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Postural orthostatic tachycardia syndrome (POTS) is a disorder epitomized by the story of the blind men and the elephant. Patients may see primary care internists or pediatricians due to fatigue, be referred to neurologists for “spells”, to cardiologists for evaluation of pre-syncope or chest pain, to gastroenterologists for nausea or dyspepsia, and even pulmonologists for dyspnea. Adoption of a more systematic approach to their evaluation and better characterization of patients has led to greater understanding of comorbidities, hypotheses prompting mechanistic investigations, and pharmacologic trials. Recent work has implicated disordered sympathetic nervous system activation in response to central (thoracic) hypovolemia. It is this pathway that leads one zero in on a putative focal point from which many of the clinical manifestations can be explained – specifically the carotid body. Despite heterogeneity in etiopathogenesis of a POTS phenotype, we propose that aberrant activation and response of the carotid body represents one potential common pathway in evolution. To understand this postulate, one must jettison isolationist or reductionist ideas of chemoreceptor and baroreceptor functions of the carotid body or sinus, respectively, and consider their interaction and interdependence both locally and centrally where some of its efferents merge. Doing so enables one to connect the dots and appreciate origins of diverse manifestations of POTS, including dyspnea for which the concept of neuro-mechanical uncoupling is wanting, thereby expanding our construct of this symptom. This perspective expounds our premise that POTS has a prominent respiratory component.

ObjectiveSyncope is sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). We previously demonstrated impaired post-synaptic adrenergic responsiveness in young VVS patients was reversed by blocking nitric oxide synthase (NOS). We hypothesised that nitric oxide may account for reduced orthostatic tolerance in young recurrent VVS patients.MethodsWe recorded haemodynamics in supine VVS and healthy volunteers (aged 15–27 years), challenged with graded lower body negative pressure (LBNP) (−15, –30, −45 mm Hg each for 5 min, then −60 mm Hg for a maximum of 50 min) with and without NOS inhibitor NG-monomethyl-L-arginine acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and pressor control for L-NMMA.ResultsControls endured 25.9±4.0 min of LBNP during Saline+PE compared with 11.6±1.4 min for fainters (p<0.001). After L-NMMA, control subjects endured 24.8±3.2 min compared with 22.6±1.6 min for fainters. Mean arterial pressure decreased more in VVS patients during LBNP with Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased similarly in controls and VVS patients and was unaffected by L-NMMA. Total peripheral resistance increased for controls but decreased for VVS during Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular resistance increased during LBNP in controls, but decreased in VVS patients following Saline+PE which L-NMMA restored.ConclusionsWe conclude that arterial vasoconstriction is impaired in young VVS patients, which is corrected by NOS inhibition. The data suggest that both pre- and post-synaptic arterial vasoconstriction may be affected by nitric oxide.

POTS (postural tachycardia syndrome) is associated with low blood volume and reduced renin and aldosterone; however, the role of Ang (angiotensin) II has not been investigated. Previous studies have suggested that a subset of POTS patients with increased vasoconstriction related to decreased bioavailable NO (nitric oxide) have decreased blood volume. Ang II reduces bioavailable NO and is integral to the renin–Ang system. Thus, in the present study, we investigated the relationship between blood volume, Ang II, renin, aldosterone and peripheral blood flow in POTS patients. POTS was diagnosed by 70° upright tilt, and supine calf blood flow, measured by venous occlusion plethysmography, was used to subgroup POTS patients. A total of 23 POTS patients were partitioned; ten with low blood flow, eight with normal flow and five with high flow. There were ten healthy volunteers. Blood volume was measured by dye dilution. All biochemical measurements were performed whilst supine. Blood volume was decreased in low-flow POTS (2.14±0.12 litres/m2) compared with controls (2.76±0.20 litres/m2), but not in the other subgroups. PRA (plasma renin activity) was decreased in low-flow POTS compared with controls (0.49±0.12 compared with 0.90±0.18 ng of Ang I·ml−1·h−1 respectively), whereas plasma Ang II was increased (89±20 compared with 32±4 ng/l), but not in the other subgroups. PRA correlated with aldosterone (r=+0.71) in all subjects. PRA correlated negatively with blood volume (r=−0.72) in normal- and high-flow POTS, but positively (r=+0.65) in low-flow POTS. PRA correlated positively with Ang II (r=+0.76) in normal- and high-flow POTS, but negatively (r=−0.83) in low-flow POTS. Blood volume was negatively correlated with Ang II (r=−0.66) in normal- and high-flow POTS and in five low-flow POTS patients. The remaining five low-flow POTS patients had reduced blood volume and increased Ang II which was not correlated with blood volume. The data suggest that plasma Ang II is increased in low-flow POTS patients with hypovolaemia, which may contribute to local blood flow dysregulation and reduced NO bioavailability.

Simple faint (neurocardiogenic syncope) and postural tachycardia syndrome (POTS) characterize acute and chronic orthostatic intolerance respectively. We explored the hypothesis that vascular function is similar in the two conditions. We studied 29 patients with POTS and compared them with 20 patients with neurocardiogenic syncope who were otherwise well, and with 15 healthy control subjects. We measured continuous heart rate, respiration and blood pressure, and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow, peripheral arterial resistance, peripheral venous resistance and venous pressure (Pv). Upright tilt was performed to 70° for 10min, during which calf blood flow and volume were measured. Calf Pv was increased (to 27.2±2.0mmHg) in a subgroup of POTS patients, who also had increased arterial resistance (57±6mmHg·ml-1·min-1·100ml-1 tissue), increased venous resistance (2.4±0.3mmHg·ml-1·min-1·100ml-1 tissue), and decreased peripheral flow (1.0±0.2ml·min-1·100ml-1 tissue) in the calf; other POTS patients with a normal Pv had decreased arterial resistance (18±2mmHg·ml-1·min-1·100ml-1 tissue) and increased blood flow (3.8±0.3ml·min-1·100ml-1 tissue). Syncope patients were not different from controls (Pv = 11.4±0.5mmHg; calf flow = 3.1±0.2ml·min-1·100ml-1 tissue; arterial resistance = 27±2mmHg·ml-1·min-1·100ml-1 tissue; venous resistance = 1.2±0.3mmHg·ml-1·min-1·100ml-1 tissue). When upright, syncope patients and control subjects had similar increases in heart rate and calf volume, stable blood pressure, and decreases in blood flow. POTS patients had markedly increased heart rate and calf blood flow, unstable blood pressure, and pooling in the lower extremities, regardless of subgroup. We conclude that peripheral vascular physiology in patients with POTS is abnormal, in contrast with normal peripheral vascular physiology in neurocardiogenic syncope.

Orthostasis is characterized by translocation of blood from the upper body and thorax into dependent venous structures. Although active splanchnic venoconstriction is known to occur, active limb venoconstriction remains controversial. Based on prior work, we initially hypothesized that active venoconstriction does occur in the extremities during orthostasis in response to baroreflex activation. We investigated this hypothesis in the arms and legs of 11 healthy volunteers, aged 13–19 yr, using venous occlusion strain gauge plethysmography to obtain the forearm and calf blood flows and to compute the capacitance vessel volume-pressure compliance relation. Subjects were studied supine and at −10, +20, and +35° to load the baroreflexes. With +20° of tilt, blood flow decreased and limb arterial resistance increased significantly (P< 0.05) compared with supine. With +35° of tilt, blood flow decreased, limb arterial resistance increased, and heart rate increased, indicating parasympathetic withdrawal and sympathetic activation with arterial vasoconstriction. The volume-pressure relation was unchanged by orthostatic maneuvers. The results suggest that active venoconstriction in the limbs is not important to mild orthostatic response.

Instantaneous orthostatic hypotension INOH has been reported in children and adolescents as a new entity of orthostatic intolerance in children who underwent rapid standing as an orthostatic stress test. Children with INOH were discovered among patients presenting with symptoms of chronic orthostatic intolerance, which is often related to orthostatic tachycardia. We used headup tilt table testing at 70° to investigate children presenting with symptoms of chronic orthostatic intolerance. We compared 24 patients aged 1217 y, with chronic orthostatic intolerance and symptoms for =3 mo, with 13 healthy normal control patients. We recorded continuous heart rate, blood pressure, and respiratory rate and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow while supine and calf blood flow during headup tilt. Patients with chronic orthostatic intolerance fulfilled criteria for the postural orthostatic tachycardia syndrome. Postural orthostatic tachycardia syndrome patients were divided into two groups by the occurrence of INOH. Supine forearm and calf arterial resistance was decreased in patients with INOH n8 compared with postural orthostatic tachycardia syndrome patients without INOH n16 and compared with control n13. Resting calf venous pressure was elevated, suggesting excess venous filling because of vasodilation. During early headup tilt, calf blood flow increased markedly in INOH, less in NoINOH, postural orthostatic tachycardia syndrome patients and least in control patients. Flow was temporally related to calf swelling and negatively correlated to hypotension. The data suggest that INOH occurs in patients with chronic orthostatic intolerance and orthostatic tachycardia and is related to rapid caudal blood flow when upright because of a vasoconstrictor defect.

Instantaneous orthostatic hypotension (INOH) has been reported in children and adolescents as a new entity of orthostatic intolerance in children who underwent rapid standing as an orthostatic stress test. Children with INOH were discovered among patients presenting with symptoms of chronic orthostatic intolerance, which is often related to orthostatic tachycardia. We used head-up tilt table testing at 70° to investigate children presenting with symptoms of chronic orthostatic intolerance. We compared 24 patients aged 12–17 y, with chronic orthostatic intolerance and symptoms for =3 mo, with 13 healthy normal control patients. We recorded continuous heart rate, blood pressure, and respiratory rate and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow while supine and calf blood flow during head-up tilt. Patients with chronic orthostatic intolerance fulfilled criteria for the postural orthostatic tachycardia syndrome. Postural orthostatic tachycardia syndrome patients were divided into two groups by the occurrence of INOH. Supine forearm and calf arterial resistance was decreased in patients with INOH (n = 8) compared with postural orthostatic tachycardia syndrome patients without INOH (n = 16) and compared with control (n = 13). Resting calf venous pressure was elevated, suggesting excess venous filling because of vasodilation. During early head-up tilt, calf blood flow increased markedly in INOH, less in No-INOH, postural orthostatic tachycardia syndrome patients and least in control patients. Flow was temporally related to calf swelling and negatively correlated to hypotension. The data suggest that INOH occurs in patients with chronic orthostatic intolerance and orthostatic tachycardia and is related to rapid caudal blood flow when upright because of a vasoconstrictor defect.

Instantaneous orthostatic hypotension (INOH) has been reported in children and adolescents as a new entity of orthostatic intolerance in children who underwent rapid standing as an orthostatic stress test. Children with INOH were discovered among patients presenting with symptoms of chronic orthostatic intolerance, which is often related to orthostatic tachycardia. We used head-up tilt table testing at 70° to investigate children presenting with symptoms of chronic orthostatic intolerance. We compared 24 patients aged 12–17 y, with chronic orthostatic intolerance and symptoms for ≥3 mo, with 13 healthy normal control patients. We recorded continuous heart rate, blood pressure, and respiratory rate and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow while supine and calf blood flow during head-up tilt. Patients with chronic orthostatic intolerance fulfilled criteria for the postural orthostatic tachycardia syndrome. Postural orthostatic tachycardia syndrome patients were divided into two groups by the occurrence of INOH. Supine forearm and calf arterial resistance was decreased in patients with INOH (n8) compared with postural orthostatic tachycardia syndrome patients without INOH (n16) and compared with control (n13). Resting calf venous pressure was elevated, suggesting excess venous filling because of vasodilation. During early head-up tilt, calf blood flow increased markedly in INOH, less in No-INOH, postural orthostatic tachycardia syndrome patients and least in control patients. Flow was temporally related to calf swelling and negatively correlated to hypotension. The data suggest that INOH occurs in patients with chronic orthostatic intolerance and orthostatic tachycardia and is related to rapid caudal blood flow when upright because of a vasoconstrictor defect.

Dependent pooling occurs in postural orthostatic tachycardia syndrome (POTS) related to defective vasoconstriction. Increased venous pressure (Pv) >20 mmHg occurs in some patients (high Pv) but not others (normal Pv). We compared 22 patients, aged 12–18 yr, with 13 normal controls. Continuous blood pressure and strain-gauge plethysmography were used to measure supine forearm and calf blood flow, resistance, venous compliance, and microvascular filtration, and blood flow and swelling during 70° head-up tilt. Supine, high Pv had normal resistance in arms (26 ± 2 mmHg · ml−1· 100 ml · min) and legs (34 ± 3 mmHg · ml−1· 100 ml · min) but low leg blood flow (1.5 ± 0.4 ml · 100 ml−1· min−1). Supine leg Pv (30 ± 2 vs. 13 ± 1 mmHg in control) exceeded the threshold for edema (isovolumetric pressure = 19 ± 3 mmHg). Supine, normal Pv had high blood flow in arms (4.1 ± 0.2 vs. 3.5 ± 0.2 ml · 100 ml−1· min−1in control) and legs (3.8 ± 0.4 vs. 2.7 ± 0.3 ml · 100 ml−1· min−1in control) with low resistance. With tilt, calf blood flow increased steadily in POTS with high Pv and transiently increased in normal Pv. Calf volume increased in all POTS patients. Arm blood flow increased in normal Pv only with forearm maintained at heart level. These data suggest that there are (at least) two subgroups of POTS characterized by high Pv and low flow or normal Pv and high flow. These may correspond to abnormalities in local or baroreceptor-mediated vasoconstriction, respectively.

Chronic orthostatic intolerance is often related to the postural orthostatic tachycardia syndrome (POTS). POTS is characterized by upright tachycardia. Understanding of its pathophysiology remains incomplete, but edema and acrocyanosis of the lower extremities occur frequently. To determine how arterial and venous vascular properties account for these findings, we compared 13 patients aged 13–18 yr with 10 normal controls. Heart rate and blood pressure were continuously recorded, and strain-gauge plethysmography was used to measure forearm and calf blood flow, venous compliance, and microvascular filtration while the subject was supine and to measure calf blood flow and calf size change during head-up tilt. Resting venous pressure was higher in POTS compared with control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in these patients. The threshold for edema formation decreased in POTS patients compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow increased in POTS patients (from 3.4 ± 0.9 to 12.6 ± 2.3 ml · 100 ml−1· min−1) but did not increase in controls. Calf volume increased twice as much in POTS patients compared with controls over a shorter time of orthostasis. The data suggest that resting venous pressure is higher and the threshold for edema is lower in POTS patients compared with controls. Such findings make the POTS patients particularly vulnerable for edema fluid collection. This may signify a redistribution of blood to the lower extremities even while supine, accounting for tachycardia through vagal withdrawal.

The objective was to determine the nature of autonomic and vasomotor changes in adolescent patients with orthostatic tachycardia associated with the chronic fatigue syndrome (CFS) and the postural orthostatic tachycardia syndrome (POTS). Continuous electrocardiography and arterial tonometry was used to investigate the heart rate and blood pressure responses before and 3–5 min after head-up tilt in 22 adolescents with POTS and 14 adolescents with CFS, compared with control subjects comprising 10 healthy adolescents and 20 patients with simple faint. Heart rate and blood pressure variability, determined baroreceptor function using transfer function analysis, and measured cardiac vagal and adrenergic autonomic responses were calculated using timed breathing and the quantitative Valsalva maneuver. Two of 10 healthy controls and 14 of 20 simple faint patients experienced vasovagal syncope during head-up tilt. By design, all CFS and POTS patients experienced orthostatic tachycardia, often associated with hypotension. R-R interval and heart rate variability were decreased in CFS and POTS patients compared with control subjects and remained decreased with head-up tilt. Low-frequency (0.05–0.15 Hz) blood pressure variability reflecting vasomotion was increased in CFS and POTS patients compared with control subjects and increased further with head-up tilt. This was associated with depressed baroreflex transfer indicating baroreceptor attenuation through defective vagal efferent response. Only the sympathetic response remained. Heart rate variability declined progressively from normal healthy control subjects through syncope to POTS to CFS patients. Timed breathing and Valsalva maneuver were most often normal in CFS and POTS patients, although abnormalities in select individuals were found. Heart rate and blood pressure regulation in POTS and CFS patients are similar and indicate attenuated efferent vagal baroreflex associated with increased vasomotor tone. Loss of beat-to-beat heart rate control may contribute to a destabilized blood pressure resulting in orthostatic intolerance. The dysautonomia of orthostatic intolerance in POTS and in chronic fatigue are similar.

The objective was to determine the nature of autonomic and vasomotor changes in adolescent patients with orthostatic tachycardia associated with the chronic fatigue syndrome (CFS) and the postural orthostatic tachycardia syndrome (POTS). Continuous electrocardiography and arterial tonometry was used to investigate the heart rate and blood pressure responses before and 3–5 min after head-up tilt in 22 adolescents with POTS and 14 adolescents with CFS, compared with control subjects comprising 10 healthy adolescents and 20 patients with simple faint. Heart rate and blood pressure variability, determined baroreceptor function using transfer function analysis, and measured cardiac vagal and adrenergic autonomic responses were calculated using timed breathing and the quantitative Valsalva maneuver. Two of 10 healthy controls and 14 of 20 simple faint patients experienced vasovagal syncope during head-up tilt. By design, all CFS and POTS patients experienced orthostatic tachycardia, often associated with hypotension. R-R interval and heart rate variability were decreased in CFS and POTS patients compared with control subjects and remained decreased with head-up tilt. Low-frequency (0.05–0.15 Hz) blood pressure variability reflecting vasomotion was increased in CFS and POTS patients compared with control subjects and increased further with head-up tilt. This was associated with depressed baroreflex transfer indicating baroreceptor attenuation through defective vagal efferent response. Only the sympathetic response remained. Heart rate variability declined progressively from normal healthy control subjects through syncope to POTS to CFS patients. Timed breathing and Valsalva maneuver were most often normal in CFS and POTS patients, although abnormalities in select individuals were found. Heart rate and blood pressure regulation in POTS and CFS patients are similar and indicate attenuated efferent vagal baroreflex associated with increased vasomotor tone. Loss of beat-to-beat heart rate control may contribute to a destabilized blood pressure resulting in orthostatic intolerance. The dysautonomia of orthostatic intolerance in POTS and in chronic fatigue are similar.

Exercise enhances the dilation of the epicardial coronary arteries by vasodilator drugs and blood flow. Our goal was to determine whether coronary artery elastic properties were affected by brief exercise training.

To determine whether dilation of large coronary arteries normalizes shear during increased flow following brief occlusion, six dogs were instrumented to measure aortic and left ventricular pressures, left circumflex coronary artery external diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30 s. Data were obtained before and after blockade of EDRF synthesis with nitro-L-arginine. Internal coronary artery diameter and wall shear were calculated on a moment-to-moment basis and the area under the flow curve was measured. Peak flow and shear rate were unaffected by NLA or by the occlusion duration. Flow curve area increased with the duration of occlusion. Internal and external diameters increased significantly for 15 s occlusions before NLA (by 4 ± 1% in external diameter and by 11 ± 4% in internal diameter) and for 30 s occlusions before NLA (by 5 ± 1% in external diameter and by 14 ± 5% in internal diameter) but not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 μmol/kg/min were also used to dilate the coronary arteries. With each infusion, flow, shear and diameter were allowed to reach steady state. Steady state shear was reduced only slightly and did not approach the baseline state. We conclude that increased shear rate causes an increase in coronary artery diameter which is EDRF dependent. Increased coronary artery diameter during reactive hyperemia and adenosine infusions did not normalize wall shear.

The Fontan procedure results in right atrial distention and is complicated by fluid retention. Since systemic fluid balance may be hormonally mediated in part and related to right atrium size, we measured plasma atrial natriuretic factor and plasma arginine vasopressin levels in 19 patients undergoing the Fontan procedure and in 12 control patients undergoing other types of heart operations. Preoperative plasma atrial natriuretic factor levels were higher in patients undergoing the Fontan procedure than in control patients (95 ± 16 pg/ml preoperatively versus 50 ± 8 pg/ml; p < 0.05) and increased in patients undergoing the Fontan procedure to 330 ± 48 pg/ml by postoperative day 2 (p < 0.05) but not in control patients. Increased plasma atrial natriuretic factor levels could enhance capillary transudation, but elevated plasma atrial natriuretic factor levels should also enhance diuresis and prevent fluid retention. Vasopressin levels, however, were also increased in patients undergoing the Fontan procedure (from 9 ± 2 pg/ml preoperatively to 144 ± 37 pg/ml at end of operation) and were higher and remained elevated longer than in control patients undergoing heart operations (37 ± 7, 20 ± 4, 16 ± 6 pg/ml on postoperative days 1, 2, and 3 to 10 for the Fontan group compared with 15 ± 4, 4 ± 1, 4 ± 2 pg/ml for control patients). Vasopressin levels were highest in the Fontan group with the most severe fluid retention and effusions (for example, 51 ± 10 pg/ml versus 23 ± 4 pg/ml, on postoperative day 1). Increased vasopressin and atrial natriuretic factor could act synergistically to result in the development of effusions after the Fontan procedure when atrial natriuretic factor–induced capillary transudation is combined with vasopressin–induced antidiuresis.

Neurocardiogenic syncope may be caused by enhanced sympathetic activity evoking a vasodepressor-cardioinhibitory reflex. Heart rate variability (HRV) methods can be used to assess the modulation of sympathetic and parasympathetic activity. To determine whether HRV measurements are related to the outcome of head-up tilt testing (HUT), we studied 29 syncopal patients aged 7-19 y. After 30 min supine, patients were tilted to 80 ° for 30 min or until syncope occurred. Sequential beats free from ectopy were analyzed. Time domain indices included SD (SDNN), root mean square successive differences (RMSSD), percent exceeding 50 ms (pNN50). An autoregressive model was used to calculate power spectra. Low frequency power (LFP, 0.05-0.15 Hz), high frequency power (HFP, 0.15-0.40 Hz), and total power (TP, 0.01-0.40 Hz) were compared before and after tilt. Data were obtained supine before tilt(baseline), within 5 min after HUT (early), 5-10 min after HUT (mid), and 15 min after HUT or presyncope (late). Seventeen patients fainted (HUT+), and 12 patients did not (HUT-). Variability indices were different for HUT-and HUT+at baseline: SDNN was 123 ± 17versus 78 ± 6, RMSSD was 127 ± 23 versus 64± 6 ms, pNN50 was 51 ± 6 versus 31 ± 4, respectively. Spectral data demonstrated decreased HFP and TP in HUT+(834 ± 133 and 2855 ± 420 ms2) versus HUT-(3433 ± 840 and 7062 ± 1500). With tilt, SDNN, RMSSD, and pNN50 decreased proportionately in HUT-and HUT+. However, sympathovagal balance, measured by the ratio LFP/HFP and by normalized LFP, was markedly increased in HUT+(2.2 ± 0.7 and 0.43 ± 0.03) compared with HUT-(0.8 ± 0.2 and 0.31± 0.02) at baseline and differences increased with tilt. With syncope, sympathetic activity decreased, and parasympathetic activity increased. Decreased RR variability with decreased parasympathetic activity and increased indices of sympathovagal balance before HUT predict a positive tilt test in children referred for evaluation of neurocardiogenic syncope.

Arginine vasopressin levels in 17 neonates with cardiac disease were compared with control levels in 10 healthy newborn infants. Infants with congestive heart failure who were free of left ventricular outflow tract obstruction had a mean level of 80 ± 18 pg/ml, which was significantly greater than the mean control level (p < 0.001). Infants with congestive heart failure and left ventricular outflow tract obstruction had a mean vasopressin level of 3 ± 0.7 pg/ml, which was lower than the mean control level of 6 ± 0.7 pg/ml (p < 0.05).

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To assess RR variability during head up tilt (HUT) we studied 20 syncopal pts aged 7–18y with Holter monitor. After 30 min supine, pts were tilted to 80° for 30min or until syncope occurred. Sequential 256 and 512 beat epochs free from ectopy were analyzed. Mean and standard deviation, root mean square (RMSSD), fraction exceeding 50msec (pN50) and correlation coefficient (r) of successive differences were computed. An autoregressive power spectrum model was used. Low frequency power (LFP, 0.05–0.15Hz). high frequency power (HFP, 0.15–040Hz), and total power (TP, 0.01–0.40Hz) were compared. Epochs while supine, within 5 minutes after HUT, 5–10 min after HUT, and 15min after or during syncope were analyzed. 12 pts fainted (F) and B did not (N). RR interval was 910±6 for N and 870±4 msec for F (p=NS). Indices of RR variability were markedly different (p&lt;0.05) for F and N while supine: RMSSD was 128±22 for N vs 62±7msec for F, pN50 was 0.51±0.06 for N vs 0.33±0.04 for F, r was 0.50±0.06 for N vs 0.70±0.05 for F. LFP was 920±140 in N vs 1710±440 msec2in F (p=NS), while HFP and TP were 2990±840 and 7062±1500 in N vs 834±130 and 2855±420 msec2in F (p&lt;0.05). With HUT RR decreased similarly in F and N (25±3% and 26±3%) while RMSSD and pN50 decreased proportionately in N (by 59±5% and 63±10%) and in F (by 59±4% and 83±5%, p=NS). RMSSD and pN50 remained higher in N vs F after tilt. r increased for N (to 0.77±0.05) and F (to 0.88±0.02) but remained higher in F reflecting lower variability. LFP, HFP, and TP decreased proportionately for each group. Thus HFP and TP remained higher in N than F. Similar results were obtained after 5–10 minutes of HUT in Nand F and after 15 minutes in N. In F prior to syncope, RR increased to 1,045±50msec, RMSSD to 125±25 msec, PN50 to 0.41±0.05, and r fell to 0.51±0.04, while TP increased to 5200±1343 msec2, LFP increased to 1717±601 msec2, and HFP increased to 2730±1075 msec2. Relatively decreased RR variability supine prior to HUT predicts syncope and is primarily caused by decreased high frequency power.

In addition to its antidiuretic properties, arginine vasopressin (AVP) is a potent vasoactive homone. If unopposed by baroreceptor mediated reflexes, even low serun levels of AVP nay exert pressor effects. Since early life is associated with an enhanced ability to release AVP and with an increase in its cardiovascular effects, we evaluated whether congestive heart failure (CHF) is a stimulus for AVP release. AVP levels were measured by RIA using the modified Bentonite technique in 40 infants and children divided into 5 groups: Group I (n = 7) with CHF; Group II (n = 6) with cyanotic heart disease; Group III(n = 3) with persistent neonatal pulmonary hypertension; Group IV (n = 12) stressed infants with respiratory disease but no heart disease; and Group V (n = 12) healthy unstressed controls. Group IV had statistically higher AVP levels (13 pcg/ml ± 6) when compared to Group V normals (6 peg/ml ± 2)(p ≤ 0.05). Groups II & III were not significantly different from Group V (7 pcg/ml ± 5 and 6 peg/ml ± 2 respectively). CHF patients (Group I) had variable AVP levels with peak levels markedly elevated above other groups (102 peg/ml ± 135), (p<0.05) and further increased with worsening clinical status.Additional data suggest that hyperosrrotic angiographic contrast madia increase AVP levels by 2 to 10 times pre-dye levels in most instances (n = 12 of 15 patients, p < 0.02).We conclude that AVP levels are increased in children with CHF and that diagnostic interventions such as angiography may further elevate AVP. This may result in increased cardiac afterload further impairing already diminished cardiac function.

Study objective — The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo. Design — Acute graded haemorrhage, 30 ml·kg−1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch. Experimental material — Awake mongrel dogs (n=6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n=4) were instrumented for measurement of left and right atrial appendage pressures and diameters. Measurements and main results — During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg·ml−1 (p<0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p<0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg·ml−1. Conclusions — Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.