Human skeletal muscle sympathetic nerve activity, heart rate and limb haemodynamics with reduced blood oxygenation and exercise

Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Denmark.
The Journal of Physiology (Impact Factor: 5.04). 09/2003; 551(Pt 2):635-47. DOI: 10.1113/jphysiol.2003.044024
Source: PubMed

ABSTRACT Acute systemic hypoxia causes significant increases in human skeletal muscle sympathetic nerve activity (MSNA), heart rate and ventilation. This phenomenon is thought to be primarily mediated by excitation of peripheral chemoreceptors sensing a fall in arterial free oxygen partial pressure (Pa,O2). We directly tested the role of Pa,O2 on MSNA (peroneal microneurography), heart rate, ventilation and leg haemodynamics (n= 7-8) at rest and during rhythmic handgrip exercise by using carbon monoxide (CO) to mimic the effect of systemic hypoxia on arterial oxyhaemoglobin (≈20 % lower O2Hba), while normalising or increasing Pa,O2 (range 40-620 mmHg). The four experimental conditions were: (1) normoxia (Pa,O2≈110 mmHg; carboxyhaemoglobin (COHb) ≈2 %); (2) hypoxia (Pa,O2≈40 mmHg; COHb ≈2 %); (3) CO + normoxia (Pa,O2≈110 mmHg; COHb ≈23 %); and (4) CO + hyperoxia (Pa,O2≈620 mmHg; COHb ≈24 %). Acute hypoxia augmented sympathetic burst frequency, integrated MSNA, heart rate and ventilation compared to normoxia over the entire protocol (7–13 bursts min−1, 100-118 %, 13-17 beats min−1, 2-4 l min−1, respectively, P < 0.05). The major new findings were: (1) CO + normoxia and CO + hyperoxia also elevated MSNA compared to normoxia (63–144 % increase in integrated MSNA; P < 0.05) but they did not increase heart rate (62–67 beats min−1) or ventilation (6.5–6.8 l min−1), and (2) despite the 4-fold elevation in MSNA with hypoxaemia and exercise, resting leg blood flow, vascular conductance and O2 uptake remained unchanged. In conclusion, the present results suggest that increases in MSNA with CO are not mediated by activation of the chemoreflex, whereas hypoxia-induced tachycardia and hyperventilation are mediated by activation of the chemoreflex in response to the decline in Pa,O2. Our findings also suggest that Pa,O2 is not an obligatory signal involved in the enhanced MSNA with reduced blood oxygenation.

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    • "The study was conducted in the province of British Columbia (BC), on the west coast of Canada. Forest fires burn an average of 980 km2 per year in BC [19], and widespread infestation by the mountain pine beetle has left forests more susceptible to extreme events in recent years [20]. The province is geographically divided into 89 local health areas (LHAs), ranging in size from 40 – 130,000 km2 (Figure 1), and in 2006 population from 542 – 352,783 people [21]. "
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    ABSTRACT: Background Several studies have evaluated the association between forest fire smoke and acute exacerbations of respiratory diseases, but few have examined effects on pharmaceutical dispensations. We examine the associations between daily fine particulate matter (PM2.5) and pharmaceutical dispensations for salbutamol in forest fire-affected and non-fire-affected populations in British Columbia (BC), Canada. Methods We estimated PM2.5 exposure for populations in administrative health areas using measurements from central monitors. Remote sensing data on fires were used to classify the populations as fire-affected or non-fire-affected, and to identify extreme fire days. Daily counts of salbutamol dispensations between 2003 and 2010 were extracted from the BC PharmaNet database. We estimated rate ratios (RR) and 95% confidence intervals (CIs) for each population during all fire seasons and on extreme fire days, adjusted for temperature, humidity, and temporal trends. Overall effects for fire-affected and non-fire-affected populations were estimated via meta-regression. Results Fire season PM2.5 was positively associated with salbutamol dispensations in all fire-affected populations, with a meta-regression RR (95% CI) of 1.06 (1.04-1.07) for a 10 ug/m3 increase. Fire season PM2.5 was not significantly associated with salbutamol dispensations in non-fire-affected populations, with a meta-regression RR of 1.00 (0.98-1.01). On extreme fire days PM2.5 was positively associated with salbutamol dispensations in both population types, with a global meta-regression RR of 1.07 (1.04 - 1.09). Conclusions Salbutamol dispensations were clearly associated with fire-related PM2.5. Significant associations were observed in smaller populations (range: 8,000 to 170,000 persons, median: 26,000) than those reported previously, suggesting that salbutamol dispensations may be a valuable outcome for public health surveillance during fire events.
    Environmental Health 01/2013; 12(1):11. DOI:10.1186/1476-069X-12-11 · 3.37 Impact Factor
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    • "Burst identification was controlled visually by a single investigator. Nerve activity was quantified by determining the burst frequency (bursts per minute) and burst incidence (bursts per 100 heart beats) (Hanada et al. 2003). "
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    ABSTRACT: Young healthy adults exhibit an inverse linear relationship between muscle sympathetic nerve activity (MSNA) and α-adrenergic responsiveness. This balance may be reversed in metabolic syndrome (MetSyn) given animal models exhibit increased sympathetic activity and α-mediated vasoconstriction. We hypothesized humans with MetSyn would demonstrate increased α-adrenergic vasoconstriction and the inverse relationship between MSNA and adrenergic responsiveness would be lost. We measured MSNA (microneurography of the peroneal nerve) and forearm blood flow (FBF, Doppler ultrasound) in 16 healthy control subjects (31±3 years) and 14 adults with MetSyn (35±3 years; p>0.05) during local administration of α-adrenergic agonists (phenylephrine, PE α1; clonidine, CL α2). MSNA was greater in MetSyn subjects when compared with healthy controls (p<0.05). A group difference in vasoconstriction to PE was not detected (p=0.08). The level of α1-mediated vasoconstriction was inversely related to MSNA in control subjects (r=0.5, p=0.04); this balance between MSNA and α1-responsiveness was lost in adults with MetSyn. MetSyn subjects exhibited greater vasoconstriction to CL infusion when compared with healthy controls (p<0.01). A relationship between MSNA and α2-mediated vasoconstriction was not detected in either group. In summary, altered neurovascular control in human MetSyn is receptor-specific. The observed uncoupling between MSNA and α1-adrenergic responsiveness and increased α2 -vasoconstriction may lead to reduced FBF, altered flow distribution, and/or severe hypertension with the progression toward diabetes and cardiovascular disease.
    The Journal of Physiology 10/2012; 590(23). DOI:10.1113/jphysiol.2012.239780 · 5.04 Impact Factor
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    • "Adapted with permission from Hanada et al. (2003). sympatholysis' . "
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    ABSTRACT: Hypoxia can have profound influences on the circulation. In humans, acute exposure to moderate hypoxia has been demonstrated to result in vasodilatation in the coronary, cerebral, splanchnic and skeletal muscle vascular beds. The combination of submaximal exercise and hypoxia produces a "compensatory" vasodilatation and augmented blood flow in contracting skeletal muscles relative to the same level of exercise under normoxic conditions. This augmented vasodilatation exceeds that predicted by a simple sum of the individual dilator responses to hypoxia alone and normoxic exercise. Additionally, this enhanced hypoxic exercise hyperaemia is proportional to the hypoxia-induced fall in arterial oxygen (O2) content, thus preserving muscle O2 delivery and ensuring it is matched to demand. Several vasodilator pathways have been proposed and examined as likely regulators of skeletal muscle blood flow in response to changes in arterial O2 content. The purpose of this review is to put into context the present evidence regarding mechanisms responsible for the compensatory vasodilatation observed during hypoxic exercise in humans. Along these lines, this review will highlight the interactions between various local metabolic and endothelial derived substances that influence vascular tone during hypoxic exercise.
    The Journal of Physiology 09/2012; 590(24). DOI:10.1113/jphysiol.2012.242396 · 5.04 Impact Factor
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