in the controls. In the quadriplegics, neurogenic hypertension was induced by bladder and muscle stimulation. This resulted in a marked elevation of both systolic and diastolic blood pressure (from an average of 109/60 (mean, 75) to 168/87 (mean, 114) mmHg) as a result of uninhibited sympathetic nervous activity through the isolated spinal cord. Plasma NE consistently rose, from an average of 0.05 to 0.16 ng/ml (P less than 0.001). There was significant linear relationship between plasma NE and mean blood pressure (P less than 0.001). In the quadriplegics infusion of l-norepinephrine to raise the blood pressure to comparable levels (from 105/58 (mean, 74) to 183/93 (mean, 123) mmHg) resulted in plasma NE levels approximately 21 times higher than during muscle and bladder stimulation. It is possible that the lower resting arterial blood pressure and plasma NE and E levels in the quadriplegics in comparison to normal subjects may reflect diminished resting sympathetic nervous activity. The rise in blood pressure following increased sympathetic nervous activity was accompanied by an elevation in plasma NE. The hypertension was not secondary to the rise in plasma NE. Plasma NE in these subjects appears to be a reliable index of prevailing sympathetic nervous activity.

Adult↗

Mechanisms of reflex cardiac arrest in tetraplegic patients.

Four patients with physiologically complete high cervical spinal-cord lesions, sustained within the previous 6 weeks, were observed. All needed intermittent positive-pressure ventilation. In the stage of spinal shock, stimuli to the trachea induced bradycardia, and in two patients cardiac arrest resulted. The bradycardia occurred when the patients were hypoxic, and seemed to be due to a vaso-vagal reflex. Normally this reflex is opposed by sympathetic activity, and during hypoxia by increased pulmonary (inflation) vagal reflex activity due to increased breathing. In these patients, however, compensatory sympathetic activity was prevented by the cervical cord lesion, and increased pulmonary vagal reflex activity by the fact that the breathing was artificial and therefore did not increase with hypoxia. Treatment in emergency includes the administration of atropine. Adequate oxygenation and, if this cannot be achieved, maintenance atropin should prevent the bradycardia and cardiac arrest associated with stimulation of the trachea in artificially ventilated tetraplegic patients.

Adolescent↗

Circulatory reflexes in tetraplegics during artifical ventilation and general anaesthesia.

The arterial blood pressure, heart rate and electrocardiograph were recorded, and plasma electrolytes, arterial blood gases and pH, and plasma catecholamines were estimated in seven patients with physiologically complete cervical spinal cord transections who needed intermittent possitive pressure ventilation (I.P.P.V.) or were undergoing urological surgery under general anaesthesia. In the tetraplegics on I.P.P.V., bradycardia, and in two patients even cardiac arrest, occurred during tracheal suction, especially in the presence of hypoxia. In one tetraplegic being anaesthetised, cardiac arrest occurred during endotracheal intubation. This reflex bradycardia and cardiac arrest appeared to be due to a vago-vagal reflex, unopposed by sympathetic activity or by the pulmonary (inflation) vagal reflex. Atropine was effective in preventing this reflex. In the tetraplegics undergoing urological surgery, severe hypertension resulting from visceral stimulation was effectively reduced by halothane. In these patients, control of arterial blood pressure with lower concentrations of halothane may also be achieved with I.P.P.V.

Anesthesia, General↗