Utilizing intraluminal pressure differences to predict esophageal bolus flow dynamics

Successful esophageal emptying depends on the generation of a sustained intrabolus pressure (IBP) sufficient to overcome esophagogastric junction (EGJ) obstruction. Our aim was to develop a manometric analysis paradigm that describes the bolus driving pressure difference and the flow permissive time for esophageal bolus transit. Twenty normal subjects were studied with a 36-channel manometry assembly (1-cm spacing) during two 5- and one 10-ml barium swallows and concurrent fluoroscopy. Bolus domain pressure plots were generated by plotting bolus domain pressure (BDP) and EGJ relaxation pressure. BDP was defined as the pressure midway between the peristaltic ramp-up and the proximal margin of the EGJ. The flow permissive time was defined as the period where the BDP was > or = EGJ relaxation pressure. The mean BDP was 11.7 +/- 1.0 mmHg (SE), and the mean flow permissive time was 3.9 +/- 0.4 s for 5-ml swallows in normal controls. The mean BDP difference during flow was 4.0 +/- 1.0 mmHg. There was no significant difference in the fluoroscopic transit time and the flow permissive time calculated from the BDP plots (5 ml: fluoroscopy 3.4 +/- 0.2 s; BDP 3.9 +/- 0.4 s, P > 0.05). BDP plots provide a reliable measurement of IBP and its relationship with EGJ relaxation. The time available for flow can be readily delineated from this analysis, and the driving pressure responsible for flow can be accurately described and quantified. This may help predict abnormal bolus transit and the underlying mechanical properties of the EGJ.     

Middle cerebral artery blood velocity during a valsalva maneuver in the standing position.

Occasionally, lifting of a heavy weight leads to dizziness and even to fainting, suggesting that, especially in the standing position, expiratory straining compromises cerebral perfusion. In 10 subjects, the middle cerebral artery mean blood velocity (V(mean)) was evaluated during a Valsalva maneuver (mouth pressure 40 mmHg for 15 s) both in the supine and in the standing position. During standing, cardiac output decreased by 16 +/- 4 (SE) % (P < 0.05), and at the level of the brain mean arterial pressure (MAP) decreased from 89 +/- 2 to 78 +/- 3 mmHg (P < 0.05), as did V(mean) from 73 +/- 4 to 62 +/- 5 cm/s (P < 0.05). In both postures, the Valsalva maneuver increased central venous pressure by approximately 40 mmHg with a nadir in MAP and cardiac output that was most pronounced during standing (MAP: 65 +/- 6 vs. 87 +/- 3 mmHg; cardiac output: 37 +/- 3 vs. 57 +/- 4% of the resting value; P < 0.05). Also, V(mean) was lowest during the standing Valsalva maneuver (39 +/- 5 vs. 47 +/- 4 cm/s; P < 0.05). In healthy individuals, orthostasis induces an approximately 15% reduction in middle cerebral artery V(mean) that is exaggerated by a Valsalva maneuver performed with 40-mmHg mouth pressure to approximately 50% of supine rest.     

Impaired deglutitive EGJ relaxation in clinical esophageal manometry: a quantitative analysis of 400 patients and 75 controls

Assessing deglutitive esophagogastric junction (EGJ) relaxation is an essential focus of clinical manometry. Our aim was to apply automated algorithmic analyses to high-resolution manometry (HRM) studies to ascertain the optimal method for discriminating normal from abnormal deglutitive EGJ relaxation. All 473 subjects (73 controls) were studied with a 36-channel solid-state HRM assembly during water swallows. Patients were classified as: 1) achalasia, 2) postfundoplication, 3) nonachalasia with normal deglutitive EGJ relaxation, or 4) functional obstruction (preserved peristalsis with incomplete EGJ relaxation). Automated computer programs assessed the adequacy of EGJ relaxation by using progressively complex analysis routines to compensate for esophageal shortening, crural diaphragm contraction, and catheter movement, all potential confounders. The single-sensor method of assessing EGJ relaxation had a sensitivity of only 52% for detecting achalasia. Of the automated HRM analysis paradigms tested, the 4-s integrated relaxation pressure using a cutoff of 15 mmHg performed optimally with 98% sensitivity and 96% specificity in the detection of achalasia. We also identified a heterogeneous group of 26 patients with functional EGJ obstruction attributed to variant achalasia and other diverse pathology. Although further clinical experience will ultimately judge, it is our expectation that applying rigorous methodology such as described herein to the analysis of HRM studies will improve the consistency in the interpretation of clinical manometry and prove useful in guiding clinical management.     

Adding a radial dimension to the assessment of esophagogastric junction relaxation: validation studies of the 3D-eSleeve

High-resolution manometry (HRM) with esophageal pressure topography (EPT) allowed for the establishment of an objective quantitative measurement of esophagogastric junction (EGJ) relaxation, the integrated relaxation pressure (IRP). This study assessed whether or not a novel 3D-HRM assembly could improve on this measurement. Twenty-five normal subjects were studied with both a standard HRM assembly and a novel hybrid assembly (3D-HRM), including a 9.0 cm 3D-HRM segment composed of 96 radially dispersed independent pressure sensors. The standard IRP was computed using each assembly and compared with a novel paradigm, the 3D-IRP, an analysis premised on finding the axial maximum and radial minimum pressure at each sensor ring along the sleeve segment. Fourteen additional subjects underwent barium swallows with 3D-HRM and concurrent videofluoroscopy to compare the electronic sleeve (eSleeve) paradigm (circumferential average) to the 3D eSleeve paradigm (radial minimum) as a predictor of transphincteric flow. The 3D-IRP was significantly less than all other calculations of IRP with the upper limit of normal being 12 mmHg vs. 17 mmHg for the standard IRP. The sensitivity (0.78) and the specificity (0.88) of the 3D-eSleeve were also better than the standard eSleeve (0.55 and 0.85, respectively) for predicting flow permissive time verified fluoroscopically. The 3D-IRP and 3D-eSleeve calculated using the radial pressure minimum lowered the normative range of EGJ relaxation (upper limit of normal 12 mmHg) and yielded intraluminal pressure gradients that better correlated with bolus flow than did analysis paradigms based on circumferentially averaged pressure.     

Regulation of middle cerebral artery blood velocity during dynamic exercise in humans: influence of aging.

Although cerebral autoregulation (CA) appears well maintained during mild to moderate intensity dynamic exercise in young subjects, it is presently unclear how aging influences the regulation of cerebral blood flow during physical activity. Therefore, to address this question, middle cerebral artery blood velocity (MCAV), mean arterial pressure (MAP), and the partial pressure of arterial carbon dioxide (Pa(CO(2))) were assessed at rest and during steady-state cycling at 30% and 50% heart rate reserve (HRR) in 9 young (24 +/- 3 yr; mean +/- SD) and 10 older middle-aged (57 +/- 7 yr) subjects. Transfer function analysis between changes in MAP and mean MCAV (MCAV(mean)) in the low-frequency (LF) range were used to assess dynamic CA. No age-group differences were found in Pa(CO(2)) at rest or during cycling. Exercise-induced increases in MAP were greater in older subjects, while changes in MCAV(mean) were similar between groups. The cerebral vascular conductance index (MCAV(mean)/MAP) was not different at rest (young 0.66 +/- 0.04 cm x s(-1) x mmHg(-1) vs. older 0.67 +/- 0.03 cm x s(-1) x mmHg(-1); mean +/- SE) or during 30% HRR cycling between groups but was reduced in older subjects during 50% HRR cycling (young 0.67 +/- 0.03 cm x s(-1) x mmHg(-1) vs. older 0.56 +/- 0.02 cm x s(-1) x mmHg(-1); P < 0.05). LF transfer function gain and phase between MAP and MCAV(mean) was not different between groups at rest (LF gain: young 0.95 +/- 0.05 cm x s(-1) x mmHg(-1) vs. older 0.88 +/- 0.06 cm x s(-1) x mmHg(-1); P > 0.05) or during exercise (LF gain: young 0.80 +/- 0.05 cm x s(-1) x mmHg(-1) vs. older 0.72 +/- 0.07 cm x s(-1) x mmHg(-1) at 50% HRR; P > 0.05). We conclude that despite greater increases in MAP, the regulation of MCAV(mean) is well maintained during dynamic exercise in healthy older middle-aged subjects.     

Deglutitive upper esophageal sphincter relaxation: a study of 75 volunteer subjects using solid-state high-resolution manometry

This study aimed to use a novel high-resolution manometry (HRM) system to establish normative values for deglutitive upper esophageal sphincter (UES) relaxation. Seventy-five asymptomatic controls were studied. A solid-state HRM assembly with 36 circumferential sensors spaced 1 cm apart was positioned to record from the hypopharynx to the stomach. Subjects performed ten 5-ml water swallows and one each of 1-, 10-, and 20-ml volume swallows. Pressure profiles across the UES were analyzed using customized computational algorithms that measured 1) the relaxation interval (RI), 2) the median intrabolus pressure (mIBP) during the RI, and 3) the deglutitive sphincter resistance (DSR) defined as mIBP/RI. The automated analysis succeeded in confirming bolus volume modulation of both the RI and the mIBP with the mean RI ranging from 0.32 to 0.50 s and mIBP ranging from 5.93 to 13.80 mmHg for 1- and 20-ml swallows, respectively. DSR was relatively independent of bolus volume. Peak pharyngeal contraction during the return to the resting state postswallow was almost 300 mmHg, again independent of bolus volume. We performed a detailed analysis of deglutitive UES relaxation with a novel HRM system and customized software. The enhanced spatial resolution of HRM allows for the accurate, automated assessment of UES relaxation and intrabolus pressure characteristics, in both cases confirming the volume-dependent effects and absolute values of these parameters previously demonstrated by detailed analysis of concurrent manometry/fluoroscopy data. Normative values were established to aid in future clinical and investigative studies.     

Cardiovascular response to arousal from sleep under controlled conditions of central and peripheral chemoreceptor stimulation in humans.

The cardiovascular response to an arousal occurring at the termination of an obstructive apnea is almost double that to a spontaneous arousal. We investigated the hypothesis that central plus peripheral chemoreceptor stimulation, induced by hypercapnic hypoxia (HH), augments the cardiovascular response to arousal from sleep. Auditory-induced arousals during normoxia and HH (>10-s duration) were analyzed in 13 healthy men [age 24 +/- 1 (SE) yr]. Subjects breathed on a respiratory circuit that held arterial blood gases constant, despite the increased ventilation associated with arousal. Arousals were associated with a significant increase in mean arterial blood pressure at 5 s (P < 0.001) and with a significant decrease in the R-R interval at 3 s (P < 0.001); however, the magnitude of the changes was not significantly different during normoxia compared with HH (mean arterial blood pressure: normoxia, 91 +/- 4 to 106 +/- 4 mmHg; HH, 91 +/- 4 to 109 +/- 5 mmHg; P = 0.32; R-R interval: normoxia, 1.12 +/- 0.04 to 0.90 +/- 0.05 s; HH, 1.09 +/- 0.05 to 0.82 +/- 0.03 [corrected] s; P = 0.78). Mean ventilation increased significantly at the second breath postarousal for both conditions (P < 0.001), but the increase was not significantly different between the two conditions (normoxia, 5.35 +/- 0.40 to 9.57 +/- 1.69 l/min; HH, 8.57 +/- 0.63 to 11.98 +/- 0.70 l/min; P = 0.71). We conclude that combined central and peripheral chemoreceptor stimulation with the use of HH does not interact with the autonomic outflow associated with arousal from sleep to augment the cardiovascular response.     

Cerebral blood flow responses to changes in oxygen and carbon dioxide in humans

This study characterized cerebral blood flow (CBF) responses in the middle cerebral artery to PCO2 ranging from 30 to 60 mmHg (1 mmHg = 133.322 Pa) during hypoxia (50 mmHg) and hyperoxia (200 mmHg). Eight subjects (25 +/- 3 years) underwent modified Read rebreathing tests in a background of constant hypoxia or hyperoxia. Mean cerebral blood velocity was measured using a transcranial Doppler ultrasound. Ventilation (VE), end-tidal PCO2 (PETCO2), and mean arterial blood pressure (MAP) data were also collected. CBF increased with rising PETCO2 at two rates, 1.63 +/- 0.21 and 2.75 +/- 0.27 cm x s(-1) x mmHg(-1) (p < 0.05) during hypoxic and 1.69 +/- 0.17 and 2.80 +/- 0.14 cm x s(-1) x mmHg(-1) (p < 0.05) during hyperoxic rebreathing. VE also increased at two rates (5.08 +/- 0.67 and 10.89 +/- 2.55 L min(-1) m mHg(-1) and 3.31 +/- 0.50 and 7.86 +/- 1.43 L x min(-1) x mmHg(-1)) during hypoxic and hyperoxic rebreathing. MAP and PETCO2 increased linearly during both hypoxic and hyperoxic rebreathing. The breakpoint separating the two-component rise in CBF (42.92 +/- 1.29 and 49.00 +/- 1.56 mmHg CO2 during hypoxic and hyperoxic rebreathing) was likely not due to PCO2 or perfusion pressure, since PETCO2 and MAP increased linearly, but it may be related to VE, since both CBF and VE exhibited similar responses, suggesting that the two responses may be regulated by a common neural linkage.     

Complete lower esophageal sphincter relaxation observed in some achalasia patients is functionally inadequate

Generally accepted manometric criteria for the diagnosis of achalasia are absent peristalsis and incomplete lower esophageal sphincter (LES) relaxation. However, in some patients with otherwise typical features of achalasia, esophageal manometry shows complete LES relaxation during swallowing. To establish whether such apparently complete LES relaxations are functionally adequate, we quantified changes in resistance to flow at the esophagogastric junction (EGJ) during wet swallowing. We studied seven achalasia patients with manometrically complete (>80%) LES relaxation, eight achalasia patients with incomplete (<40%) LES relaxation, and eight healthy volunteers. Complete LES relaxation on standard manometry (open-tip catheters) was confirmed in five of the seven achalasia patients by a Dentsleeve. Changes in EGJ resistance to flow were quantified using a pneumatic resistometer. Manometrically, the relaxation time span was significantly longer in patients with complete LES relaxation than in those with incomplete relaxation (7. 3 +/- 0.5 vs. 4.4 +/- 0.7 s; P < 0.05). The fall in EGJ resistance from basal values during swallowing was markedly reduced in both achalasia groups (21 +/- 8% in those with manometrically complete relaxation and 4 +/- 2% in those with incomplete relaxation) by comparison with healthy individuals, in whom resistance fell by 90 +/- 3% (P < 0.05 vs. both achalasia groups). The duration of EGJ resistance drop was also much shorter in achalasia with (0.7 +/- 0.2 s) and without (0.2 +/- 0.1 s) complete LES relaxation compared with healthy control values (6.6 +/- 1.2 s). Our results reveal that the apparently complete LES relaxation observed manometrically in some patients with achalasia is functionally inadequate since it is not associated with the normal profound fall in EGJ resistance to flow.     

Occlusion of the upper airway does not augment the cardiovascular response to arousal from sleep in humans.

The cardiovascular response to an arousal from sleep at the termination of an obstructive apnea is more than double that to a spontaneous arousal. We investigated the hypothesis that stimulation of respiratory mechanoreceptors, by inspiring against an occluded airway during an arousal from sleep, augments the accompanying cardiovascular response. Arousals (>10 s) from stage 2 sleep were induced by a 1-s auditory tone (85 dB) during a concomitant 1-s inspiratory occlusion (O) and without an occlusion [i.e., control arousal (C)] in 15 healthy men (mean +/- SE: age, 25 +/- 1 yr). Arousals were associated with a significant increase in mean arterial blood pressure (MAP) at 4 s (P < 0.001) and a significant decrease in R-R interval at 3 s (P < 0.001). However, the magnitude of the cardiovascular response was not different during C compared with O (MAP: C, 86 +/- 3 to 104 +/- 3 mmHg; O, 86 +/- 3 to 105 +/- 3 mmHg; P = 0.99. R-R interval: C, 1.12 +/- 0.03 to 0.89 +/- 0.04 s; O, 1.11 +/- 0.02 to 0.87 +/- 0.02 s, P = 0.99). Ventilation significantly increased during arousals under both conditions at the second breath (P < 0.001); this increase was not different between the two conditions (C: 4.40 +/- 0.29 to 6.76 +/- 0.61 l/min, O: 4.35 +/- 0.34 to 7.65 +/- 0.73 l/min; P = 0.31). We conclude that stimulation of the respiratory mechanoreceptors by transient upper airway occlusion is unlikely to interact with the arousal-related autonomic outflow to augment the cardiovascular response in healthy young men.     

Influence of central venous pressure change on plasma vasopressin in humans

After overnight food and fluid restriction, nine healthy males were examined before, during, and after lower body positive pressure (LBPP) of 11 +/- 1 mmHg (mean +/- SE) for 30 min and before, during, and after graded lower body negative pressure (LBNP) of -10 +/- 1, -20 +/- 2, and -30 +/- 2 mmHg for 20 min each. LBPP and LBNP were performed with the subject in the supine position in a plastic box encasing the subject from the xiphoid process and down, thus including the splanchnic area. Central venous pressure (CVP) during supine rest was 7.5 +/- 0.5 mmHg, increasing to 13.4 +/- 0.8 mmHg (P less than 0.001) during LBPP and decreasing significantly at each step of LBNP to 2.0 +/- 0.5 mmHg (P less than 0.001) at 15 min of -30 +/- 2 mmHg LBNP. Plasma arginine vasopressin (AVP) did not change significantly in face of this large variation in CVP of 11.4 mmHg. Mean arterial pressure increased significantly during LBPP from 100 +/- 2 to 117 +/- 3 Torr (P less than 0.001) and only at one point during LBNP of -30 +/- 2 mmHg from 102 +/- 1 to 115 +/- 5 mmHg (P less than 0.05). Heart rate did not change during LBPP but increased slightly from 51 +/- 3 to 55 +/- 3 beats/min (P less than 0.05) only at 7 min of LBNP of -30 +/- 2 mmHg. Plasma osmolality, sodium, and potassium did not change during the experiment. Hemoglobin concentration increased during LBPP and LBNP, whereas hematocrit only increased during LBNP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypoxemia alone does not explain blood pressure elevations after obstructive apneas

In patients with obstructive sleep apnea (OSA), substantial elevations of systemic blood pressure (BP) and depressions of oxyhemoglobin saturation (SaO2) accompany apnea termination. The causes of the BP elevations, which contribute significantly to nocturnal hypertension in OSA, have not been defined precisely. To assess the relative contribution of arterial hypoxemia, we observed mean arterial pressure (MAP) changes following obstructive apneas in 11 OSA patients during non-rapid-eye-movement (NREM) sleep and then under three experimental conditions: 1) apnea with O2 supplementation; 2) hypoxemia (SaO2 80%) without apnea; and 3) arousal from sleep with neither hypoxemia nor apnea. We found that apneas recorded during O2 supplementation (SaO2 nadir 93.6% +/- 2.4; mean +/- SD) in six subjects were associated with equivalent postapneic MAP elevations compared with unsupplemented apneas (SaO2 nadir 79-82%): 18.8 +/- 7.1 vs. 21.3 +/- 9.2 mmHg (mean change MAP +/- SD); in the absence of respiratory and sleep disruption in eight subjects, hypoxemia was not associated with the BP elevations observed following apneas: -5.4 +/- 19 vs. 19.1 +/- 7.8 mmHg (P less than 0.01); and in five subjects, auditory arousal alone was associated with MAP elevation similar to that observed following apneas: 24.0 +/- 8.1 vs. 22.0 +/- 6.9 mmHg. We conclude that in NREM sleep postapneic BP elevations are not primarily attributable to arterial hypoxemia. Other factors associated with apnea termination, including arousal from sleep, reinflation of the lungs, and changes of intrathoracic pressure, may be responsible for these elevations.     

Regulation of atrial natriuretic peptide release in normal humans.

Atrial volume, pressure, and heart rate are considered the most important modulators of atrial natriuretic peptide (ANP) release, although their relative role is unknown. Continuous positive-pressure breathing in normal humans may cause atrial pressure and atrial volume to go in opposite directions (increase and decrease, respectively). We utilized this maneuver to differentially manipulate atrial volume and atrial pressure and evaluate the effect on ANP release. Effective filling pressure (atrial pressure minus pericardial pressure) was also monitored, because this variable has been proposed as another modulator of ANP secretion. We measured right atrial (RA) pressure, RA area, esophageal pressure (reflection of pericardial pressure), and RA and peripheral venous ANP in seven healthy adult males at rest and during continuous positive-pressure breathing (19 mmHg for 15 min). Continuous positive-pressure breathing decreased RA area (mean +/- SE, *P less than 0.05) 13.6 +/- 1.1 to 10.5 +/- 0.8* cm2, increased RA pressure 4 +/- 1 to 16 +/- 1* mmHg, increased esophageal pressure 2 +/- 1 to 12 +/- 1* mmHg, and increased effective filling pressure 2 +/- 0 to 4 +/- 1* mmHg. RA ANP increased from 67 +/- 17 to 91 +/- 18* pmol/l and peripheral venous ANP from 43 +/- 4 to 58 +/- 6* pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction of the autonomic nervous system with intrinsic cardiac rate regulation in the guinea-pig, Cavia porcellus.

In the denervated mammalian heart a change in right atrial pressure will still alter heart rate (intrinsic rate response, IRR). We have examined the IRR in isolated right atria of the guinea-pig maintained in oxygenated Krebs-Henseleit solution at 37 degrees C, to compare with and extend studies in other species, and to determine whether the guinea-pig is a suitable model for electrophysiological studies of the IRR. Baseline diastolic transmural pressure was set at 2 mmHg. A 6-mmHg increase in right atrial pressure (RAP) caused an increase in atrial rate that reached a steady value of 15 min(-1) after 1-2 min. This response was enhanced by carbamylcholine and attenuated by isoprenaline. The influence of RAP on the rate response to vagal stimulation was examined. With RAP set at 8 mmHg, the reduction in atrial rate following vagal stimulation was 72+/-5% of that at 2 mmHg (n=6, mean+/-S.E., P<0.005). Continuous vagal stimulation produced a sustained bradycardia, and the effect of this bradycardia on the IRR was examined. When atrial rate was reduced 6% by vagal stimulation, the IRR was augmented to 202+/-21% of the control (n=6, P<0.005). This augmentation was larger (P<0.05) than that seen when atrial rate was reduced 8% by carbamylcholine (130+/-8% of control; n=7, P<0.05). Overall, the IRR in the guinea-pig is similar to that in the rabbit, and shows similar interactions with the autonomic nervous system.     

Pressure morphology of the relaxed lower esophageal sphincter: the formation and collapse of the phrenic ampulla

This study aimed to apply novel high-resolution manometry with eight-sector radial pressure resolution (3D-HRM technology) to resolve the deglutitive pressure morphology at the esophagogastric junction (EGJ) before, during, and after bolus transit. A hybrid HRM assembly, including a 9-cm-long 3D-HRM array, was used to record EGJ pressure morphology in 15 normal subjects. Concurrent videofluoroscopy was used to relate bolus movement to pressure morphology and EGJ anatomy, aided by an endoclip marking the squamocolumnar junction (SCJ). The contractile deceleration point (CDP) marked the time at which luminal clearance slowed to 1.1 cm/s and the location (4 cm proximal to the elevated SCJ) at which peristalsis terminated. The phrenic ampulla spanned from the CDP to the SCJ. The subsequent radial and axial collapse of the ampulla coincided with the reconstitution of the effaced and elongated lower esophageal sphincter (LES). Following ampullary emptying, the stretched LES (maximum length 4.0 cm) progressively collapsed to its baseline length of 1.9 cm (P < 0.001). The phrenic ampulla is a transient structure comprised of the stretched, effaced, and axially displaced LES that serves as a "yield zone" to facilitate bolus transfer to the stomach. During ampullary emptying, the LES circular muscle contracts, and longitudinal muscle shortens while that of the adjacent esophagus reelongates. The likely LES elongation with the formation of the ampulla and shortening to its native length after ampullary emptying suggest that reduction in the resting tone of the longitudinal muscle within the LES segment is a previously unrecognized component of LES relaxation.     

Exercise training attenuates the myocardial dysfunction induced by endotoxin

The purpose of this study was to determine whether exercise training protected against endotoxin-induced myocardial dysfunction. After a 12-wk treadmill training period, carotid catheters were implanted 24 h before saline or endotoxin administration into four groups of animals: trained saline-injected (TS), trained endotoxin-injected (TE), sedentary saline-injected (SS), and sedentary endotoxin-injected (SE). Heart rate and mean arterial pressure were monitored 4 h after in vivo endotoxin or saline injection. Mean arterial pressure decreased an average of 32 +/- 3 mmHg 1 h after endotoxin administration but was normal (109 +/- 6 mmHg) 2 h later. Plasma catecholamines, in vitro myocardial performance, and isolated myocyte adenosine 3',5'-cyclic monophosphate (cAMP) production in response to isoproterenol were assessed 4 h after endotoxin injection. Plasma catecholamine levels were 5- to 15-fold higher in SE compared with the other groups. These data suggest that myocardial protection may be related to the lowered catecholamine levels elicited in TE compared with SE in response to endotoxin administration. The product of cardiac output and peak systolic pressure, an index of cardiac work, was 24-32% greater in TS compared with SS. Cardiac work was decreased 32% in TE compared with a 45% decrease in SE. cAMP was reduced in myocytes from SE in response to isoproterenol (-28%) and to forskolin (-44%) but not in myocytes from TE, compared with TS and SS. The difference in cAMP accumulation suggests that training maintains the integrity of the beta-adrenergic receptor adenylate cyclase system, which can be depressed by in vivo endotoxin administration.     

Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men

Large elastic artery compliance is reduced and arterial blood pressure (BP) is increased in the central (cardiothoracic) circulation with aging. Reactive oxygen species may tonically modulate central arterial compliance and BP in humans, and oxidative stress may contribute to adverse changes with aging. If so, antioxidant administration may have beneficial effects. Young (Y; 26 +/- 1 yr, mean +/- SE) and older (O; 63 +/- 2 yr, mean +/- SE) healthy men were studied at baseline and during acute (intravenous infusion; Y: n = 13, O: n = 12) and chronic (500 mg/day for 30 days; Y: n = 10, O: n = 10) administration of ascorbic acid (vitamin C). At baseline, peripheral (brachial artery) BP did not differ in the two groups, but carotid artery compliance was 43% lower (1.2 +/- 0.1 vs. 2.1 +/- 0.1 mm(2)/mmHg x 10(-1), P < 0.01) and central (carotid) BP (systolic: 116 +/- 5 vs. 101 +/- 3 mmHg, P < 0.05, and pulse pressure: 43 +/- 4 vs. 36 +/- 3 mmHg, P = 0.16), carotid augmentation index (AIx; 27.8 +/- 7.8 vs. -20.0 +/- 6.6%, P < 0.001), and aortic pulse wave velocity (PWV; 950 +/- 88 vs. 640 +/- 38 cm/s, P < 0.01) were higher in the older men. Plasma ascorbic acid concentrations did not differ at baseline (Y: 71 +/- 5 vs. O: 61 +/- 7 micromol/l, P = 0.23), increased (P < 0.001) to supraphysiological levels during infusion (Y: 1240 +/- 57 and O: 1,056 +/- 83 micromol/l), and were slightly elevated (P < 0.001 vs. baseline) with supplementation (Y: 96 +/- 5 micromol/l vs. O: 85 +/- 6). Neither ascorbic acid infusion nor supplementation affected peripheral BP, heart rate, carotid artery compliance, central BP, carotid AIx, or aortic PWV (all P > 0.26). These results indicate that the adverse changes in large elastic artery compliance and central BP with aging in healthy men are not 1). mediated by ascorbic acid-sensitive oxidative stress (infusion experiments) and 2). affected by short-term, moderate daily ascorbic acid (vitamin C) supplementation.     

High altitude and blood pressure in children

We aimed to evaluate the blood pressure of children who had similar demographic characteristics but lived at different altitudes. Blood pressure of the children attending primary schools in Izmir (sea level: n = 425) and Van (altitude: 1725 m, n = 291) were measured by mercurial sphygmomanometer for this study. They were similar with respect to age, sex, weight, height, and BMI. Mean age of the children was 10.51 +/- 0.87 years (range: 9 to 12 years), and 358 (50 percent) of them were female. Mean systolic blood pressure was significantly higher in the children living in Van than in the children living in Izmir (104.72 +/- 11.2 vs. 97.96 +/- 25.5 mmHg, respectively, p < .001). Similarly mean diastolic blood pressure was significantly higher in the children living in Van than in the children living in Izmir (63.98 +/- 9.3 vs. 59.91 +/- 10.0 mmHg, respectively, p < .001). When blood pressure was evaluated with regard to height percentile, the number of children with a blood pressure over 90 percentile were 19 (4.5 percent) and 48 (16.5 percent) for systolic blood pressure, and 25 (5.9 percent) and 37 (12.7 percent) for diastolic blood pressure among the children living in Izmir and Van, respectively (p < .001). Systolic and diastolic blood pressures were found to increase in parallel to the increase in body mass index in children living in Van (r = 0.358, p < .001 and r = 0.235, p < .001, respectively). However, blood pressures were not correlated to body mass index in children living in Izmir. A difference of 1700 m in altitude was associated with higher systolic and diastolic blood pressure levels in children with similar demographic characteristics, and at this altitude, body mass index and blood pressure showed a positive correlation.     

Esophageal tone in patients with total aperistalsis: gastroesophageal reflux disease versus achalasia

We have evaluated esophageal tone in two different conditions that, in some cases, similarly impair phasic esophageal motility. Studies were performed in 14 healthy volunteers, 10 patients with total esophageal aperistalsis secondary to gastroesophageal reflux disease (GERD), and 25 untreated achalasia patients. We quantified esophageal compliance and relaxation induced by a nitric oxide donor using a barostat. Intraesophageal volume at a minimal distending pressure (2 mmHg) was not significantly different among all three groups (4.1 +/- 0.7, 3.8 +/- 0.7, and 4.2 +/- 1.2 ml for healthy, GERD, and achalasia groups, respectively). Esophageal compliance was significantly increased (P < 0.05 vs. healthy group) in the two groups of patients with aperistalsis (1.9 +/- 0.2, 3.0 +/- 0.2, and 3.1 +/- 0.3 ml/mmHg for healthy, GERD, and achalasia groups, respectively). Esophageal relaxation was decreased in GERD patients (Delta diameter: 0.4 +/- 0.1 cm) and increased in achalasia patients (Delta diameter: 1.3 +/- 0.4 cm) relative to healthy subjects (Delta diameter: 0.9 +/- 0.2 cm) (P < 0.05 for GERD vs. achalasia and healthy groups). Our results indicate that diseases that similarly impair phasic esophageal motility may affect esophageal tone differently.     

Effects of phentolamine on hepatic PO2 in endotoxemia

The effect of phentolamine, an alpha-adrenergic blocker, on hepatic oxygen supply, plasma glucose, and lactate, and survival in fasted male rats administered Echerichia coli endotoxin (25 mg/kg, ip) has been studied. Survival at 24 h was 8% in untreated endotoxic rats, 83% in rats receiving phentolamine (5 mg/kg, ip) and endotoxin, and 100% in phentolamine controls. Measurements during the initial 8 h postendotoxin recorded transiently lower systemic arterial pressure in the phentolamine-endotoxic rats. Arterial PO2 and increases of pH and heart rate were similar in both endotoxic groups. Lactacidemia, present by 4 h in untreated endotoxic rats, did not develop in the phentolamine group and plasma glucose was significantly higher at 8 h (98 +/- 2.5 vs. 77 +/- 5.6 mg%, mean +/- SE). Mean hepatic PO2 at 6 h in phentolamine-endotoxic rats was 9.6 mmHg with 28% of the values below 5 mmHg. By contrast, the mean in untreated endotoxic rats was 1.9 mmHg with 88% of values below 5 mmHg. Phentolamine controls were stable over 8 h; mean hepatic PO2 was 17.7 mmHg. The differences in plasma glucose and lactate suggest protection of hepatic metabolism in phentolamine-treated endotoxic rats by prevention of excessive hepatic hypoxia.