Central and peripheral chemoreflexes in humans with treated hypertension.

Increased peripheral chemoreflex sensitivity is a pathogenic feature of human hypertension (HTN), while both central and peripheral chemoreflex sensitivities are reportedly augmented in animal models of HTN. Herein, we tested the hypothesis that both central and combined central and peripheral chemoreflex sensitivities are augmented in HTN. Fifteen HTN participants (68 ± 5 years; mean ± SD) and 13 normotensives (NT; 65 ± 6 years) performed two modified rebreathing protocols in which the partial pressure of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\rm{ETC}}{{\rm{O}}_2}}}$ ) progressively increased while the partial pressure of end-tidal oxygen was clamped at either 150 mmHg (isoxic hyperoxia; central chemoreflex activation) or 50 mmHg (isoxic hypoxia; combined central and peripheral chemoreflex activation). Ventilation ( V ̇ E ${\dot{V}}_{\rm{E}}$ ; pneumotachometer) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded, and ventilatory ( V ̇ E ${\dot{V}}_{\rm{E}}$ vs. P ETC O 2 ${P_{{\rm{ETC}}{{\rm{O}}_2}}}$  slope) and sympathetic (MSNA vs. P ETC O 2 ${P_{{\rm{ETC}}{{\rm{O}}_2}}}$ slope) chemoreflex sensitivities and recruitment thresholds (breakpoint) were calculated. Global cerebral blood flow (gCBF; duplex Doppler) was measured, and the association with chemoreflex responses was examined. Central ventilatory and sympathetic chemoreflex sensitivities were greater in HTN than NT (2.48 ± 1.33 vs. 1.58 ± 0.42 L min-1  mmHg-1 , P = 0.030: 3.32 ± 1.90 vs. 1.77 ± 0.62 a.u. mmHg-1 , P = 0.034, respectively), while recruitment thresholds were not different between groups. HTN and NT had similar combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities and recruitment thresholds. A lower gCBF was associated with an earlier recruitment threshold for V ̇ E ${\dot{V}}_{\rm{E}}$ (R2  = 0.666, P < 0.0001) and MSNA (R2  = 0.698, P = 0.004) during isoxic hyperoxic rebreathing. These findings indicate that central ventilatory and sympathetic chemoreflex sensitivities are augmented in human HTN and perhaps suggest that targeting the central chemoreflex may help some forms of HTN. KEY POINTS: In human hypertension (HTN) increased peripheral chemoreflex sensitivity has been identified as a pathogenic feature, and in animal models of HTN, both central and peripheral chemoreflex sensitivities are reportedly augmented. In this study, the hypothesis was tested that both central and combined central and peripheral chemoreflex sensitivities are augmented in human HTN. We observed that both central ventilatory and sympathetic chemoreflex sensitivities were augmented in HTN compared to age-matched normotensive controls, but no difference was found in the combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities. During central chemoreflex activation, the ventilatory and sympathetic recruitment thresholds were lower in those with lower total cerebral blood flow. These results indicate a potential contributory role of the central chemoreceptors in the pathogenesis of human HTN and support the possibility that therapeutic targeting of the central chemoreflex may help some forms of HTN.

Venous capacity and compliance in hypertensive adults: influence of hypoxia and hyperoxia.

In hypertension, the cardiorespiratory responses to peripheral chemoreflex activation (hypoxia) and inactivation (hyperoxia) are reportedly augmented, but the impact on peripheral venous function is unknown. We tested the hypothesis that in hypertensives, both hypoxia and hyperoxia evoke more pronounced changes in lower limb venous capacity and compliance, than in age-matched normotensives. In 10 hypertensive [HTN: 7 women; age: 71.7 ± 3.7 yr, mean blood pressure (BP): 101 ± 10 mmHg, mean ± SD] and 11 normotensive (NT: 6 women; age: 67.7 ± 8.0 yr, mean BP 89 ± 11 mmHg) participants, great saphenous vein cross-sectional area (GSV CSA; Doppler ultrasound) was measured during a standard 60 mmHg thigh cuff inflation-deflation protocol. Separate conditions of room air, hypoxia [fraction of inspired oxygen ([Formula: see text]): 0.10] and hyperoxia ([Formula: see text]: 0.50) were tested. In HTN, GSV CSA was decreased in hypoxia (5.6 ± 3.7 mm2, P = 0.041) compared with room air (7.3 ± 6.9 mm2), whereas no change was observed with hyperoxia (8.0 ± 9.1 mm2, P = 0.988). In NT, no differences in GSV CSA were observed between any condition (P = 0.299). Hypoxia enhanced GSV compliance in HTN (-0.0125 ± 0.0129 vs. -0.0288 ± 0.0090 mm2·100 mm2·mmHg-1, room air vs. hypoxia, respectively; P = 0.004), but it was unchanged in NT (-0.0139 ± 0.0121 vs. -0.0093 ± 0.0066 mm2·100 mm2·mmHg-1, room air vs. hypoxia, respectively; P < 0.541). Venous compliance was unaltered with hyperoxia in both groups (P < 0.05). In summary, compared with NT, hypoxia elicits a decrease in GSV CSA and enhanced GSV compliance in HTN, indicating enhanced venomotor responsiveness to hypoxia.NEW & NOTEWORTHY Hypertension remains a significant global health problem. Although hypertension research and therapies are keenly focused on the heart and arterial circulation, the venous circulation has been neglected comparatively. We determined whether hypoxia, known to cause peripheral chemoreflex activation, evoked more pronounced changes in lower limb venous capacity and compliance in hypertensives (HTN) than in age-matched normotensives (NT). We found that hypoxia reduced venous capacity in the great saphenous vein in HTN and increased its compliance twofold. However, hypoxia did not affect venous function in NT. Our data indicate the venomotor response to hypoxia is enhanced in hypertension, and this may contribute to the hypertensive state.

Sex differences in the sympathetic neurocirculatory responses to chemoreflex activation.

The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29 ± 6 years, 22.8 ± 2.4 kg/m2 : mean ± SD) and 10 men (30 ± 7 years, 24.8 ± 3.2 kg/m2 ) undertook randomized 5 min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O2 ); peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO2 ), 50% O2 ; central chemoreflex activation) and hypercapnic hypoxia (7% CO2 , 10% O2 ; central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; finger photoplethysmography) and minute ventilation ( V̇$\dot{\rm{V}}$E ; pneumotachometer) were measured. Total MSNA (P = 1.000 and P = 0.616), MAP (P = 0.265) and V̇$\dot{\rm{V}}$E (P = 0.587 and P = 0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in V̇$\dot{\rm{V}}$E during hypercapnic hyperoxia (27.3 ± 6.3 vs. 39.5 ± 7.5 l/min, P < 0.0001) and hypercapnic hypoxia (40.9 ± 9.1 vs. 53.8 ± 13.3 l/min, P < 0.0001) compared with men. However, total MSNA responses were augmented in women (hypercapnic hyperoxia 378 ± 215 vs. 258 ± 107%, P = 0.017; hypercapnic hypoxia 607 ± 290 vs. 362 ± 268%, P < 0.0001). No sex differences in total MSNA, MAP or V̇$\dot{\rm{V}}$E were observed during isocapnic hyperoxia and hypocapnic hyperoxia. Our results indicate that young women have augmented sympathetic responses to central chemoreflex activation, which explains the augmented MSNA response to combined central and peripheral chemoreflex activation. KEY POINTS: Sex differences in the control of breathing have been well studied, but whether there are differences in the sympathetic neurocirculatory responses to chemoreflex activation between healthy women and men is incompletely understood. We observed that, compared with young men, young women displayed augmented increases in muscle sympathetic nerve activity during both hypercapnic hyperoxia (central chemoreflex activation) and hypercapnic hypoxia (central and peripheral chemoreflex activation) but had attenuated increases in minute ventilation. In contrast, no sex differences were found in either muscle sympathetic nerve activity or minute ventilation responses to isocapnic hypoxia (peripheral chemoreceptor stimulation). Young women have blunted ventilator, but augmented sympathetic responses, to central (hypercapnic hyperoxia) and combined central and peripheral chemoreflex activation (hypercapnic hypoxia), compared with young men. The possible causative association between the reduced ventilation and heightened sympathetic responses in young women awaits validation.

Effects of hypoxia and hyperoxia on venous capacity and compliance in healthy men and women.

Blood oxygen is an important modulator of arterial function, but its impact on peripheral venous function is incompletely understood. Herein, we sought to determine the effect of hypoxia and hyperoxia on venous capacity and compliance in the lower limb. In 16 healthy individuals (7 women; age: 28.3 ± 7.6 yr, mean ± SD), we assessed peripheral oxygen saturation ([Formula: see text]), the cross-sectional area (CSA) of the great saphenous vein (GSV; Doppler ultrasound), and calf volume (strain-gauge plethysmography) during a standard 60 mmHg thigh cuff inflation-deflation protocol. Separate trials were undertaken during breathing of room air, hypoxia [fraction in inspired oxygen ([Formula: see text]): 0.10], and hyperoxia ([Formula: see text]: 0.50), according to a single-blinded, randomized design. Lower limb pressure-CSA and pressure-volume relationships were modeled using a quadratic regression equation and compliance derived. [Formula: see text] was decreased by hypoxia (83.6 ± 5.6%) and increased by hyperoxia (98.7 ± 0.5%) compared with room air (96.4 ± 1.0%, P < 0.001). Compared with room air (17.0 ± 7.9 mm2), hypoxia decreased GSV CSA (13.4 ± 5.7 mm2, P < 0.001), whereas no change was observed with hyperoxia (17.1 ± 8.7 mm2, P = 0.883). GSV compliance derived from the pressure-CSA relationships was elevated approximately twofold with hyperoxia (-0.0061 ± 0.0046 a.u.) when compared with room air (-0.0029 ± 0.002 a.u., P = 0.027) and hypoxia (-0.0030 ± 0.0032 a.u., P = 0.007). No differences were observed in calf pressure-volume parameters with either hypoxia or hyperoxia (P > 0.05). Our data indicate that GSV capacity is reduced by hypoxia, and that GSV compliance is increased by hyperoxia, thus highlighting the often overlooked role of oxygen in the regulation of venous circulation.

Are our medical graduates in New Zealand safe and accurate in ECG interpretation?

AIM: We aimed to assess the skills of final year medical students and resident medical officers in recognising and interpreting important common or life-threatening abnormalities in the electrocardiogram (ECG). METHODS: 102 participants at two study sites (52 of whom were final year medical students) attempted to determine the heart rate and rhythm and identify and interpret any abnormalities present in 15 ECGs in a 30-minute time period. RESULTS: Accurate determination of heart rate was poor, ranging from 0% to 89% correct across the 15 ECGs. Normal sinus rhythm in 8 ECGs was identified 81% to 95% of the time, and ventricular tachycardia was identified by 98% of participants. Atrial fibrillation (55%), second degree heart block (19%) and ventricular pacing (9%) were not well identified. Four ECGs showed acute ischaemic ST segment changes, and these were correctly identified in 87% to 93% of cases, although interpretation of these abnormalities was less accurate. Long QT interval (7%) and pre-excitation (WPW pattern, 11%) were not well recognised. Nearly half of the participants rated their ability to interpret ECGs as less than satisfactory while just over half rated the ECG teaching they had received as less than satisfactory. CONCLUSIONS: Overall study participants did not achieve what we would consider an adequate standard in recognising and interpreting important common or life-threatening abnormalities in the ECG. To address this we need to define minimum standards in ECG interpretation, to improve our teaching to meet these standards, and to assess our graduates against these.

Aldosterone and left ventricular hypertrophy in Afro-Caribbean subjects with low renin hypertension.

BACKGROUND: Activity of the renin-angiotensin-aldosterone system is thought to play a major role in determining blood pressure (BP) and target organ damage such as left ventricular hypertrophy. In Afro-Caribbean subjects, however, hypertension tends to be more severe despite lower plasma renin activity. We investigated whether this might be due to a different relation between aldosterone and renin in Afro-Caribbean compared to white subjects. METHODS: Plasma aldosterone and renin activity were assessed in the morning after 15 min seated in 383 hypertensive subjects of Afro-Caribbean or white ethnicity (61% Afro-Caribbean, 83% on treatment) attending a hypertension clinic in London, UK. Left ventricular mass index (LVMI) was assessed by echocardiography in 276 subjects. RESULTS: Plasma renin activity was lower in Afro-Caribbean compared to white subjects (0.4 [0.3-1.0] v 1.4 [0.5-3.4] ng/mL/h, medians [interquartile range], P < .0001). Despite this, aldosterone was higher in Afro-Caribbean compared to white subjects (8.0 [6.1-12.6] v 7.4 [2.3-17.1] ng/dL, medians [interquartile range], P < .01). The LVMI corrected for sex and BP was higher in Afro-Caribbean than in white subjects. In Afro-Caribbean but not in white subjects LVMI was independently correlated with plasma aldosterone (standardized regression coefficient, beta= 0.25, P < .001). CONCLUSIONS: In Afro-Caribbean hypertensive subjects in London, plasma aldosterone is elevated despite lower renin and may contribute to increased severity of hypertension and left ventricular hypertrophy in Afro-Caribbean compared to white subjects.