Automated detection of microcalcification clusters for digital breast tomosynthesis using projection data only: a preliminary study.

Digital breast tomosynthesis (DBT) is a promising modality for breast imaging in which an anisotropic volume image of the breast is obtained. We present an algorithm for computerized detection of microcalcification clusters (MCCs) for DBT. This algorithm operates on the projection views only. Therefore it does not depend on reconstruction, and is computationally efficient. The algorithm was developed using a database of 30 image sets with microcalcifications, and a control group of 30 image sets without visible findings. The patient data were acquired on the first DBT prototype at Massachusetts General Hospital. Algorithm sensitivity was estimated to be 0.86 at 1.3 false positive clusters, which is below that of current MCC detection algorithms for full-field digital mammography. Because of the small number of patient cases, algorithm parameters were not optimized and one linear classifier was used. An actual limitation of our approach may be that the signal-to-noise ratio in the projection images is too low for microcalcification detection. Furthermore, the database consisted of predominantly small MCC. This may be related to the image quality obtained with this first prototype.

Distribution and function of muscarinic receptor subtypes in the ovine submandibular gland.

The effects of muscarinic receptor antagonists on responses to electrical stimulation of the chorda-lingual nerve were determined in pentobarbitone-anesthetized sheep and correlated to the morphology of tissue specimens. Stimulation at 2 Hz continuously, or in bursts of 1 s at 20 Hz every 10 s, for 10 min induced similar submandibular fluid responses (19 +/- 3 vs. 21 +/- 3 microl x min(-1) x g gland(-1)), whereas vasodilatation was greater during stimulation in bursts (-52 +/- 4 vs. -43 +/- 5%; P < 0.01). Continuous stimulation at 8 Hz induced substantially greater responses (66 +/- 9 microl x min(-1) x g gland(-1) and -77 +/- 3%). While atropine (0.5 mg/kg iv) abolished the secretory response at 2 and 20 Hz (1:10 s), a small response persisted at 8 Hz (<5%). The "M1-selective" antagonist pirenzepine (40 microg/kg iv) reduced the fluid response at all frequencies tested (P < 0.05-0.01), most conspicuously at 2 Hz (reduced by 69%). Methoctramine ("M2/M4-selective"; 100 microg/kg iv; n = 5) had no effect on fluid or the vascular responses but increased the protein output at 2 (+90%, P < 0.05) and 8 Hz (+45%, P < 0.05). The immunoblotting showed distinct bands for muscarinic M1, M3, M4, and M5 receptors, and immunohistochemistry showed muscarinic M1 and M3 receptors to occur in the parenchyma. Thus muscarinic M1 receptors contribute to the secretory response to parasympathetic stimulation but have little effect on the vasodilatation in the ovine submandibular gland. Increased transmitter release caused by blockade of neuronal inhibitory receptors of the M4 subtype would explain the increase in protein output.

A GATA-6 gene heart-region-specific enhancer provides a novel means to mark and probe a discrete component of the mouse cardiac conduction system.

The transcriptional programs that specify the distinct components of the cardiac conduction system are poorly understood, in part due to a paucity of definitive molecular markers. In the present study we show that a cGATA-6 gene enhancer can be used to selectively express transgenes in the atrioventricular (AV) conduction system as it becomes manifest in the developing multichambered mouse heart. Furthermore, our analysis of staged cGATA-6/lacZ embryos revealed that the activity of this heart-region-specific enhancer can be traced back essentially to the outset of the cardiogenic program. We provide evidence that this enhancer reads medial/lateral and anterior/posterior positional information before the heart tube forms and we show that the activity of this enhancer becomes restricted at the heart looping stage to AV myocardial cells that induce endocardial cushion formation. We infer that a deeply-rooted heart-region-specific transcriptional program serves to coordinate AV valve placement and AV conduction system formation. Lastly, we show that cGATA-6/Cre mice can be used to delete floxed genes in the respective subsets of specialized heart cells.

Presence and effects of pituitary adenylate cyclase activating peptide in the submandibular gland of the ferret.

Pituitary adenylate cyclase activating peptide (PACAP), a recently described vasoactive intestinal peptide-like neuropeptide, was found to be present in neurons in the submandibular gland of the ferret, where PACAP-immunoreactive nerve fibers were distributed around blood vessels, acini and ducts. Most of the PACAP-immunoreactive fibres were distinct from those storing vasoactive intestinal peptide. PACAP occurs in tissues as PACAP1-38 and PACAP1-27. PACAP1-38 and PACAP1-27 but not PACAP16-38 displayed biological activity with about the same potency. They exerted vasodilator effects on the submandibular vasculature, which resulted in a greater fall in vascular resistance than an equimolar dose of vasoactive intestinal peptide. The vasodilator response was independent of muscarinic receptor activation. Neither vasoactive intestinal peptide nor PACAP alone evoked any flow of saliva. However, both vasoactive intestinal peptide and PACAP enhanced the fluid response to acetylcholine, and the flow of saliva as well as the output of protein in response to parasympathetic nerve stimulation, vasoactive intestinal peptide being more potent than PACAP. In vitro, protein was released from submandibular gland tissue in response to both vasoactive intestinal peptide and PACAP, vasoactive intestinal peptide being more potent than PACAP. PACAP (and vasoactive intestinal peptide) exerted its in vitro effect following adrenoceptor and muscarinic blockade and following degeneration of sympathetic nerves. Sympathetic denervation combined with parasympathetic preganglionic denervation resulted in supersensitivity to both vasoactive intestinal peptide and PACAP. The fact that PACAP and vasoactive intestinal peptide occur in different nerve fibre populations suggests different roles for the two peptides in the submandibular gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced adrenal cortical sensitivity to ACTH in lambs with cut splanchnic nerves.

The possibility that the sensitivity of the adrenal cortex to endogenous ACTH may be affected by splanchnic nerve activity has been investigated in conscious, weaned, 5- to 8-month-old lambs. The animals were atropinized (0.5 mg/kg) and tested with an i.v. infusion of noradrenaline (333 ng/kg per min for 10 min), which produced a significant rise in the mean concentration of both ACTH and cortisol in the arterial plasma. In lambs tested at least 7 days after section of both splanchnic nerves, just below the diaphragm, the rise in plasma ACTH concentration was significantly greater, and that in plasma cortisol significantly less, than in control lambs. The mean plasma ACTH and cortisol concentrations were linearly related to one another in both groups (r = 0.93 and 0.92) but the sensitivity of the adrenal cortex to the steroidogenic action of ACTH appeared to have been roughly halved 1 week after bilateral splanchnic nerve section.

Submandibular secretory and vascular responses to stimulation of the parasympathetic innervation in anesthetized cats.

Submandibular secretory responses to stimulation of the parasympathetic chorda-lingual nerve in anaesthetized cats have been investigated before, during, and after intracarotid infusion of endothelin-1 (ET-1), which reduced blood flow through the gland by 64+/-7%. Stimulation at different frequencies (2, 4, 8, and 16 Hz) evoked a frequency-dependent increase in the flow of submandibular saliva, sodium concentration and output, and output of both potassium and protein. The reduction in submandibular blood flow, which occurred in response to the infusion of ET-1, was associated with a decreased flow of saliva and a diminished output of both sodium and protein. The flow of saliva was linearly related to submandibular blood flow both in the presence and absence of ET-1. It is concluded that submandibular secretory responses to electrical stimulation of the parasympathetic innervation can be significantly attenuated by reducing the blood flow through the gland by ET-1 infusion, just as it is when the blood flow is reduced by hypotension.

Effects of prolonged reduction in blood flow on submandibular secretory function in anesthetized sheep.

Submandibular vascular and secretory responses to parasympathetic chorda-lingual (C-L) stimulation were investigated in anesthetized sheep before, during, and after an intracarotid (ic) infusion of endothelin-1 (ET-1). Stimulation of the peripheral end of the C-L nerve at 4 and 8 Hz produced a frequency-dependent reduction in submandibular vascular resistance (SVR) associated with a frequency-dependent increase in submandibular blood flow, salivary flow, and Na+, K+, and protein output from the gland. During stimulation at 4 Hz, ic ET-1 significantly increased SVR (P < 0.01), without significantly affecting either the aortic blood pressure or heart rate. Submandibular blood flow (SBF) was reduced by 48 +/- 4% and the flow of saliva by 50 +/- 1%. The effect on blood and salivary flow persisted for at least 30 min after the infusion of ET-1. The reduction in SBF was associated with a diminution in the output of Na+,K+, and protein in the saliva (P < 0.01). These effects persisted for 30 min after the infusion of ET-1 had been discontinued and were linearly related to the flow of plasma throughout.

Submandibular responses to stimulation of the parasympathetic innervation in anesthetized sheep.

Submandibular secretory and vascular responses to stimulation of the parasympathetic innervation and the output of vasoactive intestinal peptide (VIP) were investigated in anaesthetized sheep in the presence and absence of atropine (>/=0.5 mg/kg). In the absence of atropine, parasympathetic stimulation caused an increase in the flow of saliva and a decrease in submandibular vascular resistance; the latter response persisted after the administration of atropine and was then significantly reduced at the lowest but not at the higher frequencies tested. The output of VIP from the gland was frequency dependent over the range of 10-20 Hz (continuously) and significantly increased after atropine (P < 0.02). Furthermore, the fall in vascular resistance was linearly related to log VIP output after total muscarinic blockade. Intracarotid infusions of synthetic VIP produced dose-dependent falls in submandibular vascular resistance, together with a corresponding increase in submandibular blood flow. It is concluded that the atropine-resistant vasodilatation that occurs in this gland during parasympathetic stimulation is likely to be due largely, if not entirely, to the release of VIP.

Neuropeptide Y (NPY) reduces myocardial perfusion and inhibits the force of contraction of the isolated perfused rabbit heart.

Isolated rabbit hearts, perfused under constant pressure (Langendorff technique) were used to study the effect of neuropeptide Y (NPY) on heart rate, force of heart contraction and rate of myocardial perfusion. No significant net change in heart rate was noted. A dose-dependent negative inotropic effect was consistently demonstrated which was characterised by slow onset and was often preceded by a transient positive inotropic response. Addition of small doses of NPY resulted in a prompt reduction in flow of the perfusate through the coronary vasculature. Since NPY is present locally in cardiac nerves, these effects may have physiological importance.

The effect of parasympathetic postganglionic denervation on parotid salivary protein secretion in anaesthetized sheep.

Effects of unilateral parasympathetic denervation of ovine parotid glands were examined in anaesthetized sheep 21-28 days after nerve section. Parasympathetic denervation reduced the mass of the ipsilateral gland while increasing that of the contralateral gland to the extent that total gland mass was greater than in sheep with normally innervated glands. The spontaneous secretion (8.8 +/- 1.1 microl min(-1) g gland(-1)) was significantly less from denervated than from innervated glands of normal control animals (26.0 +/- 2.7 microl min(-1) g gland(-1); P< 0.01) and contained more protein. Rates of flow, and the outputs of sodium and potassium, in response to sympathetic stimulation, were similar from normally innervated and chronically denervated glands, when allowance was made for the discrepancy in weights, whereas the output of protein was significantly enhanced following parasympathetic denervation (innervated--31.4 +/- 7.3 microg g gland(-1), denervated--83.4 +/- 26.6 microg g gland(-1); P< 0.05). Intra-arterial infusions of acetylcholine (130 pmol min(-1) kg(-1)) elicited a flow of parotid saliva, the protein content of which was significantly enhanced by prior parasympathetic denervation. Intra-arterial infusions of vasoactive intestinal peptide (VIP; 2.5 pmol min(-1) kg(-1)) produced a small but statistically significant (P< 0.05) increase in the flow of parotid saliva from the contralateral, innervated but not from denervated glands. It also caused a small increase in protein output, which was significantly enhanced by prior denervation. VIP had no synergistic effect on the parotid responses to acetylcholine. The results show that the parasympathetic innervation to the parotid gland of the sheep exerts important trophic effects on the gland. Interaction of adrenergic and cholinergic receptors makes an important contribution to stimulation of the secretion of protein and prior denervation potentiates the protein responses to both acetylcholine and VIP.

Autonomic control of protein production by the parotid gland of the sheep.

The role of adrenoceptors in the control of parotid salivary function has been investigated in anaesthetized sheep. The enhancement of parotid protein output that occurs when the parasympathetic and sympathetic innervations to the gland are stimulated simultaneously in bursts at a low frequency (20 Hz for 1 s at 10-s intervals) was effectively abolished by pretreatment with propranolol (> or = 1.0 mg kg(-1), i.v., P < 0.001), without a comparable reduction in the flow of saliva or in the output of sodium or potassium. Secretion of protein was similarly augmented by simultaneous stimulation of the sympathetic innervation and an intracarotid infusion of acetylcholine (0.4-0.6 microg min(-1) g gland(-1)). This effect was also abolished by pretreatment with propranolol. Pretreatment with phentolamine (>1.0 mg kg(-1), i.v.) had no effect on the output of protein that occurred during combined stimulation of the parasympathetic and sympathetic innervations but increased the flow of saliva and the output of electrolytes. Stimulation of the parasympathetic innervation to the parotid gland caused a substantial fall in vascular resistance, which was reduced by the administration of atropine (0.5 mg kg(-1)). Stimulation of the sympathetic innervation caused a substantial rise in parotid vascular resistance in atropinized sheep. This effect was greater during continuous stimulation than during intermittent stimulation and enhanced by pretreatment with propranolol. It was virtually eliminated by pretreatment with phentolamine. It is concluded that the enhancement of protein output from the ovine parotid gland, that occurs during combined stimulation of the parasympathetic and sympathetic innervations at relatively low frequencies, depends upon interaction between cholinergic muscarinic and beta-adrenergic receptors. The vasoconstriction that occurs during sympathetic stimulation alone can be accounted for by activation of alpha-adrenoceptors.

Pancreatic exocrine responses to parasympathetic stimulation in anaesthetized pigs.

Pancreatic exocrine responses to stimulation of the peripheral ends of the vagus nerves intermittently have been investigated in anaesthetized pigs and compared with the effects of continuous stimulation at corresponding frequencies. At relatively low frequencies < or =20 Hz in bursts or 2 Hz continuously) both the flow of pancreatic juice and the output of protein therein were potentiated by stimulating in bursts. Thus stimulation at 20 Hz in bursts produced a significantly greater flow of pancreatic juice than stimulation at 2 Hz continuously (10.9+/-0.9 compared to 4.8+/-0.7 microl min(-1) (g gland)-1 , respectively; P<0.01). Likewise the output of protein during intermittent stimulation at 20 Hz (144+/-23 microg min(-1) (g gland)-1) far exceeded that produced during continuous stimulation at 2 Hz (49+/-9 microg min(-1) (g gland)-1; P<0.01). Both differences were abolished by atropine (0.5 mg kg(-1) i.v.), which augmented the flow during continuous stimulation (to 8.7 +/- 1.5 microl min(-1) (g gland)-1; P<0.05 at 2 Hz) and substantially reduced the output of protein during intermittent stimulation (to 27+/-7 ng min(-1) (g gland)-1; P<0.01 at 20 Hz in bursts). These results show that a variety of pancreatic exocrine responses can be enhanced by stimulating the parasympathetic innervation in bursts. They are also consistent with the contention that the secretion of protein from the gland, in response to parasympathetic stimulation, is dependent mainly on activation of muscarinic receptors. They confirm that the flow of pancreatic juice is due mainly to the release of VIP and show that, in the absence of atropine, this is restricted by muscarinic inhibition which may be presynaptic as elsewhere.

Effects of endothelin on submandibular salivary responses to parasympathetic stimulation in anaesthetized sheep.

Submandibular responses to stimulation of the parasympathetic chorda tympani nerve have been investigated in anaesthetized sheep before, during and after an intracarotid infusion of endothelin, which reduced the blood flow through the gland by 56+/-5%. Stimulation of the peripheral end of the chorda tympani nerve produced a frequency-dependent increase in the flow of submandibular saliva, and in sodium, potassium and protein output. The reduction in submandibular blood flow, which occurred in response to endothelin, was associated with a decrease in the flow of saliva at all frequencies tested amounting on average to 44+/-6% (P<0.01). The flow of saliva was linearly related to the blood flow before and after endothelin. Both parameters were also linearly related during the infusion of endothelin and the regression lines were parallel. Salivary sodium concentration was significantly increased at the lower frequencies (1 and 2 Hz). Protein output was generally reduced but the difference only achieved statistical significance during stimulation at 1 Hz (P<0.01). Thus, submandibular secretory responses to parasympathetic stimulation are significantly attenuated by reducing the blood flow through the gland in this way.

Recent physiological studies of the alimentary autonomic innervation.

The optimum pattern of stimulation of the VIP-ergic fibres in the submaxillary gland of the cat has been investigated by comparing the effects of continuous stimulation at 2 Hz for 10 min with those of stimulation at 20 Hz for 1 sec intervals for the same period. Both the fall in submaxillary vascular resistance (SVR) and release of VIP from the gland are significantly increased when the same total number of impulses is delivered in bursts at the higher frequency. Comparison of submaxillary responses to stimulation in 1 sec bursts, over a wide range of frequencies, has shown that, in atropinised cats, the fall in SVR is linearly related to stimulus frequency over the range 2-60 Hz, and maximal at 80 Hz. In addition, the fall in SVR is linearly related to stimulus frequency over the range 2-60 Hz, and maximal at 80 Hz. In addition, the fall in SVR is linearly related to log VIP output from the gland over the whole of the frequency range 2-160 Hz. Stimulation in 1 sec bursts at 10 sec intervals has also shown that certain non-peptidergic autonomic responses are optimal at much higher stimulus frequencies than has hitherto been supposed on the basis of classical studies employing continuous stimulation. It is concluded that it is no longer justified to assume that autonomic nerve fibres are invariably characterised by low natural discharge frequencies or that they necessarily fire at relatively constant rates. The results obtained using bursts of stimuli also show how differential responses can be obtained in the same tissue simply by varying the stimulus frequency and pattern.

Aspects of autonomic and neuroendocrine function.

This article provides a brief review of aspects of autonomic and neuroendocrine function studied initially in collaboration with the late Marian Silver. The importance of the sympathetic innervation to the liver in the control of glycogenolysis was established in anaesthetised animals of various species. Otherwise the work has been carried out mainly in conscious animals under strictly physiological conditions and below behavioural threshold. Investigations of the role of the autonomic innervation to the endocrine pancreas in controlling the release of pancreatic hormones, led to the realisation that the parasympathetic innervation mediates responses to glycaemic stimuli while the sympathetic innervation mediates responses to any form of stress. Studies of adrenal medullary function have confirmed that its threshold for many forms of stress is much higher than that of other components of the sympathetic system and revealed the importance of the pattern of electrical stimulation in determining the rates of release of catecholamines, enkephalins, corticotrophin-releasing factor (CRF) and adrendocorticotrophin (ACTH). The splanchnic sympathetic innervation to the adrenal cortex also plays an important role in determining glucocorticoid output by sensitising the cells to ACTH, probably mainly by the release of vasoactive intestinal peptide (VIP) from cortical nerve terminals. Finally studies of feeding in milk-fed calves have shown that suckling is associated with a remarkable hypertension and tachycardia. These cardiovascular effects are due to a selective sympathetic discharge, which does not involve the adrenal medullae, or the release of neuropeptide Y (NPY) and, at least in the calf, can be attributed to activation of adrenoceptors.

Adrenal medullary responses to splanchnic nerve stimulation in new-born calves.

Right adrenal medullary and various cardiovascular responses to stimulation of the peripheral end of the right splanchnic nerve have been investigated in conscious calves 24-48 h after birth and compared with those obtained previously in older conscious calves. The results show that splanchnic nerve stimulation produces a smaller rise in mean aortic blood pressure and haematocrit in new-born calves than occurs in older animals. The fall in adrenal vascular resistance is also reduced, as is the amount of catecholamine released from the adrenal medulla, at 24-48 h. Although the absolute amounts of adrenaline and noradrenaline released in response to splanchnic nerve stimulation were significantly less in 24-48 h old calves, the ratio (3:2) was the same as that found in 2-5 week old animals and that in which the two amines are stored in the gland. The results confirm the contention that the sympathetic innervation is relatively immature immediately after birth in this species and that functional maturation occurs gradually over a period of weeks. However, they also show that the ratio in which adrenaline and noradrenaline are released from the adrenal medullae provide no index of this process, as had previously been suggested.

Adrenal catecholamine output in response to stimulation of the splanchnic nerve in bursts in the conscious calf.

1. Different patterns of stimulation have been applied to the peripheral end of the right splanchnic nerve, below behavioural threshold, in conscious 2-5 week-old calves. 2. The effects of continuous stimulation at 4 Hz for 10 min were compared with those of stimulation at 40 Hz in 1 s bursts at 10 s intervals for the same period. Delivering the same total number of impulses in the form of bursts in this way increased the output of both adrenaline and noradrenaline and this increase was statistically significant in the case of adrenaline (P less than 0.02) but not noradrenaline. 3. The effects of stimulation in 1 s bursts at 10 s intervals for 2-3 min were investigated over the frequency range 10-150 Hz and compared with the effects of continuous stimulation over the range 1-15 Hz obtained previously in conscious calves of the same age (Edwards, Furness and Halle, 1980). The output of adrenaline but not noradrenaline was found to significantly greater in response to stimulation in bursts at frequencies of up to 40 Hz than when the equivalent number of impulses were delivered at a constant rate (P less than 0.02). 4. It is concluded that the release of catecholamines from the adrenal gland is maximal at relatively high frequencies (40-100 Hz) when the impulses are delivered in bursts.

The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves, sheep, dogs, cats and pigs.

1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in calves, sheep, dogs, cats and pigs after removal of both adrenal glands.2. Stimulation of both splanchnic nerves produced comparable hyperglycaemic and glycogenolytic effects in sheep, dogs and cats; the mean liver glycogen concentration was reduced by between 7.0 and 10.5 mg/g, five min after stimulation was discontinued, at which time the mean plasma glucose concentration had risen by between 126 and 137 mg/100 ml.3. In five 3-5 week-old calves which were tested under identical conditions the mean liver glycogen concentration was reduced by 13.3 +/- 1.9 mg/g and the plasma glucose concentration raised by 216 +/- 1.9 mg/100 ml., 5 min after stimulation was terminated.4. In pigs, stimulation of both splanchnic nerves invariably produced a rise in the plasma glucose concentration, even when the concentration of glycogen in the liver was less than 5 mg/g before stimulation. The response was, nevertheless, considerably smaller in these animals than in any of the other species investigated.5. Splanchnic nerve stimulation also caused a rise in mean aortic blood pressure and blood haematocrit during the period of stimulation; changes of approximately the same order of magnitude were encountered in all five species.6. Dogs were found to resemble calves in that the hyperglycaemic response to stimulation of a single splanchnic nerve did not differ significantly from that obtained when both were stimulated simultaneously; furthermore, either nerve was found to be equally effective.7. In cats the change in plasma glucose concentration in response to stimulation of a single splanchnic nerve was always less than that which occurred in response to bilateral stimulation although comparable changes in blood haematocrit occurred in both groups of animals.8. It is concluded that stimulation of the splanchnic nerves causes break-down of glycogen in the livers of various unrelated species of adult animals but that the magnitude of the hyperglycaemic response in the young calf provides further evidence of the importance of the sympathetic system in the control of metabolism in the young animal.

The sensitivity of the hepatic glycogenolytic mechanism ot stimulation of the splanchnic nerves.

1. The sensitivity of the hepatic glycogenolytic mechanism to splanchnic nerve stimulation at relatively low frequencies has been investigated in adrenalectomized calves, dogs and cats.2. In young calves the hyperglycaemic response to splanchnic nerve stimulation at 1.0 c/s for 5 min increased steadily during the first 2 weeks after birth.3. The hyperglycaemic response to splanchnic nerve stimulation for 5 min was directly related to frequency of stimulation within the range 0.5-4.0 c/s in calves tested 2-5 weeks after birth. Pronounced rises in plasma glucose concentration also occurred in calves of this age in response to maximal stimulation (20 c/s) for shorter periods (30 sec) whereas occlusion of the portal vein for the same period produced no comparable effect.4. The effects of splanchnic nerve stimulation for prolonged periods were also investigated in 2- to 5-week-old calves. Under these conditions increased concentrations of glucose in the plasma were maintained for periods of up to 90 min and fell towards the initial values when stimulation was discontinued.5. Prolonged stimulation of the peripheral ends of both splanchnic nerves at either 2.0 or 4.0 c/s produced a transient reversal of hypoglycaemia in calves pretreated with large doses of insulin; both the extent and duration of these responses were related to frequency of stimulation.6. The hyperglycaemic response to bilateral splanchnic nerve stimulation was directly related to frequency of stimulation within the range 0.5-4.0 c/s in adrenalectomized dogs. Comparable responses were obtained in adrenalectomized cats in response to stimulation at 2.0 c/s, but stimulation at 1.0 c/s produced no rise in mean plasma glucose concentration in these animals.7. The sensitivity of the hepatic glycogenolytic mechanism has been assessed in relation to the associated changes in haematocrit and mean aortic blood pressure under the same conditions.8. The results of these experiments support the contention that tonic changes in sympathetic efferent activity are associated with variations in the rate at which glucose is released from the liver under physiological conditions.