Distension In Humans Research Articles

Baroreflex responses to limb venous distension in humans.

The venous distension reflex (VDR) is a pressor response evoked by peripheral venous distension and accompanied by increased muscle sympathetic nerve activity (MSNA). The effects of venous distension on the baroreflex, an important modulator of blood pressure (BP), have not been examined. The purpose of this study was to examine the effect of the VDR on baroreflex sensitivity (BRS). We hypothesized that the VDR will increase the sympathetic BRS (SBRS). Beat-by-beat heart rate (HR), BP, and MSNA were recorded in 16 female and 19 male young healthy subjects. To induce venous distension, normal saline equivalent to 5% of the forearm volume was infused into the veins of the occluded forearm. SBRS was assessed from the relationship between diastolic BP and MSNA during spontaneous BP variations. Cardiovagal BRS (CBRS) was assessed with the sequence technique. Venous distension evoked significant increases in BP and MSNA. Compared with baseline, during the maximal VDR response period, SBRS was significantly increased (-3.1 ± 1.5 to -4.5 ± 1.6 bursts·100 heartbeats-1·mmHg-1, P < 0.01) and CBRS was significantly decreased (16.6 ± 5.4 to 13.8 ± 6.1 ms·mmHg-1, P < 0.01). No sex differences were observed in the effect of the VDR on SBRS or CBRS. These results indicate that in addition to its pressor effect, the VDR altered both SBRS and CBRS. We speculate that these changes in baroreflex function contribute to the modulation of MSNA and BP during limb venous distension.

Abstract 13889: Impact Of Acute Hypoxia On Left Ventricular Relaxation Time In Healthy Men

Introduction: The oxygen-dependence of myocardial contractility is known but it is not the case for ventricular distension in humans. It has been shown that acute ischemia causes incomplete and retarded relaxation through the decrease in intracellular pH and ATP content. Purpose: to verify whether hypoxemia changes the left ventricular relaxation time (LVRT). Methods: Overall, 37 physically active normotensive men (age 19-42 years, 20.4±2.3 yrs., M±SD) constituted the study sample. The LVRT was derived from aortic pulse wave analysis (SphygmoCor) and measured as difference between the end of systole (ejection duration point, ED, corresponding to the closure of aortic valve) and the time of peak pressure (T1), generated by LV in the aortic root and corresponding to the first incisura [LVRT,%=(ED-T1)/length of cardiac cycle*100]. Subjects inhaled hypoxic mixture with 10%O2 over 10 min for mean blood SpO2 of 80%. Associations were assessed by partial correlation (age, SBP=const.), multiple linear regression analyses (GLM option in SPSS), and t-test for dependent samples. Results: At baseline, the longer length of LVR was associated with lower end systolic blood pressure (r=-0.56, p&lt;0.001). The regression model combining heart rate, augmentation pressure, and aortic-to-radial pulse pressure amplification explained 98.6% of total LVRT variation with significant effects of all covariates. Hypoxia increased LVRT from 19.0±2.8% to 23.1±4.2%, p&lt;0.001. The response of LVRT to hypoxic exposure (range for Δ, -0.7%, +9.1%) was directly correlated with the extent of blood oxygen desaturation (r=0.53, p=0.016). Conclusion: The results show that cardiomyocytes retard their relaxation in hypoxic conditions. Cardiomyocytes happened to be quite sensitive to hypoxemia since even 10-min hypoxia was sufficient for elongation of the ventricular relaxation.

Cyclooxygenase Inhibition Attenuates the Muscle Sympathetic Nerve Activity Responses to Venous Distension in Humans

We have shown that venous distension induced by saline infusion into veins of an arterially occluded arm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans. Recently, Yamauchi and colleagues examined this venous distension reflex in rats and showed that cyclooxygenase blockade with indomethacin attenuated the reflex pressor response. We hypothesized that blockade of prostaglandin synthesis could attenuate MSNA responses to venous distension in humans. BP (Finapres), heart rate, and MSNA (microneurography) were assessed in 11 young healthy subjects during infusion of 6 mg ketorolac tromethamine in 40 ml saline into veins of an arterially occluded arm. In the second experiment, the same amount of saline was infused (control trial). MSNA significantly rose towards to the end of infusion of saline (18.1±2.1 to 27.0±2.7 bursts/min, P&lt;0.01), while no significant change was observed in the ketorolac trial (19.0±2.2 to 22.7±3.2 bursts/min, P=0.77). BP significantly rose towards to the end of infusion in the both trials, and the BP response in ketorolac trial tended to be less than that in saline trial (P=0.07). These observations indicate that blockade of prostaglandin synthesis may attenuate MSNA and BP responses to distension of veins, and suggest that prostaglandins may contribute to the venous distension reflex.

Distension of central great vein decreases sympathetic outflow in humans

Classic canine studies suggest that central great vein distension evokes an autonomic reflex tachycardia (Bainbridge reflex). It is unclear whether central venous distension in humans is a necessary and sufficient stimulus to evoke a reflex increase in heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA). Prior work from our laboratory suggests that limb venous distension evokes a reflex increase in BP and MSNA in humans. We hypothesized that in humans, compared with the limb venous distension, inferior vena cava (IVC) distension would evoke a less prominent increase in HR and MSNA. IVC distension (monitored with ultrasonography) was induced by two methods: 1) head-down tilt (HDT, N = 13); and 2) lower-body positive pressure (LBPP, N = 10). Two minutes of HDT induced IVC distension (Δ2.6 ± 0.2 mm, P < 0.001, ~27% in cross-sectional area), slightly increased mean BP (Δ2.3 ± 0.7 mmHg, P = 0.005), decreased MSNA (Δ5.2 ± 0.8 bursts/min, P < 0.001, N = 10), and did not alter HR (P = 0.37). LBPP induced similar IVC distension, increased BP (Δ2.0 ± 0.7 mmHg, P < 0.01), and did not alter HR (P = 0.34). Thus central venous distension leads to a rapid increase in BP and a subsequent fall in MSNA. Central venous distension does not evoke either bradycardia or tachycardia in humans. The absence of a baroreflex-mediated bradycardia suggests that the Bainbridge reflex is engaged. Clearly, this reflex differs from the powerful sympathoexcitation peripheral venous distension reflex described in humans.

Effects of Preceding Stimulation on Brain Activation in Response to Colonic Distention in Humans

It has been suggested that the pattern of distension (moderate following mild and vice versa) might influence brain activation and the experience of hypersensitivity, offset analgesia, and anticipation. Nevertheless, how the pattern of stimulation affects sensitization and/or desensitization to visceral stimulation remains unknown. In 45 nonclinical healthy participants (12 women, 33 men; 20-26 years old), brain processing of visceral sensation induced by colonic distension was examined using H2(15)O positron emission tomography. Subjective feelings regarding the stimuli were also measured. The descending colon was stimulated using six patterns of three bag pressures (0, 20, and 40 mm Hg). To evaluate the neural sensitization to visceral stimulation arising from the precedence effect, the effects of a 20- or 40-mm Hg distention after a sham or 20- or 40-mm Hg distension were analyzed using statistical parametric mapping. The level of significance was set at a voxelwise level of p < .0001, with cluster extent sizes of k > 50. The midbrain, insula, and cerebellum, were more strongly activated by a 20-mm Hg distension with a preceding 40-mm Hg distention than by a 20-mm Hg distention without a preceding stimulation (p < .0001). Conversely, a sham stimulation after the experience of an intense stimulation activated the midcingulate cortex, compared with a sham stimulation without the experience of actual visceral stimulation (p < .0001). By directly comparing different patterns of visceral stimuli, preceding visceral stimuli may affect neural sensitization and/or desensitization in humans, including elevated midbrain, insula, and midcingulate cortex.

Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention

Background and aimsDetermining the gene that plays a key role in brain–gut interactions is a crucial step for clarifying the pathophysiology of irritable bowel syndrome (IBS). We previously reported that the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is related to anxiety in subjects with IBS. The amygdala is more activated during fearful face recognition in individuals with the s allele of 5-HTTLPR. Here, we tested our hypothesis that 5-HTTLPR differentially activates brain regions with colorectal distention in humans. MethodsWe enrolled 28 subjects without any organic disease. The study was approved by the Ethics Committee and all subjects gave written informed consent. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Age, sex, diagnosis-matched individuals with the s/s genotype (n=14) and individuals with the l allele (genotypes l/s, l/l, l/extra-l, n=14) were compared. A barostat bag was inserted to the colorectum and was intermittently inflated with no (0 mm Hg), mild (20 mm Hg), or intense (40 mm Hg) stimulation on a random order. Radioactive H2[15-O] saline was injected at bag inflation and then positron emission tomography was performed. Changes in rCBF were analyzed using statistical parametric mapping. ResultsIndividuals with the s/s genotype showed a significantly larger increase in rCBF by colorectal distention from 0 mm Hg to 40 mm Hg than individuals with the l allele. The significantly more activated brain regions in individuals with the s/s genotype were the left anterior cingulate cortex and right parahippocampal gyrus (p<0.0001). The increase in rCBF by colorectal distention of 20 mm Hg compared with 0 mm Hg was significantly larger in the left orbitofrontal cortex of individuals with the s/s genotype than that of individuals with the l allele (p<0.0001). ConclusionThese data suggest that individuals with a weak function of serotonin transporter respond to gut signals more in emotion-regulating brain regions. Functional gene polymorphism may partially predict the individual effect of a selective serotonin reuptake inhibitor on visceral pain.

Adenosine modulates oesophageal sensorimotor function in humans

Background and aims:Adenosine mediates somatic and visceral pain, but its effects on gut visceral nociception are unknown. The aim of the present study was to test the hypothesis that adenosine...

Supraspinal control of external anal sphincter motility: effects of vesical distension in humans and cats

A pontine centre located near the micturition centre controlling external anal sphincter (EAS) motility via noradrenergic neurones has been described in cats. The aim of this study was to determine (i) whether a similar centre controls EAS motility in humans and (ii) whether this centre is involved in vesico-sphincteric reflexes in cats and humans. The effects of an alpha-1-adrenoceptor antagonist (nicergoline) and those of vesical distension on the electrical activity of the EAS were studied in paraplegic and non-paraplegic volunteers. The effects of vesical distension by injecting saline at physiological levels on the responses of the EAS to pudendal nerve stimulation were investigated in intact cats and cats with nerve sections. In non-paraplegic subjects, nicergoline and vesical distension abolished the activity of the EAS. These effects were no longer observed in paraplegic patients. In cats, vesical distension inhibited the reflex response of the EAS to pudendal nerve stimulation. This vesico-sphincteric reflex, which was no longer observed in spinal animals, persisted after nicergoline injection. These findings indicate that in humans, there exists a supra-spinal centre facilitating the tonic activity of the EAS via noradrenergic neurones not involved in the inhibitory vesico-sphincteric reflex.

Basal NO Locally Modulates Human Iliac Artery Function In Vivo

We demonstrated previously that endogenous NO influences large-artery distensibility in the ovine hindlimb. However, the role of basal NO in larger human conduit arteries is controversial. The aim of this study was to investigate whether basal production of NO, acting locally, influences iliac artery distensibility in humans. Distensibility was assessed by intra-arterial measurement of the pulse wave velocity. Eighteen subjects, free of significant coronary or iliac artery disease, were studied after diagnostic cardiac catheterization. Simultaneous pressure waveforms were recorded with a high-fidelity dual-pressure sensing catheter, placed in the common iliac artery during intra-arterial infusion of saline (baseline), glyceryl trinitrate (4 nmol/min), or NG-monomethyl-L-arginine (8 and 16 micromol/min). Drugs were infused proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath, to control for any reflex changes in flow or sympathetic activation. Velocity was calculated using the foot-to-foot methodology. Six subjects received glyceryl trinitrate and 12 NG-monomethyl-L-arginine. There was no change in velocity after infusion of glyceryl trinitrate or NG-monomethyl-L-arginine via the sheath. However, infusion of glyceryl trinitrate via the catheter significantly reduced velocity by 31.43+/-5.80% (mean+/-SEM; P<0.01; P=0.02 for comparison). Likewise, infusion of the highest dose of NG-monomethyl-L-arginine via the catheter significantly increased velocity by 27.25+/-8.20% (P=0.001; P=0.02 for comparison). Importantly, there was no change in mean arterial blood pressure throughout the studies. These data indicate that under resting conditions, local NO production modulates human iliac artery distensibility and that exogenous NO increases arterial distensibility.

Distensibility of the normal human lung circulation during exercise

Increasing pulmonary arterial (Ppa) and wedge (Pw) pressures at high flow (Q) during exercise could distend the thin-walled vessels. A mechanical descriptor of vascular distension, the distensibility (alpha, fractional diameter change/mmHg pressure), has been reported to be approximately 0.02 for isolated large and small arteries, i.e., a 2% change in diameter per millimeter mercury pressure. In this review we used a pulmonary hemodynamic model to estimate alpha for data from exercising humans to determine whether interpretable results might be obtained. In 59 normal sea level subjects having published measurements of Ppa and Pw over a range of Q, we found values of alpha (0.02 +/- 0.002) giving calculated Ppa, which matched measured Ppa to within 1.3 +/- 0.1 (SE) mmHg. When subjects were exposed to chronic hypoxia (n = 6, in Operation Everest II), alpha decreased (0.022 +/- 0.002 vs. 0.008 +/- 0.001, P < 0.05), but when subjects were exposed to acute hypoxia (Duke chamber study, n = 8), alpha did not decrease (0.014 +/- 0.002 vs. 0.012 +/- 0.002, P = not significant). Values of alpha tended to decrease with age in men >60 yr. Thus at rest and during exercise, normal values of alpha in young persons were similar to those measured in vitro, and the values decreased in chronic hypoxia and with aging where vascular remodeling or vascular wall stiffening was expected. We propose that the estimation of pulmonary vascular distensibility in humans may be a useful descriptor of pulmonary hemodynamics.

Regional brain activation during proximal stomach distention in humans: A positron emission tomography study

Hypersensitivity to proximal gastric distention due to abnormal central nervous system processing of visceral stimuli has been suggested as a possible underlying pathophysiologic mechanism in functional dyspepsia. However, the cortical regions activated by distention of the proximal stomach have not been identified. The aim of this study was to investigate regional brain activation during painful and nonpainful proximal gastric distention in humans. Positron emission tomography of the brain was performed in 11 healthy volunteers during 4 conditions: (1) no distention and isobaric distention to the individual thresholds for (2) first, (3) marked, and (4) unpleasant sensation. Data were analyzed using statistical parametric mapping. During maximal distention relative to baseline, significant (P corrected <.05) regional brain activation occurred in the left and right gyrus postcentralis (Brodmann area [BA] 43), the left gyrus temporalis superior (BA 38), the right gyrus frontalis inferior (BA 47, orbitofrontal cortex), the right midanterior cingulate gyrus (BA 24), the right anterior insula, and the left cerebellar hemisphere. These areas showed a progressive increase in activation with increasing intensity of the distending stimulus. We found evidence for a neuronal network processing distention stimuli of the proximal stomach that is overall consistent with the "visceral stimulation network" described in the literature. In addition, we found activation of the orbitofrontal cortex, confirming its role as a convergence zone for processing of food-related stimuli and regulation of hunger, appetite, satiety, and food intake. We found no evidence for a functional neuroanatomic divergence in the processing of noxious and innocuous gastric stimuli.

Effects of Heart Rate Changes on Arterial Distensibility in Humans

To the Editor: Dependence of arterial stiffness on heart rate, claimed by Giannattasio et al,1 runs counter to classic studies, which were previously discussed in relation to conflicting data obtained with one method used to measure aortic pulse wave velocity.2 There is a potential flaw in the method applied by Giannattasio et al in their determination of carotid and radial artery distensibility at different heart rates. They measured diameter change of the target artery, but pressure pulsation at a distal site (brachial pressure for carotid, finger pressure for radial artery). Errors inherent in distal pressure measurement have been stressed in a recent consensus document3 but were considered by authors1 to be minimal. We disagree. In similar studies by Wilkinson et al,4 there was an …

Arterial distensibility in humans. Modulating mechanisms, alterations in diseases and effects of treatment.

Reduction of large artery distensibility has several adverse consequences for the cardiovascular system. This paper reviews the evidence obtained by measuring distensibility through quantification of changes in arterial diameter versus blood pressure changes at large elastic and middle size muscle artery sites. Evidence is available that arterial distensibility is reduced in conditions as varied as hypercholesterolemia, hypertension, diabetes and congestive heart failure. In some conditions (e.g. hypertension) the alterations are not uniformly distributed in arteries of different structure and size whereas in others (e.g. diabetes and heart failure) they are widespread. In diabetes evidence is available that distensibility changes occur early in the course of the disease. Evidence is also available that in all above conditions treatment can improve arterial distensibility thereby reversing the initial abnormality. This appears to be due to a variable combination of structural and functional factors. Technical ability to determine their precise role in distensibility changes in humans is limited, however.

Nitric Oxide and Cardiac Contractility in Human Heart Failure

The free radical gas nitric oxide (NO) is produced by 3 isoforms of nitric oxide synthase (NOS). All of them are present in the heart: NOS1 (nNOS, “neuronal” NOS) has been detected in cardiac conduction tissue and intracardiac neurons; NOS2 (iNOS, “cytokine-inducible” NOS) can be expressed by virtually all cells in the heart, often in conjunction with the expression of inflammatory cytokines; and finally, NOS3 (eNOS, “endothelial-constitutive” NOS) is expressed in coronary endothelium, endocardium, and cardiac myocytes. NOS3 regulates the tone of vascular smooth muscle cells; the permeability and platelet adhesion of endothelial cells; and the receptor-effector coupling, energetics, contractility, and apoptosis of cardiomyocytes.1,2 Since the original demonstration of myocardial NOS2 activity in idiopathic dilated cardiomyopathy,3 a negative inotropic effect of NO frequently was hypothesized to contribute to the depressed contractile function of failing myocardium. This hypothesis was inspired by the simultaneous publication of experimental results that showed a depressed contractile response of isolated cardiomyocytes to β-adrenergic agonists after NOS2 induction by lipopolysaccharides.4 See p 2318 To further explore this depressant action of NO on myocardial contractility, numerous experimental and clinical studies were performed, but they yielded apparently conflicting results on the inotropic effect of NO from either endogenous or pharmacological sources.2 As reported in this issue of Circulation , Cotton et al5 tackled the question of the inotropic action of NO by measuring left ventricular (LV) performance in normal control subjects and in patients with dilated cardiomyopathy during intracoronary infusion of the NOS inhibitor NG-monomethyl-l-arginine (L-NMMA). During L-NMMA infusion, Cotton et al5 observed a modest drop (14%) in LV dP/dtmax in the control group and no change in LV dP/dtmax in the cardiomyopathy group, despite myocardial expression of NOS2 in their patients. They concluded that the small …

Comparison of aortic arch and carotid sinus distensibility in humans—relation to baroreflex sensitivity

We compared aortic arch (AA) and carotid sinus (CS) distensibility, and determined the relationship between baroreflex sensitivity (BRS) and distensibility coefficients of AA and CS (DC AA and DC CS, respectively). In 47 healthy 19–71-year-old subjects, AA and CS end-diastolic diameter ( D) and pulsatile distension (Δ D) was measured with ultrasound and arterial pressure by sphygmomanometer and Finapres. DC was calculated as 2Δ D/( D×Δ P), where Δ P is the pulse pressure. BRS was determined by the sequence method. Data are given as mean±S.D.; significance was set at p<0.05. DC AA and DC CS were linearly related across subjects ( r=0.80, p<0.001). No difference between DC AA and DC CS (3.8±1.4×10 −3 and 4.2±2.2×10 −3 mm Hg −1, respectively) was found for all subjects (paired t-test). However, at ages <35 years, DC CS exceeded DC AA, whereas this relation was reversed at ages >35 years. Age accounted for 53% of variability in DC AA and 73% of variability in DC CS. BRS was related to DC (linear regression), with the BRS–DC AA relation being steeper and closer ( r=0.73, p<0.001) than the BRS–DC CS relation ( r=0.54, p<0.05). It is suggested that aortic baroreceptors may have a dominant role in heart rate control.

A simplified approach for real-time detection of arterial wall velocity and distension.

Arterial stiffness is known to increase with age and with many vascular diseases, but its noninvasive assessment in patients still represents a difficult task. The measurement of diameter change during the cardiac cycle (distension) has been proposed as a means to estimate arterial compliance and stiffness. Therefore, we have developed a simple PC-based device and algorithm for noninvasive quantification of vessel wall motion and diameter change in humans. This goal is achieved in real-time by processing the base-band signals from a commercial ultrasound Doppler system. Real-time operation is of crucial importance, because it allows a rapid achievement of optimal measurement conditions. The system was evaluated in a laboratory using a string phantom and was tested on the carotid arteries of 10 volunteers. Wall velocities from 0.05 to 600 mm/s and displacements lower than 2 microns were detected with phantoms. The measured carotid diameter change in the volunteers ranged from 7.5 to 11.8% (mean = 9.8%) and agrees closely with values reported in the literature. The difference between values taken one hour apart ranged from 0.2 to 0.5%. We conclude that the new system provides rapid, accurate, and repeatable measurements of vessel distension in humans.

Endogenous GLP-1(7-36)amide (GLP-1) reduces perception of gastric distention in humans

Endogenous GLP-1(7-36)amide (GLP-1) reduces perception of gastric distention in humans

Endogenous GLP-1(7-36)amide (GLP-1) reduces perception of gastric distention in humans

Endogenous GLP-1(7-36)amide (GLP-1) reduces perception of gastric distention in humans

Prolonged intragastric distention in humans induces phasic gastric contractions during fasting and after a meal

Prolonged intragastric distention in humans induces phasic gastric contractions during fasting and after a meal

Effect of physical activity on the distensibility of the aortic wall in healthy males.

To study the effect of physical activity level on the distensibility of the human aortic wall, aortic pulse wave velocity (APWV) was estimated in 139 healthy male subjects (19-67 years) and was related to the energy expenditure by habitual physical exercise (physical activity index: PAI), which was evaluated by a 7-day total activity recall. The subjects consisted of 56 fun runners (runner group) and 83 general subjects, who were divided into 25 active subjects (active group: PAI > or = 1,500 kcal/week) and 58 sedentary subjects (sedentary group: PAI < 1,500 kcal/week). The APWV index (APWVI: standardized APWV by the diastolic blood pressure) was found to be positively correlated with age and was negatively correlated with PAI. The age-adjusted APWVI of the runner group was significantly lower than that of the active and sedentary groups. The age-adjusted APWVI was also significantly lower in the active group than in the sedentary group. These results suggest that increased physical activity may retard the age-dependent loss of arterial distensibility in humans, in proportion to the amount and/or intensity of exercise.