Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise

Peak oxygen uptake (V˙o 2 peak) in patients with heart failure (HF) is inversely related to muscle sympathetic nerve activity (MSNA) at rest. We hypothesized that the MSNA response to handgrip exercise is augmented in HF patients and is greatest in those with lowV˙o 2 peak. We studied 14 HF patients and 10 age-matched normal subjects during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50% MVC) handgrip exercise that was followed by 2 min of posthandgrip ischemia (PHGI). MSNA was significantly increased during exercise in HF but not normal subjects. Both MSNA and HF levels remained significantly elevated during PHGI after 30% isometric and 50% isotonic handgrip in HF but not normal subjects. HF patients with lower V˙o 2 peak (<56% predicted; n = 8) had significantly higher MSNA during rest and exercise than patients withV˙o 2 peak > 56% predicted ( n = 6) and normal subjects. The muscle metaboreflex contributes to the greater reflex increase in MSNA during ischemic or intense nonischemic exercise in HF. This occurs at a lower threshold than normal and is a function ofV˙o 2 peak.

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Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.3.h1312 ◽

2001 ◽

Vol 281 (3) ◽

pp. H1312-H1318 ◽

Cited By ~ 35

Author(s):

C. F. Notarius ◽

D. J. Atchison ◽

G. A. Rongen ◽

J. S. Floras

Keyword(s):

Heart Failure ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Normal Subjects ◽

Voluntary Contraction ◽

Receptor Blockade ◽

Handgrip Exercise ◽

Muscle Metaboreflex ◽

Sympathetic Response ◽

Isotonic Exercise

Adenosine (Ado) increases muscle sympathetic nerve activity (MSNA) reflexively. Plasma Ado and MSNA are elevated in heart failure (HF). We tested the hypothesis that Ado receptor blockade by caffeine would attenuate reflex MSNA responses to handgrip (HG) and posthandgrip ischemia (PHGI) and that this action would be more prominent in HF subjects than in normal subjects. We studied 12 HF subjects and 10 age-matched normal subjects after either saline or caffeine (4 mg/kg) infusion during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50%) HG exercise, followed by 2 min of PHGI. In normal subjects, caffeine did not block increases in MSNA during PHGI after 50% HG. In HF subjects, caffeine abolished MSNA responses to PHGI after both isometric and 50% isotonic exercise ( P < 0.05) but MSNA responses during HG were unaffected. These findings are consistent with muscle metaboreflex stimulation by endogenous Ado during ischemic or intense nonischemic HG in HF and suggest an important sympathoexcitatory role for endogenous Ado during exercise in this condition.

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Forearm elevation augments sympathetic activation during handgrip exercise in humans

Clinical Science ◽

10.1042/cs1030295 ◽

2002 ◽

Vol 103 (3) ◽

pp. 295-301 ◽

Cited By ~ 5

Author(s):

Daisaku MICHIKAMI ◽

Atsunori KAMIYA ◽

Qi FU ◽

Yuki NIIMI ◽

Satoshi IWASE ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Muscle Sympathetic Nerve Activity ◽

Voluntary Contraction ◽

Sympathetic Activation ◽

Handgrip Exercise ◽

Excitatory Effect ◽

Muscle Metaboreflex ◽

Forearm Exercise ◽

Exercise In Humans

Although angina pectoris in patients with coronary heart disease often occurs when their forearms are in an elevated position for a prolonged period, and sympathetic activation is a major cause of this condition, little is known about the physiological effects of forearm elevation on sympathetic activity during forearm exercise. We hypothesized that forearm elevation augments sympathetic activation during the static handgrip exercise in humans. A total of 10 healthy male volunteers performed 2min of static handgrip exercise at 30% of maximal voluntary contraction followed by 2min of post-exercise muscle ischaemia (PEMI; specific activation of the muscle metaboreflex) with two forearm positions: the exercising forearm was elevated 50cm above the heart (forearm-elevated trial) or fixed at the level of the heart (heart-level trial). Muscle sympathetic nerve activity (MSNA), blood pressure and heart rate were monitored. MSNA increased during handgrip exercise in both forearm positions (P<0.001); the increase was 51% greater in the forearm-elevated trial (516±99 arbitrary units) than in the heart-level trial (346±44units; P<0.05). The increase in mean blood pressure was 8.4mmHg greater during exercise in the forearm-elevated trial (P<0.05), while changes in heart rate were similar in both forearm positions. The increase in MSNA during PEMI was 71% greater in the forearm-elevated trial (393±71 arbitrary units/min) than in the heart-level trial (229±29units/min; P<0.05). These results support the hypothesis that forearm elevation augments sympathetic activation during handgrip exercise. The excitatory effect of forearm elevation on exercising MSNA may be mediated primarily by increased activation of the muscle metaboreflex.

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Resting muscle sympathetic nerve activity and peak oxygen uptake in heart failure and normal subjects

European Heart Journal ◽

10.1053/euhj.1998.1447 ◽

1999 ◽

Vol 20 (12) ◽

pp. 880-887 ◽

Cited By ~ 45

Author(s):

C Notarius

Keyword(s):

Heart Failure ◽

Oxygen Uptake ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Normal Subjects ◽

Peak Oxygen Uptake ◽

Nerve Activity ◽

Resting Muscle

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Interindividual variability in muscle sympathetic responses to static handgrip in young men: evidence for sympathetic responder types?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00266.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. R114-R121 ◽

Cited By ~ 5

Author(s):

Anthony V. Incognito ◽

Connor J. Doherty ◽

Jordan B. Lee ◽

Matthew J. Burns ◽

Philip J. Millar

Keyword(s):

Blood Pressure ◽

Diastolic Blood Pressure ◽

Interindividual Variability ◽

Muscle Sympathetic Nerve Activity ◽

Voluntary Contraction ◽

Response Patterns ◽

Arterial Baroreflex ◽

Muscle Metaboreflex ◽

Time To Peak ◽

Pressure Time

Negative and positive muscle sympathetic nerve activity (MSNA) responders have been observed during mental stress. We hypothesized that similar MSNA response patterns could be identified during the first minute of static handgrip and contribute to the interindividual variability throughout exercise. Supine measurements of multiunit MSNA (microneurography) and continuous blood pressure (Finometer) were recorded in 29 young healthy men during the first (HG1) and second (HG2) minute of static handgrip (30% maximal voluntary contraction) and subsequent postexercise circulatory occlusion (PECO). Responders were identified on the basis of differences from the typical error of baseline total MSNA: 7 negative, 12 positive, and 10 nonresponse patterns. Positive responders demonstrated larger total MSNA responses during HG1 ( P < 0.01) and HG2 ( P < 0.0001); however, the increases in blood pressure throughout handgrip exercise were similar between all groups, as were the changes in heart rate, stroke volume, cardiac output, total vascular conductance, and respiration (all P > 0.05). Comparing negative and positive responders, total MSNA responses were similar during PECO ( P = 0.17) but opposite from HG2 to PECO (∆40 ± 46 vs. ∆-21 ± 62%, P = 0.04). Negative responders also had a shorter time-to-peak diastolic blood pressure during HG1 (20 ± 20 vs. 44 ± 14 s, P < 0.001). Total MSNA responses during HG1 were associated with responses to PECO ( r = 0.39, P < 0.05), the change from HG2 to PECO ( r = −0.49, P < 0.01), and diastolic blood pressure time to peak ( r = 0.50, P < 0.01). Overall, MSNA response patterns during the first minute of static handgrip contribute to interindividual variability and appear to be influenced by differences in central command, muscle metaboreflex activation, and rate of loading of the arterial baroreflex.

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I027 Circulating levels of cardiac natriuretic peptides measured by highly sensitive and specific IRMA methods in normal subjects and in patients with heart failure

American Journal of Hypertension ◽

10.1016/s0895-7061(97)91353-4 ◽

1998 ◽

Vol 11 (4) ◽

pp. 174A

Author(s):

A CLERICO

Keyword(s):

Heart Failure ◽

Natriuretic Peptides ◽

Normal Subjects ◽

Highly Sensitive ◽

Patients With Heart Failure ◽

Cardiac Natriuretic Peptides ◽

Circulating Levels

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Abstract 266: Neural Circulatory Responses to Isolated Muscle Metaboreflex Activation in Postmenopausal Women

Hypertension ◽

10.1161/hyp.62.suppl_1.a266 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Jody L Greaney ◽

Evan L Matthews ◽

Paul J Fadel ◽

William B Farquhar ◽

Megan M Wenner

Keyword(s):

Blood Pressure ◽

Postmenopausal Women ◽

Young Women ◽

Blood Pressure Response ◽

Muscle Sympathetic Nerve Activity ◽

Feedback Mechanism ◽

Voluntary Contraction ◽

Pressure Response ◽

Isometric Handgrip ◽

Muscle Metaboreflex

Understanding the neural circulatory responses to exercise in postmenopausal women (PMW) is important given their greater risk for developing hypertension. During exercise, blood pressure is controlled, in part, by the exercise pressor reflex, which is a feedback mechanism originating in skeletal muscle and compromised of mechanically and metabolically sensitive afferents. A recent study reported an enhanced blood pressure response during exercise in normotensive PMW due to greater muscle metaboreflex activation, but the mechanism(s) underlying these responses are unknown. Herein, we tested the hypothesis that metaboreflex activation elicits exaggerated sympathetic nervous system responses in PMW compared to young women, contributing to the enhanced blood pressure response during exercise. Methods: Blood pressure (BP, Finometer) and muscle sympathetic nerve activity (MSNA, peroneal microneurography) were continuously measured in 7 PMW (age 59±2 years; BMI 24±1 kg/m 2 ) and 7 young women (age 23±2 years; BMI 22±2 kg/m 2 ) during 2-minutes of isometric handgrip exercise performed at 30% of maximal voluntary contraction followed by 3-minutes of forearm ischemia (post-exercise ischemia, PEI) to isolate muscle metaboreflex activation. Results: Resting mean arterial pressure (MAP) was similar between PMW (85±3 mmHg) and young women (82±2 mmHg; P>0.05). During exercise, the increase in MAP was greater in PMW (Δ18±2mmHg) compared to young women (Δ 12±2 mmHg; P<0.05), and this was maintained during PEI (Δ13±1 mmHg PMW vs. Δ 6±1 mmHg young women; P<0.05). Resting MSNA was higher in PMW (24±4 bursts/min) compared to young women (9±3 bursts/min; P<0.05). Interestingly, the increase in MSNA during exercise was comparable between groups (P>0.05), whereas during PEI, the increase in MSNA was approximately 50% greater in PMW compared to young women (Δ13±2 burst/min PMW vs. 7±2 bursts/min young women; P<0.05). Conclusions: These preliminary data suggest that compared to young women, PMW exhibit an exaggerated MSNA response to isolated muscle metaboreflex activation.

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Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.5.1551 ◽

1998 ◽

Vol 84 (5) ◽

pp. 1551-1559 ◽

Cited By ~ 67

Author(s):

David H. Silber ◽

Greg Sutliff ◽

Qing X. Yang ◽

Michael B. Smith ◽

Lawrence I. Sinoway ◽

...

Keyword(s):

Heart Failure ◽

Matched Control ◽

Circulatory Arrest ◽

Voluntary Contraction ◽

Control Group ◽

Resonance Spectroscopy ◽

Muscle Metaboreflex ◽

Separate Control ◽

Forearm Exercise ◽

Exercise Induced

In congestive heart failure (CHF), the mechanisms of exercise-induced sympathoexcitation are poorly defined. We compared the responses of sympathetic nerve activity directed to muscle (MSNA) and to skin (SSNA, peroneal microneurography) during rhythmic handgrip (RHG) at 25% of maximal voluntary contraction and during posthandgrip circulatory arrest (PHG-CA) in CHF patients with those of an age-matched control group. During RHG, the CHF patients fatigued prematurely. At end exercise, the increase in MSNA was similar in both groups (CHF patients, n = 12; controls, n = 10). However, during PHG-CA, in the controls MSNA returned to baseline, whereas it remained elevated in CHF patients ( P < 0.05). Similarly, at end exercise, the increase in SSNA was comparable in both groups (CHF patients, n = 11; controls, n = 12), whereas SSNA remained elevated during PHG-CA in CHF patients but not in the controls ( P < 0.05). In a separate control group ( n = 6), even high-intensity static handgrip was not accompanied by sustained elevation of SSNA during PHG-CA. 31P-nuclear magnetic resonance spectroscopy during RHG demonstrated significant muscle acidosis and accumulation of inorganic phosphate in CHF patients ( n = 7) but not in controls ( n = 9). We conclude that in CHF patients rhythmic forearm exercise leads to premature fatigue and accumulation of muscle metabolites. The prominent PHG-CA response of MSNA and SSNA in CHF patients suggests activation of the muscle metaboreflex. Because, in contrast to controls, in CHF patients both MSNA and SSNA appear to be under muscle metaboreflex control, the mechanisms and distribution of sympathetic outflow during exercise appear to be different from normal.

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