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HEREDITARY SPHEROCYTOSIS DUE TO A NOVEL VARIANT, P.Q1034X, IN THE BETA SUBUNIT OF THE SPECTRIN GENE [Meeting Abstract]
Afridi, Faraz; Van Helmond, Jennifer; Ahmed, Rafat; Ganesh, Jaya
ISI:000530720700103
ISSN: 1545-5009
CID: 5476052
HYPOFIBRINOGENEMIA DUE TO A NOVEL FGG MISSENSE MUTATION PRESENTING IN A FAMILY [Meeting Abstract]
Van Helmond, Jennifer; Kennedy, Samantha; Scarano, Irene; Ahmed, Rafat
ISI:000490282100474
ISSN: 1545-5009
CID: 5476042
ATYPICAL PRESENTATION OF WISKOTT ALDRICH SYNDROME IN AN INFANT [Meeting Abstract]
Van Helmond, Jennifer; Ganesh, Jaya; Ahmed, Rafat
ISI:000490282100395
ISSN: 1545-5009
CID: 5476032
Investigating cerebral blood flow control to save the newborn brain [Comment]
Murali, Vignesh; Freeman, Cecilia G; Harvey, Ronée E; Baig, Nicole C; van Helmond, Jennifer L; van Helmond, Noud
PMID: 30265744
ISSN: 1469-7793
CID: 5475992
Effect of bilateral carotid body resection on cardiac baroreflex control of blood pressure during hypoglycemia
Limberg, Jacqueline K; Taylor, Jennifer L; Mozer, Michael T; Dube, Simmi; Basu, Ananda; Basu, Rita; Rizza, Robert A; Curry, Timothy B; Joyner, Michael J; Wehrwein, Erica A
Hypoglycemia results in a reduction in cardiac baroreflex sensitivity and a shift in the baroreflex working range to higher heart rates. This effect is mediated, in part, by the carotid chemoreceptors. Therefore, we hypothesized hypoglycemia-mediated changes in baroreflex control of heart rate would be blunted in carotid body-resected patients when compared with healthy controls. Five patients with bilateral carotid body resection for glomus tumors and 10 healthy controls completed a 180-minute hyperinsulinemic, hypoglycemic (≈3.3 mmol/L) clamp. Changes in heart rate, blood pressure, and spontaneous cardiac baroreflex sensitivity were assessed. Baseline baroreflex sensitivity was not different between groups (P>0.05). Hypoglycemia resulted in a reduction in baroreflex sensitivity in both the groups (main effect of time, P<0.01) and responses were lower in resected patients when compared with controls (main effect of group, P<0.05). Hypoglycemia resulted in large reductions in systolic (-17±7 mm Hg) and mean (-14±5 mm Hg) blood pressure in resected patients that were not observed in controls (interaction of group and time, P<0.05). Despite lower blood pressures, increases in heart rate with hypoglycemia were blunted in resected patients (interaction of group and time, P<0.01). Major novel findings from this study demonstrate that intact carotid chemoreceptors are essential for increasing heart rate and maintaining arterial blood pressure during hypoglycemia in humans. These data support a contribution of the carotid chemoreceptors to blood pressure control and highlight the potential widespread effects of carotid body resection in humans.
PMCID:4507506
PMID: 25870188
ISSN: 1524-4563
CID: 5477362
Effect of bilateral carotid body resection on the counterregulatory response to hypoglycaemia in humans
Wehrwein, Erica A; Limberg, Jacqueline K; Taylor, Jennifer L; Dube, Simmi; Basu, Ananda; Basu, Rita; Rizza, Robert A; Curry, Timothy B; Joyner, Michael J
What is the central question of this study? Hyperoxia blunts hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in carotid body-resected patients; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. What is the main finding and its importance? Our data indicate that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, a relatively normal counterregulatory response to hypoglycaemia in carotid body-resected patients highlights: (i) the potential for long-term adaptations after carotid body resection; and (ii) the importance of redundant mechanisms in mediating hypoglycaemia counterregulation. Hyperoxia reduces hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in patients with bilateral carotid body resection; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. Five patients (three male and two female) with bilateral carotid body resection for glomus tumours underwent two 180 min hyperinsulinaemic, hypoglycaemic (∼ 3.3 mmol l(-1)) clamps separated by a minimum of 1 week and randomized to either normoxia (21% fractional inspired O2 ) or hyperoxia (100% fractional inspired O2). Ten healthy adults (seven male and three female) served as control subjects. Hypoglycaemia counterregulation in carotid body-resected patients was not significantly altered by hyperoxia (area under the curve expressed as a percentage of the normoxic response: glucose infusion rate, 111 ± 10%; cortisol, 94 ± 6%; glucagon, 107 ± 7%; growth hormone, 92 ± 10%; adrenaline, 89 ± 26%; noradrenaline, 79 ± 15%; main effect of condition, P > 0.05). This is in contrast to previously published results from healthy adults. However, the counterregulatory responses to hypoglycaemia during normoxia were not impaired in carotid body-resected patients when compared with control subjects (main effect of group, P > 0.05). Our data provide further corroborative evidence that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, relatively normal counterregulatory responses to hypoglycaemia in carotid body-resected patients highlight the importance of redundant mechanisms in mediating hypoglycaemia counterregulation.
PMID: 25557731
ISSN: 1469-445x
CID: 5477352
Effect of vitamin C on hyperoxia-induced vasoconstriction in exercising skeletal muscle
Ranadive, Sushant M; Joyner, Michael J; Walker, Branton G; Taylor, Jennifer L; Casey, Darren P
Hyperoxia can cause substantial reductions in peripheral and coronary blood flow at rest and during exercise, which may be caused by reactive oxygen species (ROS) generated during hyperoxia. The aim of this study was to investigate the role of ROS in hyperoxia-induced reductions in skeletal muscle blood flow during forearm exercise. We hypothesized that infusion of vitamin C would abolish the effects of hyperoxia on the forearm blood flow (FBF) responses to exercise. Twelve young healthy adults performed rhythmic forearm handgrip exercise (10% of maximum voluntary contraction for 5 min) during normoxia and hyperoxia. For each condition, two trials were conducted with intra-arterial administration of saline or vitamin C. FBF was measured using Doppler ultrasound. During hyperoxia with saline, FBF and forearm vascular conductance (FVC) were 86.3 ± 5.1 and 86.8 ± 5.2%, respectively, of the normoxic values (100%) (P < 0.05). During vitamin C, hyperoxic FBF and FVC responses were 90.9 ± 4.2 and 90.9 ± 4.1%, respectively, of the normoxic values (P = 0.57 and 0.59). Subjects were then divided into three subgroups based on their percent decrease in FBF (>20, 10-20, and <10%) during hyperoxia. In the subgroup that demonstrated the greatest hyperoxia-induced changes (>20%), FBF and FVC during hyperoxia were 67.1 ± 4.0 and 66.8 ± 3.6%, respectively, of the normoxic values. Vitamin C abolished these effects on FBF and FVC with values that were 102.0 ± 5.2 and 100.8 ± 6.1%, respectively. However, vitamin C had no effect in the other two subgroups. This analysis is consistent with the idea that ROS generation blunts the FBF responses to exercise in the subjects most affected by hyperoxia.
PMCID:4233251
PMID: 25237186
ISSN: 1522-1601
CID: 5477342
The effect of ageing and indomethacin on forearm reactive hyperaemia in healthy adults
Taylor, Jennifer L; Hines, Casey N; Nicholson, Wayne T; Joyner, Michael J; Barnes, Jill N
We have previously shown that non-selective cyclo-oxygenase inhibition, via indomethacin, unfavourably increased central blood pressure in older adults, with little effect in young adults. In addition, the vasoactive prostaglandins have been shown to contribute to both peripheral vasodilator responses and large artery function; however, there is little information available in older adults and conflicting reports in young adults on the extent to which resistance vessel function is influenced by indomethacin. Thus, we tested the hypothesis that cyclo-oxygenase inhibition using indomethacin would attenuate forearm vascular conductance during reactive hyperaemia in older adults compared with young adults. Forearm blood flow responses to 5 min of forearm ischaemia were measured in 26 healthy adults (13 young, 25 ± 5 years old; and 13 older, 65 ± 6 years old), using venous occlusion plethysmography before and after indomethacin. Baseline forearm blood flow and vascular conductance were not different between groups during either trial, and there were no age-related differences prior to cyclo-oxygenase inhibition. Peak forearm vascular conductance and blood flow were similar between groups before indomethacin, but lower in older adults after indomethacin compared with young adults (27 ± 4 versus 41 ± 4 ml (100 ml)(-1) min(-1) (100 mmHg)(-1), P = 0.02; and 23 ± 3 versus 33 ± 3 ml (100 ml)(-1) min(-1), P = 0.02, respectively). These results, in conjunction with our previous findings in large arteries, suggest that ageing alters the effect of cyclo-oxygenase inhibition on vascular responses, and specifically, the resistance vessel responses underlying reactive hyperaemia.
PMCID:6371398
PMID: 24706194
ISSN: 1469-445x
CID: 5477332
Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans
Limberg, Jacqueline K; Taylor, Jennifer L; Dube, Simmi; Basu, Rita; Basu, Ananda; Joyner, Michael J; Wehrwein, Erica A
Activation of the carotid body chemoreceptors with hypoxia alters baroreceptor-mediated responses. We aimed to examine whether this relationship can be translated to other chemoreceptor stimuli (i.e. hypoglycaemia) by testing the following hypotheses: (i) activation of the carotid body chemoreceptors with hypoglycaemia would reduce spontaneous cardiac baroreflex sensitivity (sCBRS) in healthy humans; and (ii) desensitization of the carotid chemoreceptors with hyperoxia would restore sCBRS to baseline levels during hypoglycaemia. Ten young healthy adults completed two 180 min hyperinsulinaemic [2 mU (kg fat-free mass)(-1) min(-1)], hypoglycaemic (∼ 3.2 μmol ml(-1)) clamps, separated by at least 1 week and randomized to normoxia (arterial partial pressure of O2, 122 ± 10 mmHg) or hyperoxia (arterial partial pressure of O2, 424 ± 123 mmHg; to blunt activation of the carotid body glomus cells). Changes in heart rate, blood pressure, plasma catecholamines, heart rate variability (HRV) and sCBRS were assessed. During hypoglycaemia, HRV and sCBRS were reduced (P < 0.05) and the baroreflex working range was shifted to higher heart rates. When hyperoxia was superimposed on hypoglycaemia, there was a greater reduction in blood pressure and a blunted rise in heart rate when compared with normoxic conditions (P < 0.05); however, there was no detectable effect of hyperoxia on sCBRS or HRV during hypoglycaemia (P > 0.05). In summary, hypoglycaemia-mediated changes in HRV and sCBRS cannot be attributed exclusively to the carotid chemoreceptors; however, the chemoreceptors appear to play a role in resetting the baroreflex working range during hypoglycaemia.
PMCID:4227537
PMID: 24414173
ISSN: 1469-445x
CID: 5477322
Acute effects of a mixed meal on arterial stiffness and central hemodynamics in healthy adults
Taylor, Jennifer L; Curry, Timothy B; Matzek, Luke J; Joyner, Michael J; Casey, Darren P
BACKGROUND:Elevated central pressures and arterial stiffness are associated with increased peripheral resistance and higher sympathetic nervous system activity. Additionally, consumption of a meal is known to be sympathoexcitatory. However, the acute effects of a meal on aortic wave reflection and stiffness are unknown. Therefore, we tested the hypothesis that aortic wave reflection and stiffness would increase after a meal. METHODS:We examined these effects using high-fidelity radial arterial pressure waveforms and carotid-femoral pulse wave velocity measured noninvasively by applanation tonometry before and 60 and 180 minutes after ingestion of a liquid mixed meal (Ensure; 40% of daily energy expenditure) in 17 healthy adults (9 men/8 women; aged 29 ± 2 years). Additionally, we measured sympathetic activity by microneurography at baseline and up to 60 minutes after the meal. RESULTS:Although sympathetic activity increased after the meal, both peripheral and central pressures were reduced at 180 minutes from baseline (all P < 0.05). Contrary to our hypothesis, augmentation index (14% ± 3% vs. 2% ± 3% vs. 8% ± 3%), augmentation index normalized for heart rate (8% ± 3% vs. -3% ± 3% vs. 3% ± 3%), augmented pressure (5 ± 1 mm Hg vs. 1 ± 1 mm Hg vs. 3 ± 1 mm Hg), and pulse wave velocity (7.1 ± 0.2 m/s vs. 6.7 ± 0.2 m/s vs. 6.7 ± 0.1 m/s) were substantially reduced at 60 and 180 minutes after the meal (all P < 0.05). CONCLUSIONS:Taken together, our results suggest that a liquid mixed meal acutely decreases central hemodynamics and arterial stiffness in healthy adults, which may be a result of meal-related increases in insulin and/or visceral vasodilation.
PMCID:3915744
PMID: 24242825
ISSN: 1941-7225
CID: 5477312