scholarly journals Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options

2016 ◽  
Vol 310 (3) ◽  
pp. H416-H425 ◽  
Author(s):  
Ashley L. Wagoner ◽  
Hossam A. Shaltout ◽  
John E. Fortunato ◽  
Debra I. Diz

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10–18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI.

1978 ◽  
Vol 75 (1) ◽  
pp. 65-79 ◽  
Author(s):  
H. B. Lillywhite ◽  
R. S. Seymour

1. Blood pressure was measured in the dorsal aorta of restrained, unanaesthetized tiger snakes (Notechis scutatus) at different body temperatures during graded, passive tilt. Aortic blood pressure in horizontal snakes showed no significant change over a range of body temperatures between 18 and 33 degrees C (mean of measurements on 16 snakes = 42.2 +/− I.98 mmHg), while heart rate increased logarithmically (Q10 approximately 2.5). Blood pressure was stable during heating and cooling between body temperatures of 15 and 30 degrees C, but the pressure was 10--50% higher during heating than during cooling. 2. Head-up tilt usually caused a brief fall in pressure at heart level followed by partial or complete recovery and tachycardia. At the cessation of tilt, there was a characteristic overshoot of the blood pressure followed by readjustment to control (pretilt) levels. Head-down tilt typically increased pressure which then either stabilized or returned toward pretilt levels. Heart rate changes during head-down tilt were not consistent in direction or magnitude. Stabilized pressures at mid-body usually increased following head-up tilt and decreased following head-down tilt, indicating physiological adjustment to posture change. Blood pressure control was evident at body temperatures ranging from 10 to 38 degrees C, but was most effective at the higher and behaviourally preferred temperatures. 3. Propranolol lowered heart rate but did not influence pressure in horizontal snakes. During head-up tilt propranolol eliminated or reduced tachycardia and sometimes reduced the efficacy of pressure compensation for tilt. Phentolamine increased heart rate, lowered blood pressure, and eliminated pressure regulation during tilt. The results suggest that sympathetically mediated reflexes assist central blood pressure regulation in the tiger snake, with vasomotor adjustments having greater importance than changes in heart rate.


2014 ◽  
Vol 25 (5) ◽  
pp. 911-917 ◽  
Author(s):  
Yilmaz Yozgat ◽  
Cem Karadeniz ◽  
Rahmi Ozdemir ◽  
Onder Doksoz ◽  
Mehmet Kucuk ◽  
...  

AbstractObjective: To assess haemodynamic patterns in head-up tilt testing on 400 paediatric cases with unexplained syncope. Methods: Medical records of 520 children who underwent head-up tilt testing in the preceding year were retrospectively evaluated, and 400 children, 264 (66%) girls and 136 (34%) boys, aged 12.6±2.6 years (median 13; range 5–18), with unexplained syncope were enrolled in the study. Age, sex, baseline heart rate, baseline blood pressure, frequency of symptoms, and/or fainting attacks were recorded. The test protocol consisted of 25 minutes of supine resting followed by 20 minutes of 70° upright positioning. Subjects were divided into nine groups according to their differing haemodynamic patterns. Results: There were no statistically significant differences between the groups with regard to age, gender, baseline blood pressure, and frequency of syncope (p>0.05). The response was compatible with orthostatic intolerance in 28 cases (7.0%), postural orthostatic tachycardia syndrome in 24 cases (6.0%), asymptomatic postural orthostatic tachycardia syndrome in 26 cases (6.5%), orthostatic hypotension in seven cases (1.7%), vasovagal syncope in 38 cases (9.5%), and negative in 274 cases (69.2%). Vasovagal syncope response patterns were of type 3 in nine cases (2.2%), type 2A in 10 cases (2.5%), type 2B in two cases (0.5%), and type 1 (mixed) in 17 cases (4.25%). Conclusions: In the 400 paediatric cases with unexplained syncope, nine different haemodynamic response patterns to head-up tilt testing were discerned. Children with orthostatic intolerance syndromes are increasingly referred to hospitals because of difficulty in daily activities. Therefore, there is need for further clinical trials in these patient groups.


2014 ◽  
Vol 63 (6) ◽  
pp. 435-438 ◽  
Author(s):  
Kunihiko Tanaka ◽  
Shiori Tokumiya ◽  
Yumiko Ishihara ◽  
Yumiko Kohira ◽  
Tetsuro Katafuchi

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz J Baudenbacher ◽  
Susan S Eagle ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
...  

Introduction: Experimental models of hemorrhagic shock (HS) in rats are important to test new treatments that may improve outcomes in humans, and general anesthesia is required during these experiments. The volatile anesthetic Isoflurane is known for its beneficial effects in rat HS models. Focusing on cardiovascular compensatory mechanisms, we wanted to evaluate Isoflurane versus the injectable anesthetic Pentobarbital in our rat model of mild HS (class 2). We hypothesize that Isoflurane during development of HS improves hemodynamics compared to Pentobarbital. Methods: Twelve Sprague-Dawley rats were initially anesthetized with an intraperitoneal (IP) injection of Pentobarbital (45 mg/kg) and intubated (1 L/min, FiO 2 0.25); heart rate (HR) was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids, respectively. In one group (n=7), anesthesia was continued with repeated IP injections of Pentobarbital (dose mg/kg), the other group (n=5) received continuous Isoflurane (1%). After 30 min of stabilization and administration of Heparin (100 IU/kg), HS was induced by removal of 1 ml of blood over 1 min via the femoral vein, repeated every 3 min until a volume of 5 ml of blood was removed. Mean arterial blood pressure (MAP) and HR were recorded and analyzed in LabChart. Results: During baseline, rats showed no significant differences in HR and MAP between both groups. After 5 ml of hemorrhage, both groups showed significant changes compared to baseline, with significantly higher MAP and HR in rats given only Pentobarbital. Conclusions: In our rat model of HS, Isoflurane dampens the physiologic response to compensate for mild hemorrhage. The cardiovascular response of rats in the Isoflurane group was a decrease of HR and MAP to every ml of hemorrhage, while rats given only Pentobarbital were able to maintain their MAP by raising their HR until decompensation.


1992 ◽  
Vol 262 (6) ◽  
pp. E763-E778 ◽  
Author(s):  
I. A. Reid

The renin-angiotensin system plays an important role in the regulation of arterial blood pressure and in the development of some forms of clinical and experimental hypertension. It is an important blood pressure control system in its own right but also interacts extensively with other blood pressure control systems, including the sympathetic nervous system and the baroreceptor reflexes. Angiotensin (ANG) II exerts several actions on the sympathetic nervous system. These include a central action to increase sympathetic outflow, stimulatory effects on sympathetic ganglia and the adrenal medulla, and actions at sympathetic nerve endings that serve to facilitate sympathetic neurotransmission. ANG II also interacts with baroreceptor reflexes. For example, it acts centrally to modulate the baroreflex control of heart rate, and this accounts for its ability to increase blood pressure without causing a reflex bradycardia. The physiological significance of these actions of ANG II is not fully understood. Most evidence indicates that the actions of ANG to enhance sympathetic activity do not contribute significantly to the pressor response to exogenous ANG II. On the other hand, there is considerable evidence that the actions of endogenous ANG II on the sympathetic nervous system enhance the cardiovascular responses elicited by activation of the sympathetic nervous system.


2001 ◽  
Vol 281 (3) ◽  
pp. H1040-H1046 ◽  
Author(s):  
J. Kevin Shoemaker ◽  
Debbie D. O'Leary ◽  
Richard L. Hughson

Arterial hypocapnia has been associated with orthostatic intolerance. Therefore, we tested the hypothesis that hypocapnia may be detrimental to increases in muscle sympathetic nerve activity (MSNA) and total peripheral resistance (TPR) during head-up tilt (HUT). Ventilation was increased ∼1.5 times above baseline for each of three conditions, whereas end-tidal Pco 2 (Pet CO2 ) was clamped at normocapnic (Normo), hypercapnic (Hyper; +5 mmHg relative to Normo), and hypocapnic (Hypo; −5 mmHg relative to Normo) conditions. MSNA (microneurography), heart rate, blood pressure (BP, Finapres), and cardiac output (Q, Doppler) were measured continuously during supine rest and 45° HUT. The increase in heart rate when changing from supine to HUT ( P < 0.001) was not different across Pet CO2 conditions. MSNA burst frequency increased similarly with HUT in all conditions ( P < 0.05). However, total MSNA and the increase in total amplitude relative to baseline (%ΔMSNA) increased more when changing to HUT during Hypo compared with Hyper ( P < 0.05). Both BP and Q were higher during Hyper than both Normo and Hypo (main effect; P < 0.05). Therefore, the MSNA response to HUT varied inversely with levels of Pet CO2 . The combined data suggest that augmented cardiac output with hypercapnia sustained blood pressure during HUT leading to a diminished sympathetic response.


2020 ◽  
Vol 21 (21) ◽  
pp. 8349
Author(s):  
Ivona Kosovic ◽  
Natalija Filipovic ◽  
Benjamin Benzon ◽  
Ivana Bocina ◽  
Merica Glavina Durdov ◽  
...  

Our study analyzed the expression pattern of different connexins (Cxs) and renin positive cells in the juxtaglomerular apparatus (JGA) of developing, postnatal healthy human kidneys and in nephrotic syndrome of the Finnish type (CNF), by using double immunofluorescence, electron microscopy and statistical measuring. The JGA contained several cell types connected by Cxs, and consisting of macula densa, extraglomerular mesangium (EM) and juxtaglomerular cells (JC), which release renin involved in renin-angiotensin- aldosteron system (RAS) of arterial blood pressure control. During JGA development, strong Cx40 expression gradually decreased, while expression of Cx37, Cx43 and Cx45 increased, postnatally showing more equalized expression patterning. In parallel, initially dispersed renin cells localized to JGA, and greatly increased expression in postnatal kidneys. In CNF kidneys, increased levels of Cx43, Cx37 and Cx45 co-localized with accumulations of renin cells in JGA. Additionally, they reappeared in extraglomerular mesangial cells, indicating association between return to embryonic Cxs patterning and pathologically changed kidney tissue. Based on the described Cxs and renin expression patterning, we suggest involvement of Cx40 primarily in the formation of JGA in developing kidneys, while Cx37, Cx43 and Cx45 might participate in JGA signal transfer important for postnatal maintenance of kidney function and blood pressure control.


2019 ◽  
Vol 12 (9) ◽  
pp. e229824
Author(s):  
Andrew T Del Pozzi ◽  
Michael Enechukwu ◽  
Svetlana Blitshteyn

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous autonomic disorder characterised by orthostatic intolerance and a rise in heart rate by at least 30 bpm or an absolute heart rate value of at least 120 bpm within 10 min of standing or during a tilt table test. Overwhelmingly, POTS affects young Caucasian women, which can lead physicians to miss the diagnosis in men or non-white patients. We describe a case of 29-year-old African-American man who developed lightheadedness, generalised weakness, tachycardia and palpitations and was subsequently diagnosed with POTS. We review its clinical features, differential diagnosis, pathophysiology and treatment options. We also emphasise that POTS should be considered as a differential diagnosis in any patient presenting with typical clinical features, who may not be in the usual demographics of the disorder.


1995 ◽  
Vol 269 (2) ◽  
pp. H629-H637 ◽  
Author(s):  
B. N. Van Vliet ◽  
J. E. Hall ◽  
H. L. Mizelle ◽  
J. P. Montani ◽  
M. J. Smith

We investigated why resting heart rate is elevated in dogs fed a high saturated fat diet for 12.7 +/- 1.8 wk. Obese dogs exhibited elevated body weight (59%), blood pressure (14%), and heart rate (25%). Differences in resting heart rate (control, 58 +/- 5 beats/min; obese, 83 +/- 7 beats/min) were abolished after hexamethonium, indicating an autonomic mechanism. Hexamethonium also reduced blood pressure in obese (20 +/- 4 mmHg) but not control (9 +/- 6 mmHg) animals. Propranolol did not affect heart rate in either group, excluding a beta-adrenergic mechanism. Subsequent administration of atropine increased heart rate more in control than in obese dogs (110 +/- 9 vs. 57 +/- 11 beats/min). The sensitivity of the cardiac limb of the baroreflex (Oxford method) was reduced by 46% in the obese group, confirming impairment of the parasympathetic control of heart rate. The standard deviation of blood pressure measurements was normal when expressed as a percentage of the mean arterial blood pressure (control, 11.2 +/- 0.4%; obese, 11.2 +/- 0.5%). Our results indicate that the development of obesity in dogs fed a high saturated fat diet is accompanied by an attenuated resting and reflex parasympathetic control of heart rate.


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