Exploring rehabilitation potential in older people living with frailty: a qualitative focus group study.

BACKGROUND: Rehabilitation interventions are frequently cited as key in supporting frail older people's recovery following periods of decompensation and acute ill-health. Clinicians are required to make decisions about a patient's potential to respond to rehabilitation. 'Rehabilitation potential' decisions can determine access to services. In acute settings clinicians have limited time to assess and work with patients, families and carers. The complexities of ageing, recovery, rehabilitation and frailty may not be fully appreciated. This study aimed to explore multiple perspectives of the concept of rehabilitation potential and how it is assessed in older people living with frailty in the acute healthcare setting. METHODS: Five focus groups with a purposive sample of 28 participants which included clinicians and members of the public were conducted. Analysis comprised a thematic approach using the Framework method. RESULTS: Rehabilitation potential was found to encapsulate a complex decision-making process where clinicians judged an individual's ability to benefit from and participate in targeted rehabilitation. They asked, "Will it work?", "Is it wanted?" and "Is it available?" In order to predict who would benefit from rehabilitation interventions, clinicians assessed a range of holistic clinical and non-clinical factors. An iterative approach to assessment delivered by a multi-disciplinary team, centred around patient and carer needs and wants was needed to accommodate complexity. Participants believed that everyone had some form of potential but this was dependent on availability of rehabilitation resources and conceptualisations of frailty and rehabilitation. Tensions between iterative approaches to rehabilitation potential assessment and the realities of rapid decision making in the acute hospital setting were found. CONCLUSION: Rehabilitation potential decisions involve a complex process of multidisciplinary decision-making and prognostication on the likely outcome and benefit from rehabilitation programmes. These findings lay the foundation for developing structured approaches to rehabilitation potential decision making tools and guidance.

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging.

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat.

Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population.

Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation.

Application of a computational model of vagus nerve stimulation.

OBJECTIVES: The most widely used and studied neurostimulation procedure for medically refractory epilepsy is vagus nerve stimulation (VNS) Therapy. The goal of this study was to develop a computational model for improved understanding of the anatomy and neurophysiology of the vagus nerve as it pertains to the principles of electrical stimulation, aiming to provide clinicians with a systematic and rational understanding of VNS Therapy. MATERIALS AND METHODS: Computational modeling allows the study of electrical stimulation of peripheral nerves. We used finite element electric field models of the vagus nerve with VNS Therapy electrodes to calculate the voltage field for several output currents and studied the effects of two programmable parameters (output current and pulse width) on optimal fiber activation. RESULTS: The mathematical models correlated well with strength-duration curves constructed from actual patient data. In addition, digital constructs of chronic versus acute implant models demonstrated that at a given pulse width and current combination, presence of a 110-µm fibrotic tissue can decrease fiber activation by 50%. Based on our findings, a range of output current settings between 0.75 and 1.75 mA with pulse width settings of 250 or 500 µs may result in optimal stimulation. CONCLUSIONS: The modeling illustrates how to achieve full or nearly full activation of the myelinated fibers of the vagus nerve through output current and pulse width settings. This knowledge will enable clinicians to apply these principles for optimal vagus nerve activation and proceed to adjust duty cycle and frequency to achieve effectiveness.

EAC-1A: A novel large-volume lunar regolith simulant.

The European Astronaut Centre (EAC) is currently constructing the European Lunar Exploration Laboratory (LUNA), a large training and operations facility to be located adjacent to EAC at the DLR (German Aerospace Centre) campus in Cologne, Germany. With an estimated representative lunar testbed area of approximately 660 m2, a large volume of lunar regolith simulant material is needed for this purpose. In this study, a basanitic sandy silt from a quarry located in the Siebengebirge Volcanic Field is evaluated as a large-volume source of material. The focus of this project has been to conduct a physical and chemical characterisation of the fine-grained material to be used in LUNA; the European Astronaut Centre lunar regolith simulant 1 (EAC-1 A). The physical characterisation tests undertaken include sphericity, density measurements, cohesion and static angle of repose, with mineralogical investigations via petrographical analysis with optical microscope and SEM, XRF, XRD and DSC measurements. The results of the EAC-1A tests are compared to published data on existing widely used lunar regolith simulants, namely JSC-1A, JSC-2A, NU-LHT-3M, DNA and FJS-1.

A genomic-systems biology map for cardiovascular function.

With the draft sequence of the human genome available, there is a need to better define gene function in the context of systems biology. We studied 239 cardiovascular and renal phenotypes in 113 male rats derived from an F2 intercross and mapped 81 of these traits onto the genome. Aggregates of traits were identified on chromosomes 1, 2, 7, and 18. Systems biology was assessed by examining patterns of correlations ("physiological profiles") that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.

Vasopressin reduces cardiac function and augments cardiopulmonary baroreflex resistance increases in man.

We examined the effects of physiologic infusions of arginine vasopressin (AVP) on cardiovascular hemodynamics and on reflex responses initiated by decreasing cardiopulmonary baroreceptor stimulation (with lower body negative pressure) in 10 healthy, captopril-pretreated young men (19-27 yr). Their responses were compared with those of four volunteers given isosmotic infusion. Heart rate, stroke volume, blood pressure, and forearm blood flow were measured by electrocardiography, impedance cardiography, radial artery cannulation, and strain gauge plethysmography. Two 55-min infusions of AVP at rates of 0.15 and 0.40 ng/kg per min increased average plasma concentrations from control levels of 5 pg/ml to 18 and 36 pg/ml, respectively. These infusions resulted in progressive reductions of heart rate and cardiac output and increases of forearm and total peripheral resistance. Blood pressure increases were significant only during the larger AVP infusion rate. Lower body negative pressure provoked reflex increases of total peripheral resistance. These increases were enhanced 60% during AVP infusion compared with increases during control (pre-AVP). Baseline measurements and reflex responses were unchanged by isosmotic infusions. These results demonstrate that AVP has profound effects on cardiovascular function and augments cardiopulmonary baroreflex-mediated increases of peripheral resistance in man.

Controlling wettability of PECVD-deposited dual organosilicon/carboxylic acid films to influence DNA hybridisation assay efficiency.

Herein, plasma polymerisation of a dual-layer tetraethyl orthosilicate (TEOS) and acrylic acid (AA) film under a specific recipe is performed. Newly deposited films are found to retain a weakly-bound soft layer of partially polymerised acrylic acid (wbAA), which can be ultimately removed by washing. However, when on the surface, this soft layer is shown to be influential in manipulating the properties of a robust covalently-bound AA (cbAA) underlayer when treated appropriately. Specifically, treatment of the as-deposited dual-layer TEOS/AA films via timed incubation in a humidity-controlled environment results in changes in the water contact angle (WCA) of the cbAA, and ultimately the surface of the TEOS/AA, enabling tuning of the wettability of the acrylic acid layer. Through the use of a controlled incubation environment of the TEOS/AA, followed by washing, we have demonstrated that carboxylic-acid containing surfaces with a WCA between 85° and 10° can be routinely generated, using basic apparatus and simple methodology. Moreover, these surfaces not only retain their AA functionality, demonstrated by covalent-linking of amine-terminated single-stranded DNA, but also strongly inhibit non-specific binding of the DNA strands. The efficiency of these surfaces to be used in DNA direct-binding hybridisation assays has been demonstrated, with limits of detection of 1.11 and 1.66 nM being measured.

Nondestructive X-ray diffraction measurement of warpage in silicon dies embedded in integrated circuit packages.

Transmission X-ray diffraction imaging in both monochromatic and white beam section mode has been used to measure quantitatively the displacement and warpage stress in encapsulated silicon devices. The displacement dependence with position on the die was found to agree well with that predicted from a simple model of warpage stress. For uQFN microcontrollers, glued only at the corners, the measured misorientation contours are consistent with those predicted using finite element analysis. The absolute displacement, measured along a line through the die centre, was comparable to that reported independently by high-resolution X-ray diffraction and optical interferometry of similar samples. It is demonstrated that the precision is greater than the spread of values found in randomly selected batches of commercial devices, making the techniques viable for industrial inspection purposes.

Cicada Wing Surface Topography: An Investigation into the Bactericidal Properties of Nanostructural Features.

Recently, the surface of the wings of the Psaltoda claripennis cicada species has been shown to possess bactericidal properties and it has been suggested that the nanostructure present on the wings was responsible for the bacterial death. We have studied the surface-based nanostructure and bactericidal activity of the wings of three different cicadas (Megapomponia intermedia, Ayuthia spectabile and Cryptotympana aguila) in order to correlate the relationship between the observed surface topographical features and their bactericidal properties. Atomic force microscopy and scanning electron microscopy performed in this study revealed that the tested wing species contained a highly uniform, nanopillar structure on the surface. The bactericidal properties of the cicada wings were investigated by assessing the viability of autofluorescent Pseudomonas fluorescens cells following static adhesion assays and targeted dead/live fluorescence staining through direct microscopic counting methods. These experiments revealed a 20-25% bacterial surface coverage on all tested wing species; however, significant bactericidal properties were observed in the M. intermedia and C. aguila species as revealed by the high dead:live cell ratio on their surfaces. The combined results suggest a strong correlation between the bactericidal properties of the wings and the scale of the nanotopography present on the different wing surfaces.

William Heberden revisited: postprandial angina-interval between food and exercise and meal composition are important determinants of time to onset of ischemia and maximal exercise tolerance.

OBJECTIVES: This study aimed to explore the hemodynamic responses to ingestion of meals of different composition in patients with chronic stable angina and to assess the effect of these meals on time to onset of > 1-mm ST segment depression and limiting angina pectoris during exercise. BACKGROUND: To our knowledge, no study has assessed the effect of meal composition and timing of exercise in patients with coronary artery disease. METHODS: Fifteen patients with chronic stable angina visited our laboratory in the fasted state on three occasions. Measurements of cardiac output, heart rate and blood pressure were taken while patients were standing. A modified Bruce exercise test was then carried out, during which time to onset of > 1-mm ST segment depression and limiting chest pain were recorded. Patients then ate a 2.5-MJ high fat or high carbohydrate meal; on the third occasion, no meal was taken. At 30 min and 1 h after eating the meals, rest hemodynamic measurements and exercise tests were repeated. RESULTS: The high fat meal did not affect exercise variables, whereas the high carbohydrate meal resulted in a reduction in time to onset of ST segment depression of 74.4 +/- 22.2 s (mean +/- SEM) during exercise at 30 min (p < 0.01), and at both 30 and 60 min after the high carbohydrate meal, limiting chest pain occurred 50 to 90 s earlier than when patients fasted (p < 0.01). CONCLUSIONS: One hour after a high carbohydrate meal, the onset of angina during exercise occurs earlier than in the fasted state. Despite similar hemodynamic adjustments, a high fat meal does not affect exercise time.

Hemodynamic effects of infused arginine vasopressin in congestive heart failure.

The hemodynamic effects of exogenously administered arginine vasopressin were assessed in 11 patients with chronic congestive heart failure. Infusion rates of 0.1 to 0.8 pmol/kg per min increased plasma arginine vasopressin from 6.5 +/- 2.7 (SD) pg/ml at control to 63 +/- 39 pg/ml at the highest infusion rate. There were progressive decreases in cardiac output and stroke volume, with increases in systemic vascular resistance and pulmonary capillary wedge pressure, but only minimal changes in heart rate and blood pressure. Changes in cardiac output, stroke volume and systemic resistance were evident from the first infusion rate, which increased plasma arginine vasopressin from 6.5 +/- 2.7 to 9.9 +/- 4.6 pg/ml. A paired analysis of baseline hemodynamic data with those measured during infusions producing an arginine vasopressin level averaging 15 +/- 2.6 pg/ml yielded the following changes: cardiac output decreased from 4.6 +/- 1.2 to 4.2 +/- 0.96 liters/min (p less than 0.01), stroke volume decreased from 60 +/- 19 to 54 +/- 16 ml (p less than 0.005) and systemic vascular resistance increased from 1,329 +/- 396 to 1,443 +/- 395 dynes X s X cm-5 (p = 0.01). Thus, small increases in circulating arginine vasopressin cause modest but significant adverse circulatory effects in patients with congestive heart failure. A fall in cardiac output, probably as a result of increased afterload, is seen at levels of arginine vasopressin within the basal range found in congestive heart failure. These data demonstrate that circulating arginine vasopressin in physiologic concentrations is capable of influencing hemodynamics in patients with congestive heart failure and suggest that therapy for this condition directed at inhibition of the vascular effect of arginine vasopressin may be potentially useful.

Impaired response of plasma vasopressin to orthostatic stress in patients with congestive heart failure.

Arginine vasopressin, a potent vasoconstrictor and regulator of body water, is frequently increased in the plasma of patients with congestive heart failure. Other neurohumoral control networks, such as the sympathetic nervous system and the renin-angiotensin system, also demonstrate increased activity in congestive heart failure, but fail to respond normally to physiologic stress, such as orthostatic tilt. To assess the response of plasma vasopressin to orthostasis in heart failure, vasopressin was measured before and at 10 and 45 minutes during passive upright tilt in 15 patients with congestive heart failure and their response was compared with that in 9 normal control subjects. Arginine vasopressin was measured by radioimmunoassay. In the normal subjects, plasma arginine vasopressin was 5.3 +/- 2.3 pg/ml at control, was unchanged at 10 minutes, but significantly increased to 7.0 +/- 2.5 pg/ml at 45 minutes (p less than 0.05). In contrast, patients with congestive heart failure showed no significant changes in arginine vasopressin levels from the control levels of 11.6 +/- 5.5 pg/ml. Both plasma norepinephrine and renin activity increased in the normal subjects, but failed to increase from higher baselines in patients with congestive heart failure. Thus, plasma arginine vasopressin, like plasma norepinephrine and renin activity, does not increase in response to upright tilt in patients with congestive heart failure. The explanation is not evident but could involve either abnormalities in reflex control of plasma vasopressin in congestive heart failure or in clearance of the hormone during orthostasis.

Depressor action of insulin on skeletal muscle vasculature: a novel mechanism for postprandial hypotension in the elderly.

OBJECTIVES: We sought to assess the role of insulin in postprandial blood pressure regulation in the elderly. BACKGROUND: Insulin is both a positive inotropic and chronotropic hormone that also vasodilates skeletal muscle vasculature. Insulin may thus mediate aspects of postprandial cardiovascular homeostasis. METHODS: Ten healthy elderly subjects were studied in the fasting state on three separate days. After baseline supine hemodynamic and neurohumoral measurements were taken (cardiac output and superior mesenteric artery blood flow were measured using Doppler ultrasound, and calf blood flow was measured using venous occlusion plethysmography), subjects ate on one occasion a 2.5-MJ high carbohydrate meal and on the other two occasions, an isoenergetic high fat meal. One high fat meal was accompanied by an insulin infusion reproducing the plasma insulin profile seen after a high carbohydrate meal while maintaining the glycemic profile seen after a high fat meal alone. After meal ingestion, measurements were repeated every 20 min for 2 h. RESULTS: After the three meals, there were similar increments in cardiac output and heart rate. After the high carbohydrate meal and high fat meal with insulin, mean arterial blood pressure fell by between 8 to 10 mm Hg, but did not change after the high fat meal. After the high carbohydrate meal and the high fat meal with insulin, calf vascular resistance did not change, whereas after the high fat meal, it increased by 15.5 +/- 4.4 U (mean +/- SEM). CONCLUSIONS: Insulin contributes to the failure of calf vasoconstriction seen after a high carbohydrate meal. By this vasodepressor action, insulin is at least in part responsible for the fall in blood pressure after a high carbohydrate meal.

Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure. The Milrinone Multicenter Trials Investigators.

We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they provide the only controlled data regarding the effect of oral milrinone on exercise capacity in patients receiving converting enzyme inhibitors. Of the 254 patients randomized, 140 completed one of the trials or reached an end point and are the basis of this report. In both trials, there was a clear trend for an increase in exercise capacity in the milrinone-treated patients (+26 +/- 8% vs. +5 +/- 7% in MIL-1077 and +11 +/- 5% vs. +2 +/- 4% in MIL-1078). Symptoms of congestive heart failure were decreased in one trial but not the other. Quality of life, as assessed by a questionnaire, was not effected in either trial. There was an increased incidence of adverse events in milrinone-treated patients. Adverse events related primarily to hypotension and vasodilation led to discontinuation of drug in 18 milrinone-treated patients vs. 1 placebo-treated patient. Milrinone had little or no proarrhythmic effect and cardiovascular deaths were distributed equally between the milrinone and placebo groups. These data suggest that when used in combination with a converting enzyme inhibitor, oral milrinone improves exercise capacity but is associated with a high incidence of adverse events that appear to be related to excessive vasodilation.

Mapping baroreceptor function to genome: a mathematical modeling approach.

To gain information about the genetic basis of a complex disease such as hypertension, blood pressure averages are often obtained and used as phenotypes in genetic mapping studies. In contrast, direct measurements of physiological regulatory mechanisms are not often obtained, due in large part to the time and expense required. As a result, little information about the genetic basis of physiological controlling mechanisms is available. Such information is important for disease diagnosis and treatment. In this article, we use a mathematical model of blood pressure to derive phenotypes related to the baroreceptor reflex, a short-term controller of blood pressure. The phenotypes are then used in a quantitative trait loci (QTL) mapping study to identify a potential genetic basis of this controller.

Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains.

To understand the genetic basis of pathways involved in the control of breathing, a large scale, high-throughput study using chromosomal substitution strains of rats is underway. Eight new consomic rat stains (SS-2(BN), SS-4(BN), SS-6(BN), SS-7(BN), SS-8(BN), SS-11(BN), SS-12(BN), SS-14(BN), SS-Y(BN)), containing one homozygous BN/NHsdMcwi (BN) chromosome on a background of SS/JrHsdMcwi (SS), were created by PhysGen (http://pga.mcw.edu) Program for Genomic Applications. Male and female rats were studied using standard plethysmography under control conditions and during acute hypoxia (inspired oxygen fraction = 0.12) and hypercapnia (inspired CO(2) fraction = 0.07). The rats were also studied during treadmill exercise. Both male and female BN rats had a significantly lower ventilatory response during 7% CO(2) compared with SS rats of the same gender. SS-6(BN) female rats had a significantly reduced ventilatory response, similar to BN rats due primarily to a reduced tidal volume. Male SS-6(BN) rats had a significantly reduced tidal volume response to hypercapnia but a slightly increased frequency response during hypercapnia. Gene(s) on the Y chromosome may play a role in this increased frequency response in the male rats because the SS-Y(BN) hypercapnic ventilatory response involves a significantly increased frequency response. Several chromosomal substitutions slightly altered the ventilatory responses to hypoxia and exercise. However, genes on chromosomes 6 and Y of those studied are of primary importance in aspects of ventilatory control currently studied.

Quantitative analysis of the acute response to haemorrhage of the renin-angiotensin-vasoconstrictor feedback loop in areflexic dogs.

The importance of the renin-angiotensin-vasoconstrictor system during haemorrhagic hypotension was quantitated in 44 areflexic dogs by determining the ability of the arterial pressure to recover following haemorrhage to 8.8 kPa (66 mm Hg). In 30 animals with intact kidneys, the arterial pressure following haemorrhage rose to a new steady-state level averaging 11.7 kPa (88 mm Hg), which represented 65.3 +/- 1.8 (SE) % compensation. In 18 nephrectomized animals only 24.4 +/- 1.5% compensation occurred. The system exhibited a relatively rapid time course for pressure compensation with the new steady state occurring 19.2 +/- 2.0 min after haemorrhage. Following reinfusion of blood the pressure returned to the pre-haemorrhage in 19.2 +/- 3.0 min. Arterial renin activity was significantly elevated following haemorrhage in the intact kidney group and unchanged in the anephric group. The arterial pressure compensation of two animals with intact kidneys was significantly reduced when the angiotensin-converting enzyme inhibitor (SQ 20881) was infused before the haemorrhage. The results are consistent with a renin-angiotensin-vasoconstrictor mechanism of arterial pressure compensation and indicate that this mechanism possesses sufficient gain and time response characteristics to play a homeostatically significatn role during haemorrhagic hypotension.

The effect of aspirin on peripheral haemodynamic changes following submaximal exercise in normal volunteers.

Eight normal healthy volunteers participated in a study to determine the effect of 1800 mg of aspirin on the peripheral haemodynamic changes that occur following upright exercise. Aspirin reduced the extent of calf hyperaemia (p less than 0.05) and accentuated the reduction in forearm blood flow (p less than 0.05) following exercise. It had no effect on either calf or forearm blood flow at rest. These results indicate that aspirin, possibly by inhibiting prostacyclin production, modifies the circulatory changes following upright exercise.

Effect of aspirin and indomethacin on exercise-induced changes in blood pressure and limb blood flow in normal volunteers.

To evaluate the possible role of prostaglandins in exercise-induced changes in blood pressure and limb blood flow we have compared the effects of aspirin and indomethacin in a double-blind placebo controlled study in a group of normal volunteers. Nine men undertook treadmill exercise after pretreatment with placebo, aspirin and indomethacin. Indomethacin caused a greater increase in systolic blood pressure during exercise than aspirin (p less than 0.05) and a smaller fall in diastolic pressure than either placebo or aspirin (p less than 0.02 and p less than 0.01). Compared with placebo both aspirin and indomethacin attenuated to a similar degree the increase in calf blood flow (p less than 0.05 and p less than 0.03) and the changes in forearm blood flow following exercise. These results suggest that although aspirin and indomethacin both inhibit prostaglandin production they have different effects on exercise-induced changes in blood pressure. They have, however, similar effects on limb blood flow.