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

2001 ◽  
Vol 281 (3) ◽  
pp. H1312-H1318 ◽  
Author(s):  
C. F. Notarius ◽  
D. J. Atchison ◽  
G. A. Rongen ◽  
J. S. Floras

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.

2001 ◽  
Vol 280 (3) ◽  
pp. H969-H976 ◽  
Author(s):  
Catherine F. Notarius ◽  
Deborah J. Atchison ◽  
John S. Floras

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.


2004 ◽  
Vol 10 (5) ◽  
pp. S167
Author(s):  
Hisayoshi Murai ◽  
Takata Shigeo ◽  
Furushou Hiroshi ◽  
Maruyama Micchirou ◽  
Takamura Masayuki ◽  
...  

2009 ◽  
Vol 587 (11) ◽  
pp. 2613-2622 ◽  
Author(s):  
Hisayoshi Murai ◽  
Masayuki Takamura ◽  
Michirou Maruyama ◽  
Manabu Nakano ◽  
Tatsunori Ikeda ◽  
...  

2002 ◽  
Vol 103 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Daisaku MICHIKAMI ◽  
Atsunori KAMIYA ◽  
Qi FU ◽  
Yuki NIIMI ◽  
Satoshi IWASE ◽  
...  

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.


1993 ◽  
Vol 75 (1) ◽  
pp. 228-232 ◽  
Author(s):  
C. A. Ray ◽  
A. L. Mark

Recent studies have shown a lack of an increase in muscle sympathetic nerve activity (MSNA) during leg exercise. Experiments using isometric knee extension (IKE) have shown a biphasic response in MSNA with a decrease during the 1st min and a return of MSNA to control levels during the 2nd min of IKE. Moreover, MSNA was not augmented during postexercise muscle ischemia (PEMI) of the exercising leg, suggesting that the muscle metaboreflex may have not been engaged in these experiments. The purpose of the present study was 1) to examine MSNA during IKE performed to fatigue to determine whether MSNA could be increased with leg exercise and 2) to determine whether increases in MSNA during fatiguing IKE were associated with an augmented MSNA response during PEMI. IKE was initially performed to fatigue at 30% of maximal voluntary contraction in the sitting position (n = 7; trial 1). IKE elicited a marked increase in mean arterial pressure and heart rate (P < 0.01). Total MSNA (burst frequency x mean burst amplitude; units) in the contralateral leg increased 96 +/- 40% (P < 0.01) above control levels during the final 30 s of IKE (207 +/- 23 s). Subjects (n = 8) then performed IKE to fatigue followed by PEMI (trial 2). MSNA in the contralateral leg increased 107 +/- 50% (P < 0.01) above control levels during the final 30 s of IKE (169 +/- 12 s) and remained significantly elevated during PEMI (83 +/- 40% above control), indicating that the muscle metaboreflex was engaged during fatiguing IKE.(ABSTRACT TRUNCATED AT 250 WORDS)


2015 ◽  
Vol 309 (7) ◽  
pp. H1218-H1224 ◽  
Author(s):  
Fatima El-Hamad ◽  
Elisabeth Lambert ◽  
Derek Abbott ◽  
Mathias Baumert

Beat-to-beat variability of the QT interval (QTV) is sought to provide an indirect noninvasive measure of sympathetic nerve activity, but a formal quantification of this relationship has not been provided. In this study we used power contribution analysis to study the relationship between QTV and muscle sympathetic nerve activity (MSNA). ECG and MSNA were recorded in 10 healthy subjects in the supine position and after 40° head-up tilt. Power spectrum analysis was performed using a linear autoregressive model with two external inputs: heart period (RR interval) variability (RRV) and MSNA. Total and low-frequency power of QTV was decomposed into contributions by RRV, MSNA, and sources independent of RRV and MSNA. Results show that the percentage of MSNA power contribution to QT is very small and does not change with tilt. RRV power contribution to QT power is notable and decreases with tilt, while the greatest percentage of QTV is independent of RRV and MSNA in the supine position and after 40° head-up tilt. In conclusion, beat-to-beat QTV in normal subjects does not appear to be significantly affected by the rhythmic modulations in MSNA following low to moderate orthostatic stimulation. Therefore, MSNA oscillations may not represent a useful surrogate for cardiac sympathetic nerve activity at moderate levels of activation, or, alternatively, sympathetic influences on QTV are complex and not quantifiable with linear shift-invariant autoregressive models.


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