Influence of selection for breast muscle mass on myosin isoform composition and metabolism of deep pectoralis muscles of male and female turkeys.

Advances in genetic selection and nutrition have resulted in rapid growth rates and increased muscle mass, predisposing turkeys to muscle disorders such as deep pectoral myopathies and increasing the incidence of pale, soft, and exudative muscle. The objective of this study was to determine if selection for breast muscle mass created an increase in anaerobic capacity of the deep pectoralis muscle. A total of 67, 18-wk-old, male and female turkeys from two male (tom) lines and one female (hen) line were used. Each bird was anesthetized and one deep pectoralis muscle was electrically stimulated via the pectoral nerve. Muscle pH was recorded every 30 s for 4 min of stimulation and every 1 min for a 10-min recovery period. Non-stimulated muscles, contralateral to the stimulated side, were assayed for lactate dehydrogenase (LDH) and glyceraldehyde phosphate dehydrogenase (GAPDH). Myosin isoforms were resolved with SDS-PAGE. Line or gender had no effect on rate of pH decline during or after stimulation. Declines in pH during stimulation were greater than during the recovery period (0.06 vs. 0.02 U/min). The lightweight male line (LM) had the greatest breast muscle mass as a percentage of body weight (P < 0.05) and the greatest LDH [293 mmol nicotinamide adenine dinucleotide (NADH) min(-1)microg(-1); P < 0.0001] and GAPDH (0.4452 mmol NADH min(-1)microg(-1); P < 0.05) activities. Hens had greater percentages breast weight than males (P < 0.05) and a tendency for increased enzyme activities. The LM line had the largest ratio (2.33:1) (P < 0.05) of adult-to-neonatal myosin. Genetic selection for breast muscle mass resulted in an increased ratio of adult-to-neonatal myosin and increased anaerobic capacity. This effect on myosin isoform composition and anaerobic capacity supports handling modifications that are line specific to minimize meat quality defects.

Sphingomyelin metabolism in rat liver after chronic dietary replacement of choline by N-aminodeanol.

Sphingomyelin (SM) is a structural element of cell membranes and lipoproteins, and participates in signal transduction. To determine whether a choline analog (N-amino-N,N-dimethylaminoethanol, N-aminodeanol, NADe) can be substituted for choline in the SM of liver, rats (male, Sprague-Dawley-derived) were fed a diet that was low in choline and methionine, and contained 35.5 mmol of NADe/kg. After 18 months, liver plasma membranes and microsomes contained 48.9 +/- 3.6 and 93.6 +/- 6.9 nmol/mg protein of phosphatidyl-NADe, respectively, and 3.2 +/- 0.2 and 3.5 +/- 0.1 nmol/mg protein of ceramide phospho-NADe. The SM content of microsomes from NADe-fed rats was about one-third lower than for the control, and phosphatidylcholine (PC) was reduced by < 10%; there was also a small decrease in PC, but not SM, in plasma membranes. In vitro assays of enzymes involved in SM metabolism found no change in PC:ceramide cholinephosphotransferase, but the NADe-fed animals had higher phosphatidylethanolamine:ceramide ethanolaminephosphotransferase activity, greater incorporation of methyl groups from [methyl-3H]-S-adenosyl methionine into SM, and a lower neutral sphingomyelinase activity. These results show that NADe-fed rats from considerable amounts of ceramide phospho- and phosphatidyl-NADe; however, liver plasma membranes retain relatively normal levels of PC and SM, perhaps due to increases in the de novo pathway for SM synthesis and decreases in SM turnover.

Longer term quality of life and outcome in stroke patients: is the Barthel index alone an adequate measure of outcome?

OBJECTIVES: To consider whether the Barthel Index alone provides sufficient information about the long term outcome of stroke. DESIGN: Cross sectional follow up study with a structured interview questionnaire and measures of impairment, disability, handicap, and general health. The scales used were the hospital anxiety and depression scale, mini mental state examination, Barthel index, modified Rankin scale, London handicap scale, Frenchay activities index, SF36, Nottingham health profile, life satisfaction index, and the caregiver strain index. SETTING: South east London. SUBJECTS: People, and their identified carers, resident in south east London in 1989-90 when they had their first in a life-time stroke aged under 75 years. INTERVENTIONS: Observational study. MAIN OUTCOME MEASURES: Comparison and correlation of the individual Barthel index scores with the scores on other outcome measures. RESULTS: One hundred and twenty three (42%) people were known to be alive, of whom 106 (86%) were interviewed. The median age was 71 years (range 34-79). The mean interval between the stroke and follow up was 4.9 years. The rank correlation coefficients between the Barthel and the different dimensions of the SF36 ranged from r = 0.217 (with the role emotional dimension) to r = 0.810 (with the physical functioning dimension); with the Nottingham health profile the range was r = -0.189 (with the sleep dimension, NS) to r = -0.840 (with the physical mobility dimension); with the hospital and anxiety scale depression component the coefficient was r = -0.563, with the life satisfaction index r = 0.361, with the London handicap scale r = 0.726 and with the Frenchay activities index r = 0.826. CONCLUSIONS: The place of the Barthel index as the standard outcome measure for populations of stroke patients is still justified for long term follow up, and may be a proxy for different outcome measures intended for the assessment of other domains.

A long-term follow-up of stroke patients.

BACKGROUND AND PURPOSE: Two hundred ninety-one residents of southeast London, younger than 75 years, suffered their first stroke in 1989/1990. The objectives of this study were to determine the long-term outcome of this cohort of stroke patients in terms of impairment, disability, handicap, and quality of life and their use of services and prevention measures subsequent to their stroke. METHODS: The survivors and their identified caregivers were traced and completed a structured interview questionnaire that included the Barthel Index, modified Rankin Scale, Hospital Anxiety and Depression Scale (HAD), Mini-Mental State Examination, Frenchay Activities Index, and Caregiver Strain Index. RESULTS: One hundred twenty-three people (42%) were alive, of whom 106 were interviewed. The mean interval between the stroke and the long-term follow-up was 4.9 years. Thirty-one of the survivors (29%) were severely or moderately disabled, 39 (37%) were mildly disabled, and 36 (34%) were functionally independent. Of the 96 people who completed the HAD, 35 (36%) had scores suggesting that they were depressed or had borderline depression. The most likely nontherapy services to have been provided were chiropody and district nursing. Five people had received respite care. Of the 104 subjects for whom information about their home was available, 53 (51%) had had an adaptation. Seventy-five people (71%) had an aid or appliance. Sixty-five people (61%) were on aspirin, and an additional 14 (13%) were on warfarin. Fifty subjects (47%) identified a main caregiver. No one with a moderate or more severe disability was living at home without an identified caregiver. CONCLUSIONS: The levels of both health and social service provision are likely to be inadequate for this population. The use of prevention measures is encouraging. There is a clear need for a coordinated policy to guide assessment and management across sectors.

Apneustic breathing provoked by limbic influences.

We describe a 64-year-old man with cerebrovascular disease who had an acute stroke characterised by pseudobulbar palsy, facial weakness, and pyramidal signs. He developed frequent emotional outbursts followed by periods of apneusis. Between these episodes he breathed with a regular and unvarying rate and tidal volume. Autopsy showed extensive cortical, subcortical and pontine infarction. The respiratory pattern indicated a dissociation between voluntary and automatic pathways. The descending limbic pathways were preserved but an abnormal pattern of automatic breathing (ie, apneusis) occurred because of the presence of bilateral pontine infarction.

Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity.

Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counterparts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain similarities to individuals with MCS. In addition to their greater sensitivity to DFP, the FSL rats are more sensitive to nicotine and the muscarinic agonists arecoline and oxotremorine, suggesting that the number of cholinergic receptors may be increased, a conclusion now supported by biochemical evidence. The FSL rats have also been found to exhibit enhanced responses to a variety of other drugs, including the serotonin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine antagonist raclopride, the benzodiazepine diazepam, and ethanol. MCS patients report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients. The FSL rats also exhibit reduced activity and appetite and increased REM sleep relative to their FRL controls. Because these behavioral features and the enhanced cholinergic responses are also observed in human depressives, the FSL rats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depression, both before and after onset of their chemical sensitivities, so cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the commonalities and differences between MCS patients, human depressives, and FSL rats will help to elucidate the mechanisms underlying MCS and could lead to diagnostic approaches and treatments beneficial to MCS patients.

Continuing the search for cholinergic factors in cognitive dysfunction.

The objective of the experiments reported here was to explore three hypotheses regarding cholinergic processes underlying the development of progressive degenerative dementia (PDD). One possibility involved the downregulation of muscarinic receptors (mAChR) with aging, thus reducing the capability of the cholinergic system to support normal memory and other cognitive functions. The results of downregulation to 10% of normal produced only a temporary effect, the system having the capability to repair the damage. A second hypothesis predicted that a chronic hypocholinergic state can produce structural changes that are reflected in persisting cognitive dysfunctions. Chronic administration of a false cholinergic transmitter in the diets of weanling rats mimicked such a state which, if maintained for a protracted period, produced many of the features of PDD in humans. When the diet was returned to normal, biochemical and physiological processes recovered fully. However, memory impairment continued. This suggested the possibility that the behavioral losses were mediated by persisting morphological changes in the CNS. The third hypothesis proposes that these changes may be due to cell loss resulting from impaired phospholipid metabolism. Changes in sphingomyelin, one of the two major Ch-containing lipids in cell membranes, could increase amounts of ceramide, an inducer of programmed cell death (apoptosis). Tests of this hypothesis are nearing completion.

Influence of moisture content of forage diets on intake and digestion by sheep.

To determine the effect of forage moisture content on intake and digestion kinetics in sheep, a metabolism trial was conducted using 16 mature wethers (44 kg BW) in a completely randomized design. Forage was harvested at two maturities in early spring from a naturalized pasture composed of temperate grass and legume species. Herbage was harvested at either 8 (early) or 16 cm (late) in height and fed after freezing (high-moisture) or as a dried hay. Intakes of DM (grams/[kilogram BW.75.day]), NDF, ADF, and CP (grams/day) (P < .05) and coefficients for DM, NDF, and ADF digestibilities were greater (P < .01) for hay than for high-moisture forage. Mean particulate retention times (MRT) were shorter (P < .05) for high-moisture forage (23.3 h) than for hay (30.7 h) diets. Early-harvested forages had shorter (P < .05) MRT values (23.9 h) than late-cut forages (30.1 h). Fractional passage rates of 1-mm nylon particles of specific gravity (SG) .90, 1.14, and 1.32 through the alimentary tract were influenced by moisture content of the forage (P < .10) and were faster for frozen forages and increased (P < .01) with an increase in SG. Nitrogen retention was greater (P < .01) for the hay than for the high-moisture forage. In situ DM digestion rates, determined using four ruminally fistulated wethers, showed no differences (P = .67) among forages. The results of this study indicate that differences in digestibilities between hays and high-moisture forages are most likely due to differences in digesta passage rates.

Accelerating behavioral recovery after cortical lesions. I. Homotopic implants plus NGF.

We recently demonstrated that fetal brain implants produced a significant recovery in the ability of insular cortex (IC)-lesioned rats to learn a conditioned taste aversion (CTA). We now report effects on the recovery of CTA and of a second measure of learning, inhibitory avoidance (IA), of supplementing the implants with nerve growth factor (NGF). Four groups of male Sprague-Dawley animals showing disrupted taste aversion following IC lesions, plus two control groups, received different experimental treatments: Group 1, unlesioned control; Group 2, homotopic IC implants without NGF; Groups 3 and 4, IC implants + NGF; Group 5, heterotopic occipital cortical implants + NGF; and Group 6, without an implant as a lesioned control. All groups except Group 4 were trained pre- and postimplant in the CTA paradigm. Two days after CTA testing postimplant, all groups received IA training. Behavioral results showed that insular cortex implants with NGF promoted recovery to control levels of the ability to learn both tasks at 15 days postimplant. Those animals that received occipital implants with NGF or insular cortex with vehicle or remained without implants did not show any significant behavioral recovery at 15 days postimplant. These findings suggest that NGF associated with homotopic implants facilitates recovery of learning abilities in insular cortex-lesioned rats and suggest that similar treatments with NTFs may have analogous effects when lesions involve other brain areas.

Accelerating behavioral recovery after cortical lesions. II. In vivo evidence for cholinergic involvement.

We recently demonstrated that insular cortex (IC) fetal implants supplemented by nerve growth factor (NGF) can accelerate the recovery of behavioral deficits induced by IC brain lesions. In the present report we describe results on in vivo assays of acetylcholine (ACh) turnover in the IC of rats subjected to the same brain lesion and implant treatments used in that research and for which detailed behavioral data are available. The neurochemical assays were carried out immediately after completion of the behavioral measurements. The assays showed that implants or NGF with heterotopic tissue continued to be associated with elevated levels of ACh and with deficits in learning and memory at a time postlesion when both behavior and ACh turnover in vivo, after treatment with homotopic implants and NGF combined, were at nonlesioned control levels. The results support the concept that, in vivo, the cholinergic neurotransmitter system is intimately involved in recovery from IC lesion-induced deficits in behavior and show that a combination of homotopic implant and NGF may be used as a means of manipulating that system to accelerate the repair of such deficits. Mechanisms by which this combination produces its effects are considered and the possibility is suggested that other neurotrophic factors (NTF) may also be useful when other types of brain lesions are involved.

Influence of forage species and diet particle size on the passage of digesta and nylon particles from the reticulorumen of steers.

To assess factors that influence the passage of digesta from the reticulorumen, ruminally fistulated steers (387 kg) were fed to appetite in a 4 x 4 Latin square design either orchardgrass (OG) (Dactylis glomerata L.) or switchgrass (SG) (Panicum virgatum L.) hays. The two hays were fed in either the long form or ground to pass a 2-cm screen. Steers fed OG diets had greater DMI (P < .05) than steers fed SG diets (11.7 vs 10.4 kg/d respectively). Particle size of ruminal digesta and feces determined by wet sieving was greater (P < .05) for the OG and long hay diets than for the SG and ground diets. Particle size of digesta collected from the anterior dorsal sac and anterior ventral sac of the rumen and from the reticulum did not vary (P > .25) with site. Conversely, ruminal concentrations of 1-mm nylon particles tended (P = .11) to be greater in the lower strata of the reticulorumen at 12 and 24 h after dosing. Neither a site effect nor a site x time-after-dosing interaction (P > .75) was observed for the 3- or 5-mm nylon particles, suggesting that a sorting process independent of specific gravity occurs in the rumen for smaller particles (before the reticulomasal orifice). Passage rate of the 1-mm nylon particles from the reticulorumen was greater (P < .01) for animals fed the SG than for those fed the OG diets, whereas for the 5-mm particles, passage rate was greater for the OG diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Pseudotumour cerebri associated with arteriovenous malformations.

The association of intracranial hypertension and arteriovenous malformations is described in two patients. Both patients had the typical clinical features of pseudotumour cerebri and were found to have intracranial arteriovenous malformations on arteriography. The mechanism of raised intracranial pressure in patients with arteriovenous malformations is discussed.

Improved rearrangement of the integrated Michaelis-Menten equation for calculating in vivo kinetics of transport and metabolism.

A multiple regression form of the integrated Michaelis-Menten equation was developed and evaluated with simulated data having controlled error. Both multiple and traditional linear regression fit errorless data perfectly, but multiple regression is much more stable with regard to accuracy and precision of estimating the Michaelis constant and maximum rate of reaction when data contain error. Bias in determining estimators of kinetic coefficients was -4 and -3% versus -56 and -35% with 10% error in the data. Multiple regression estimates for Michaelis constant and maximum rate of reaction directly as opposed to estimating 1/Km and maximum rate of reaction/Michaelis constant by linear regression. The difference in accuracy in estimating actual Michaelis constant, for example, is 4% versus 227% error with only 10% error in the data Precision of estimation is approximately the same as precision of the data for multiple regression. For the 800 data sets examined, R2 was always greater than .92 for multiple regression, but frequently was not significant for linear regression. The actual initial concentration was provided for linear regression but calculated by multiple regression with accuracy and precision equivalent to estimation of Michaelis constant and maximum rate of reaction. The multiple regression method has statistical power to determine treatment effects on Michaelis constant and maximum rate of reaction with a practical number of animals.

Selective breeding for increased cholinergic function: biometrical genetic analysis of muscarinic responses.

Biometric genetic analyses of behavioral and physiologic responses known to be related to muscarinic cholinergic receptors (hypothermia, hypoactivity, inhibited avoidance, and reduced responding for water) were studied in genetic crosses and backcrosses of the Flinders sensitive line (FSL) and Flinders resistant line (FRL) of rats. The FSL rats were more sensitive to the direct muscarinic agonists, arecoline and oxotremorine, and to the indirect agonist, physostigmine, than any other group. The next most sensitive group was the F1 x FSL backcross, followed by the F2, F1, F1 x FRL backcross, and the FRL, in that order. These differences between the genetic groups could be accounted for completely by either solely additive or additive plus dominance genetic factors. When dominance genetic factors contributed to the differences among groups (6 out of 15), the F1 responded like the FRL rats. The variance of the responses measured made it impossible to obtain reliable estimates of the number of genes involved in many instances; when such estimates were possible, several genes (greater than or equal to 3) appeared to be involved. We conclude that muscarinic sensitivity in rats is under genetic control, with the greatest contribution coming from additive genetic factors. Because the FSL rat appears to be a genetic animal model of depression, the finding of several genes influencing muscarinic responses may help account for the difficulties investigators have had in locating a single major gene or biological marker for human depressive disorders.

Characterization of a sustained-release estrogen implant on oviduct development and plasma Ca concentrations in broiler breeder chicks: modulation by feed restriction and thyroid state.

The effect of estradiol-17 beta (E2) given as a sustained-release implant (Compudose 200) on concentrations of plasma calcium (Ca) and the development of the chick shell gland has been investigated in food-restricted and thyroid hormone-treated 6- to 8-week-old broiler breeder pullets. Chicks implanted with 0, 0.5, 1.0, 1.5, 2.0, and 3.0 Compudose pellets for 24 days (n = 6/group) revealed a dose-response relationship between plasma E2 and Ca and on oviduct growth. Plasma E2 concentrations were characterized by an initial burst phase for approximately 17 days, followed by a constant release phase. Histologic examination of shell gland tissue confirmed the dose related E2-induced development of microvilliated epithelium and tubular glands over time. Feed restriction initiated at 2 weeks of age markedly increased the response to the E2 implants. Birds (n = 8/group) implanted with 2 pellets and feed restricted had increased plasma concentrations of E2 and Ca, and increased growth of the oviduct (P less than 0.01) as compared to ad libitum implanted birds. In a separate study birds (n = 6/group) had restricted access to feed from 8 weeks of age and were implanted with 0, 2, 4, or 8 pellets. At intervals from 9 to 45 days after implantation one bird from each group was killed. Although concentrations of plasma Ca were significantly greater in feed-restricted birds (P less than 0.01), oviduct growth was only marginally increased by the food restriction program. Plasma Ca concentrations in broiler breeder pullets (n = 8/group) implanted with 1 or 3 pellets and injected with T3/T4 (100 micrograms/day) were significantly decreased (P less than 0.05). Injection of thyroid hormone also marginally decreased shell gland epithelial cell height (P less than 0.05) and development of microvilli (P less than 0.05). There was no effect of the administration of the goitrogen, propylthiouracil (10 micrograms/day im), on the E2 induced development of the shell gland.

Incomplete reversibility of an experimentally induced hypocholinergic state: biochemical and physiological, but not behavioral, recovery.

In previous reports, we described the experimental development of a hypocholinergic state in rats following the total replacement of dietary choline by an artificial isostere, N-aminodeanol (NADe). NADe shares most of the physicochemical and biochemical characteristics of choline (Ch) but is utilized less efficiently in pathways leading to the formation of both acetylcholine and phospholipids. This experimental model mimics many of the features of human degenrative dementias. We now discuss the behavioral and physiological effects of restoring a normal diet after the hypocholinergic state has become well established. The procedure by which that state was induced has been described in detail in earlier publications. After replacing Ch in the diets of weanling rats for 270 days, NADe replaced 70-85% of the phospholipid-bound Ch in plasma, brain, and peripheral tissue. When dietary NADe was removed and Ch was restored in the diet, NADe disappeared and plasma and erythrocyte (RBC) choline levels returned to normal within 30-60 days. Quinuclidinyl benzilate (QNB) binding showed that muscarinic receptors continued to be depressed in animals remaining on the NADe diet, but returned to control levels in the reversal group. There were no differences in cholinesterase activity among the three treatments. Choline acetyltransferase activity returned to control levels, while continuing to be lower in the NADe animals. Liver lipids were elevated in the latter and not significantly different in the control and reversal groups. Among physiological functions, body weight increased more rapidly in the reversal group than in animals continuing on the NADe diet. Brain weights of the reversal animals were significantly greater than those of animals not reversed, but less than controls. Core body temperatures did not differ from controls at any time during the reversal period. Behaviorally, nociceptive thresholds indicative of sensory-reflexive and sensory-perceptual responses remained significantly below normal, that is, a hyperalgesic state. Reversal animals also remained hyperactive and displayed memory significantly poorer than those on the normal diet, that is, no improvement over animals continuing on NADe. In general, the results suggest that behavioral losses induced by NADe reflect persisting changes in the CNS, despite essentially complete recovery of biochemical parameters. The changes may be morphological or be associated with adaptive changes in other neurochemical events in the CNS.

Comparison of urea treatment with established methods of sorghum grain preservation and processing on site and extent of starch digestion by cattle.

To determine the effect of dry (D); reconstituted and ensiled (R); reconstituted and acid-treated (A); and urea-treated, high-moisture (U) sorghum grain on starch digestibility, four Angus x Hereford steers (means BW = 350 kg) with duodenal and ileal cannulas were used in a 4 x 4 Latin square design. Diets consisting of 69% ground sorghum grain were fed every 2 h in equal portions (8.2 kg/d). Diets averaged 46.5% starch and 12% CP, except for U, which averaged 14% CP due to urea treatment. Ytterbium attached to sorghum was used as a particulate marker. Duodenal, ileal, and fecal samples were taken 1 h postfeeding after a 14-d adaption to diets. Whole samples were analyzed. Preduodenal starch digestion (%) was 89, 83, 76, and 70, and starch digestion over the total tract was 99, 97, 95 and 91 for R, U, A, and D, respectively. Starch digestion proximal to each site (duodenum and ileum) was enhanced (P less than .05) by R and U compared with D. Within the small intestine, there was a linear relationship (P less than .003) between starch digestion and daily starch supply. However, digestibility of starch in the small intestine (mean = 45%) was not different among diets. Apparent digestibility of starch in the large intestine was not significantly different from digestibility in the small intestine. Urea-treated sorghum grain was equivalent to reconstituted, ensiled sorghum in digestion characteristics and was superior to dry sorghum.

An automated method for studying drug effects on problem solving by small laboratory animals.

The design and construction details of a method for studying problem solving by small animals is described. The form of motivation is escape from water in a T-shaped apparatus, thus eliminating possible confounding effects involved when food or water intake is restricted below normal. The arm of the T in which escape is possible is alternated from trial to trial. Two levels of problem solving are evaluated: an animal can minimize escape time during a series of trials by alternating its responses, i.e., 100% reinforcement; alternatively, it may choose the same alley on each trial, which results in only 50% reinforcement. The time to make the decision and the total time are automatically recorded. We have demonstrated the sensitivity of the method to hypofunctioning of the cholinergic neurotransmitter system, an analogy to behavioral changes accompanying progressive degenerative dementia. Two effects of the hypocholinergic state were especially notable: animals in this state have significantly greater difficulty in shifting from the "primitive" position habit to the more complex alternation solution, and preliminary experiments suggest that certain pharmacological treatments may be effective in overcoming this deficiency.

Value of non-invasive continuous blood pressure monitoring in the detection of carotid sinus hypersensitivity.

A patient with recurrent episodes of dizziness and blackouts is described. Detailed cardiac and neurological investigations were normal. Autonomic assessment excluded postural hypotension and confirmed normal sympathetic vasoconstrictor function. Cardiac parasympathetic function in response to deep breathing, hyperventilation and ocular pressure was normal. Left carotid sinus massage only reproducibly lowered blood pressure with minimal change in heart rate. This occurred mainly during head-up tilt. The fall in blood pressure was not affected by the muscarinic blocker atropine, or the peptide release inhibitor, octreotide. A diagnosis of left carotid sinus hypersensitivity of the vasodepressor variety was made. Left carotid sinus denervation was performed. This successfully prevented further episodes of dizziness and blackouts. The ability to measure beat-to-beat blood pressure non-invasively was of particular importance in diagnosis, and in the assessment of management options in this patient.