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Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 397 records · Page 22Linked to original sources

Effect of tyramine on myocardial catecholamine release in coronary heart disease.

The influence of tyramine on myocardial catecholamine release and on coronary blood flow has not previously been determined in man. Therefore, the effect of tyramine was measured on coronary and systemic hemodynamics and on norepinephrine (NE) and epinephrine levels in blood from the aorta and coronary sinus in 9 patients with coronary artery disease. Tyramine produced a striking increase in coronary sinus NE, from a baseline of 344 +/- 56 to a peak level of 1416 +/- 310 pg/ml (p less than 0.01) 2 minutes after tyramine. The increase in aortic NE was less striking, from 265 +/- 32 to 421 +/- 63 pg/ml (difference not significant). Therefore, the net release of NE from the heart was increased by tyramine from 12,007 +/- 393 to 139,357 +/- 46,156 pg/ml/min (p less than 0.03). There was no release of epinephrine across the coronary bed. There was a variable response of coronary blood flow and resistance after tyramine. Thus, the rich innervation of the heart by sympathetic nerve endings can result in marked NE release into the coronary sinus.

Adult↗

Shock. Diagnosis and management.

Recent investigations have underscored the great diversity in both the causes and manifestations of clinical shock. The emphasis has shifted toward more specific therapy when that has been possible. Pure vasoconstrictors have assumed a secondary therapeutic role, as volume replacement or expansion has become the initial management of shock. Agents, such as naloxone hydrochloride, corticosteroids, fructose diphosphate, amrinone and milrinone , and nonsteroidal antiinflammatory agents, while still experimental, offer improved understanding and management of the shock syndrome.

Blood Volume↗

Caffeine and hypertension.

The effect of prolonged caffeine administration on blood pressure in hypertensive subjects was assessed in a double-blind placebo-controlled study. Eighteen hypertensive subjects participated, nine of whom received placebo throughout the study and nine of whom received placebo during the first three days, caffeine during the subsequent seven days, and placebo during the final four days of the two-week study. Those who received caffeine were given 250 mg with meals three times daily. There were no untoward reactions in the course of the study, but one subject with unacceptably high blood pressures while receiving placebo had to be discharged from the study to resume antihypertensive therapy. Systolic blood pressure was immediately increased (9.2 +/- 3.4 mm Hg) within 15 minutes after the first dose of 250 mg of caffeine. On the first day of caffeine, systolic pressure was increased a mean of 7.3 +/- 4.0 mm Hg, but this was no longer significant after the initial day of caffeine administration. Diastolic pressure showed a trend toward increasing, but this never reached significance. The minor increases in plasma catecholamine levels and plasma renin activity were not significant on either a short- or long-term basis. After discontinuation of caffeine, no overshoot phenomena were observed. It is concluded that prolonged administration of caffeine is not associated with significant elevation in blood pressure, plasma catecholamine levels, or plasma renin activity in patients with borderline hypertension.

Adult↗

Horseradish peroxidase injection of physiologically characterized afferent and efferent neurones in the guinea pig spiral ganglion.

Single afferent and efferent neurones in the guinea pig spiral ganglion were injected with horseradish peroxidase. They could be recovered in subsequent histological processing and traced from the injection site in the ganglion to their final termination in the organ of Corti. All responsive primary afferents innervated the inner hair cells (58 neurones). One outer spiral fibre innervating the outer hair cells was recovered. This cell was non-spiking and unresponsive to acoustic stimulation. Neurones having properties previously attributed to cochlear efferents, terminated on the outer hair cells in regions of the cochlea consistent with their characteristic frequencies.

Animals↗

Increased vascular beta2-adrenoceptor responsiveness in autonomic dysfunction.

Responsiveness to the vasopressor, vasodepressor and chronotropic effects of several sympathomimetic amines was assessed in 12 patients with severe autonomic dysfunction and in 8 age-matched control subjects. The patients with autonomic dysfunction showed a profound increase in responsiveness to both isoproterenol and phenylephrine as compared with control subjects. The mean bolus dose of isoproterenol required to increase heart rate by 25 beats/min was 0.9 + 0.2 microgram in the patients and 5.4 + 2.1 micrograms in the control subjects. The dose of isoproterenol required to reduce mean blood pressure by 25 mm Hg was 0.3 + 0.2 and 5.2 + 1.8 micrograms, respectively. Thus, although there is a 6-fold increase in responsiveness to the chronotropic effect of isoproterenol in autonomic dysfunction, the responsiveness to the drug's depressor effect is increased 17-fold. This enhanced depressor sensitivity is quite marked, even with oral beta-adrenoceptor agonists. Beta-adrenoceptor agonists must be used with caution in conditions associated with autonomic dysfunction if dangerous hypotension is to be avoided.

Aged↗

Accuracy of tidal volume, lung volume, and flow measurements by inductance vest in COPD patients.

We analyzed the accuracy of the inductance vest in measuring several ventilatory parameters in five patients with chronic obstructive pulmonary disease (COPD). We assessed tidal volume (VT) accuracy at different respiratory frequencies in different lying body positions with different thoracic and abdominal contributions to breathing and the accuracy over a 4-h time span. Mean percent error was calculated without regard to direction of error. The mean error of vest VT estimation was 7.6% for all body positions studied and 5.6% for right and left lateral positions combined. Vest VT accuracy was unchanged after 4 h and with changes in thoracic and abdominal contributions to VT. The mean errors for inspiratory and expiratory times were 3.3 and 2.0%, respectively. Volume was differentiated to flow. For respiratory rates ranging from 12 to 30 breaths/min, the mean error of the vest and our differentiation circuit in duplicating peak flows measured at the mouth was 3.5%. The ability of the vest to estimate changes in end-expiratory position or functional residual capacity was not as good as with VT; the mean error was 30.7%. For estimation of VT, ventilatory timing, and airflow in COPD patients, the inductance vest performs well. For measurement of changes in lung volume, improvements in vest design need to be made.

Abdomen↗

Phagocytosis, in vivo, of immune complexes by dendritic cells in the lymph of sheep.

Although the occurrence of dendritic, macrophage-like cells in the peripheral lymph of sheep, pigs, rabbits, and man is well documented, the exact nature of these cells has become controversial. Generally, such cells tend not to adhere firmly to glass or exhibit phagocytosis in in vitro systems. However, when immunized sheep were given a subcutaneous injection of specific antigen (horseradish peroxidase), most of the macrophage-like cells in the lymph from the injection site could be shown by transmission electron microscopy to have engulfed the immune complexes that had been formed in the subcuticulum.

Animals↗

Leukocyte beta-receptor alterations in hypertensive subjects.

It has been suggested that beta-adrenergic responsiveness is reduced in hypertension. To evaluate a possible alteration in human beta-receptors that might account for diminished beta-adrenergic responsiveness, we studied leukocytes from hypertensive and normotensive subjects after an overnight rest supine, and then after being ambulatory, a maneuver that increases plasma catecholamines approximately twofold. In supine samples, beta-receptor affinity for the agonist isoproterenol was significantly reduced in hypertensives and was associated with a reduction in the proportion of beta-receptors binding agonist with a high affinity from 42 +/- 6% in normotensive subjects to 25 +/- 2% in hypertensives (P less than 0.05). Alterations in beta-adrenergic-mediated adenylate cyclase activity parallelled the differences seen in the beta-receptor affinity for agonist. In normotensive subjects, beta-receptor density and the proportion of receptors binding agonist with high affinity were reciprocally correlated with plasma catecholamines. However, in the hypertensive subjects these correlations were not evident. Thus, our data suggest an alteration in leukocyte beta-receptor interactions in hypertensive subjects, and may represent a generalized defect in beta-receptor function in hypertension.

Adenylyl Cyclases↗

The transfer of immune complexes from the lumen of the small intestine to the bloodstream in sucking rats.

The epithelial cells along the small intestine of the sucking rat display specific receptors for IgG. These permit the uptake and transcellular transport of IgG, usually presented in milk, from the gut to the bloodstream. Antigen already combined with IgG may also gain access to the bloodstream by this route, but no data exists to show whether this could be sufficient to immunize or to induce tolerance in the young rat to a future exposure to antigen. Monoclonal IgG1 antibody to horseradish peroxidase was used in order to quantitate such a transfer of antigen, using the electron microscope and also studies with radiolabelled antigen and/or antibody. It was found that much less intact antigen was transferred to the bloodstream than would have been calculated from the quantity of antibody transported. Also, IgG1 combined with antigen was more likely to be broken down intracellularly than free IgG1. This was compared with the transport across rat hepatocytes of monoclonal polymeric IgA anti-horseradish peroxidase. The transfer of polymeric IgA from blood to bile was the same whether or not the IgA was complexed with antigen. However, as for the IgG system, less antigen was transported intact into bile than might have been expected theoretically.

Animals↗

Catecholamine and cortisol responses to sufentanil-O2 and alfentanil-O2 anaesthesia during coronary artery surgery.

The effects of alfentanil-O2 and sufentanil-O2 anaesthesia on plasma catecholamines and cortisol were investigated in 32 patients undergoing coronary artery bypass grafting operations. After lorazepam-atropine premedication and pancuronium pretreatment, alfentanil was given to 16 patients at a rate of 3 mg.min-1 and sufentanil was given to 16 patients at 300 micrograms.min-1 until the patients were unconscious; at this time they were given succinylcholine and were intubated. After intubation an amount of alfentanil or sufentanil equal to the dose producing unconsciousness was infused over the next 30 min, at which time the operation began. Additional alfentanil or sufentanil were given whenever systolic arterial blood pressure increased more than 15 per cent of preanaesthetic values. Arterial blood samples were obtained for epinephrine, norepinephrine and cortisol assay and cardiovascular dynamics were recorded prior to anaesthetic induction, 5 min after tracheal intubation, immediately prior to and five min after incision, ten min after maximal sternal spread, just prior to beginning and after 30 and 60 min of bypass and at the end of operation. Cardiovascular dynamics were little changed throughout anaesthesia and operation. Plasma epinephrine and norepinephrine were not significantly changed until bypass. During bypass both hormones became increased and remained increased at the end of operation. Plasma cortisol decreased after incision and remained decreased until the end of operation. These data indicate that alfentanil-O2 and sufentanil-O2 anaesthesia produce similar changes in plasma catecholamines and cortisol as does fentanyl-O2 anaesthesia and hormonal effects are, therefore, not an explanation for any advantages the newer narcotics may have over fentanyl.

Adult↗

Arterial and coronary sinus catecholamines in the course of spontaneous coronary artery spasm.

We studied plasma catecholamine levels in 10 patients with frequent spontaneous episodes of coronary artery spasm to evaluate the role of the sympathetic nervous system. Peripheral venous norepinephrine in supine and upright postures, urinary excretion of catecholamines, and functional testing of the sympathetic nervous system did not differ from the same measurements in control subjects. Arterial and coronary sinus levels of norepinephrine and epinephrine drawn early in ischemia were not elevated over baseline; coronary sinus norepinephrine levels were higher than those in arterial samples and rose from 315 +/- 32 (pg/ml +/- SE) at the onset of ST elevation to 490 +/- 49 pg/ml late in ischemia (p less than 0.05). Plasma epinephrine levels, higher in arterial than coronary sinus samples, also rose significantly only late in ischemia, from 44 +/- 14 pg/ml to 148 +/- 35 pg/ml (p less than 0.05) in arterial blood and from 33 +/- 10 pg/ml to 108 +/- 29 pg/ml in coronary sinus samples (p less than 0.05). Generalized sympathetic nervous system activation is not likely to be the sole cause of coronary artery spasm.

Adult↗

Clonidine raises blood pressure in severe idiopathic orthostatic hypotension.

The hemodynamic effects of clonidine were studied in four patients with sever idiopathic orthostatic hypotension and one patient with baroreceptor dysfunction. No depressor response to clonidine was observed in any patient with idiopathic orthostatic hypotension at any dosage. Rather, two patients responded to 0.4 mg of oral clonidine with a 40 mm Hg increment in systolic blood pressure lasting several hours. Each has been receiving clonidine, 0.4 mg twice daily, for one year with greatly increased functional capacity. The other two patients with idiopathic orthostatic hypotension had an even greater pressor response to 0.8 mg of oral clonidine, but adverse effects prevented continued therapeutic use. In marked contrast, the patient with baroreceptor dysfunction had a profound depressor response to 0.2 mg of clonidine. In the treatment of idiopathic orthostatic hypotension, the major advantage of clonidine over other pressor agents is its longer duration of action. The major adverse effects of the drug in these patients are sedation, dry mouth, altered mentation, and excessive hypertension. The drug should not be given to patients with mild idiopathic orthostatic hypotension or selective baroreceptor dysfunction, since severe hypotension may result.

Aged↗

Functional significance of dendritic swelling after loud sounds in the guinea pig cochlea.

Exposure of the guinea pig cochlea to loud pure tones caused a dramatic swelling of afferent dendrites beneath the inner hair cell (IHC). This swelling occurred in a restricted region of the cochlea basalward of the exposure frequency location. For a 110 dB tone swelling was just detectable in 1 micron sections for a 18 3/4 min exposure and was clearly visible after a 22 1/2 min exposure. Swelling was reversible. Exposures which caused swelling produced a loss in sensitivity of the flat low frequency 'tail' of the frequency-threshold curves of single auditory neurons whose most sensitive frequency was a 1/2 octave higher than the exposure frequency. The findings are consistent with the notion that dendritic swelling causes a non-selective decrease in sensitivity to all frequencies of sound.

Animals↗

Noise-induced cochlear damage assessed using electrophysiological and morphological criteria: an examination of the equal energy principle.

Cochlear damage immediately following exposure to continuous pure tones of varying intensity and duration was assessed in anaesthetized guinea pigs. Indices of damage used were elevation of N1 thresholds and severity of swelling of the afferent dendrites beneath the inner hair cell. The results were not wholly consistent with the assumptions of the equal energy principle. Longer duration exposures resulted in greater N1 threshold elevation and more severe swelling of dendrites than short exposures of the same total energy.

Animals↗