Forearm blood flow responses to handgripping after local neuromuscular blockade

1998 ◽  
Vol 84 (2) ◽  
pp. 754-758 ◽  
Author(s):  
Christopher K. Dyke ◽  
Niki M. Dietz ◽  
Robert L. Lennon ◽  
David O. Warner ◽  
Michael J. Joyner
Keyword(s):  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Neuromuscular Blockade ◽  
Drug Administration ◽  
Forearm Blood Flow ◽  
Maximum Voluntary Contraction ◽  
Voluntary Contraction ◽  
Neuromuscular Blocking ◽  
Motor Nerves

Dyke, Christopher K., Niki M. Dietz, Robert L. Lennon, David O. Warner, and Michael J. Joyner. Forearm blood flow responses to handgripping after local neuromuscular blockade. J. Appl. Physiol. 84(2): 754–758, 1998.—To test the hypothesis that acetylcholine “spillover” from motor nerves contributes significantly to skeletal muscle vasodilation during exercise, we measured the forearm blood flow responses during attempted handgripping after local paralysis of the forearm with the neuromuscular-blocking drug pipecuronium. This compound blocks postsynaptic nicotinic receptors but has no impact on acetylcholine release from motor nerves. The drug was administered selectively to one forearm by using regional intravenous drug administration techniques in five subjects. Pipecuronium reduced maximum forearm grip strength from 40.0 ± 3.2 kg before treatment to 0.0 kg after treatment. By contrast, drug administration had no effect on maximum voluntary contraction in the untreated forearm (41.3 ± 3.3 vs. 41.4 ± 2.7 kg). During 2 min of attempted maximal contraction of the paralyzed forearm, the forearm blood flow increased from only 3.4 ± 0.8 to 4.8 ± 1.2 ml ⋅ 100 ml−1 ⋅ min−1( P < 0.05). Heart rate increased from 63 ± 3 to 73 ± 8 beats/min ( P > 0.05) during attempted contraction, and only three of five subjects showed obvious increases in heart rate. Mean arterial pressure increased significantly ( P < 0.05) from 102 ± 6 to 109 ± 9 mmHg during attempted contractions. When these increases in flow are considered in the context of the marked (10-fold or greater) increases in flow seen in contracting forearm skeletal muscle, it appears that acetylcholine spillover from motor nerves has, at most, a minimal impact on the hyperemic responses to contraction in humans.

scholarly journals Effect of vitamin C on hyperoxia-induced vasoconstriction in exercising skeletal muscle

2014 ◽  
Vol 117 (10) ◽  
pp. 1207-1211 ◽  
Author(s):  
Sushant M. Ranadive ◽  
Michael J. Joyner ◽  
Branton G. Walker ◽  
Jennifer L. Taylor ◽  
Darren P. Casey
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Vitamin C ◽  
Muscle Blood Flow ◽  
Maximum Voluntary Contraction ◽  
Voluntary Contraction ◽  
Ros Generation ◽  
Forearm Vascular Conductance ◽  
Forearm Exercise ◽  
Induced Changes

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.

scholarly journals Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

2013 ◽  
Vol 305 (1) ◽  
pp. H29-H40 ◽  
Author(s):  
Anne R. Crecelius ◽  
Brett S. Kirby ◽  
Gary J. Luckasen ◽  
Dennis G. Larson ◽  
Frank A. Dinenno
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Signaling Pathways ◽  
Muscle Blood Flow ◽  
Maximum Voluntary Contraction ◽  
Area Under The Curve ◽  
Voluntary Contraction ◽  
Impact Peak ◽  
Inwardly Rectifying

A monophasic increase in skeletal muscle blood flow is observed after a brief single forearm contraction in humans, yet the underlying vascular signaling pathways remain largely undetermined. Evidence from experimental animals indicates an obligatory role of vasodilation via K+-mediated smooth muscle hyperpolarization, and human data suggest little to no independent role for nitric oxide (NO) or vasodilating prostaglandins (PGs). We tested the hypothesis that K+-mediated vascular hyperpolarization underlies the rapid vasodilation in humans and that combined inhibition of NO and PGs would have a minimal effect on this response. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10 s before and for 30 s after a single 1-s dynamic forearm contraction at 10%, 20%, and 40% maximum voluntary contraction in 16 young adults. To inhibit K+-mediated vasodilation, BaCl2 and ouabain were infused intra-arterially to inhibit inwardly rectifying K+ channels and Na+-K+-ATPase, respectively. Combined enzymatic inhibition of NO and PG synthesis occurred via NG-monomethyl-l-arginine (l-NMMA; NO synthase) and ketorolac (cyclooxygenase), respectively. In protocol 1 ( n = 8), BaCl2 + ouabain reduced peak vasodilation (range: 30–45%, P < 0.05) and total postcontraction vasodilation (area under the curve, ∼55–75% from control) at all intensities. Contrary to our hypothesis, l-NMMA + ketorolac had a further impact (peak: ∼60% and area under the curve: ∼80% from control). In protocol 2 ( n = 8), the order of inhibitors was reversed, and the findings were remarkably similar. We conclude that K+-mediated hyperpolarization and NO and PGs, in combination, significantly contribute to contraction-induced rapid vasodilation and that inhibition of these signaling pathways nearly abolishes this phenomenon in humans.

Forearm blood flow follows work rate during submaximal dynamic forearm exercise independent of sex

2007 ◽  
Vol 103 (6) ◽  
pp. 1950-1957 ◽  
Author(s):  
Joaquin U. Gonzales ◽  
Benjamin C. Thompson ◽  
John R. Thistlethwaite ◽  
Allison J. Harper ◽  
Barry W. Scheuermann
Keyword(s):  
Blood Flow ◽  
Muscle Strength ◽  
Forearm Blood Flow ◽  
Handgrip Strength ◽  
Maximum Voluntary Contraction ◽  
Voluntary Contraction ◽  
Work Rate ◽  
Metabolic Demand ◽  
Task Failure ◽  
Forearm Exercise

To test the hypothesis that sex influences forearm blood flow (FBF) during exercise, 15 women and 16 men of similar age [women 24.3 ± 4.0 (SD) vs. men 24.9 ± 4.5 yr] but different forearm muscle strength (women 290.7 ± 44.4 vs. men 509.6 ± 97.8 N; P < 0.05) performed dynamic handgrip exercise as the same absolute workload was increased in a ramp function (0.25 W/min). Task failure was defined as the inability to maintain contraction rate. Blood pressure and FBF were measured on separate arms during exercise by auscultation and Doppler ultrasound, respectively. Muscle strength was positively correlated with endurance time ( r = 0.72, P < 0.01) such that women had a shorter time to task failure than men (450.5 ± 113.0 vs. 831.3 ± 272.9 s; P < 0.05). However, the percentage of maximal handgrip strength achieved at task failure was similar between sexes (14% maximum voluntary contraction). FBF was similar between women and men throughout exercise and at task failure (women 13.6 ± 5.3 vs. men 14.5 ± 4.9 ml·min−1·100 ml−1). Mean arterial pressure was lower in women at rest and during exercise; thus calculated forearm vascular conductance (FVC) was higher in women during exercise but similar between sexes at task failure (women 0.13 ± 0.05 vs. men 0.11 ± 0.04 ml·min−1·100 ml−1·mmHg−1). In conclusion, the similar FBF during exercise was achieved by a higher FVC in the presence of a lower MAP in women than men. Still, FBF remained coupled to work rate (and presumably metabolic demand) during exercise irrespective of sex.

Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans

1996 ◽  
Vol 81 (4) ◽  
pp. 1516-1521 ◽  
Author(s):  
J. K. Shoemaker ◽  
H. L. Naylor ◽  
Z. I. Pozeg ◽  
R. L. Hughson
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Forearm Blood Flow ◽  
Voluntary Contraction ◽  
Double Blind ◽  
Rate Of Increase ◽  
Forearm Exercise ◽  
Blind Manner ◽  
Exercise In Humans

Shoemaker, J. K., H. L. Naylor, Z. I. Pozeg, and R. L. Hughson. Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans. J. Appl. Physiol. 81(4): 1516–1521, 1996.—The time course and magnitude of increases in brachial artery mean blood velocity (MBV; pulsed Doppler), diameter ( D; echo Doppler), mean perfusion pressure (MPP; Finapres), shear rate (γ˙ = 8 ⋅ MBV/ D), and forearm blood flow (FBF = MBV ⋅ π r 2) were assessed to investigate the effect that prostaglandins (PGs) have on the hyperemic response on going from rest to rhythmic exercise in humans. While supine, eight healthy men performed 5 min of dynamic handgrip exercise by alternately raising and lowering a 4.4-kg weight (∼10% maximal voluntary contraction) with a work-to-rest cycle of 1:1 (s/s). When the exercise was performed with the arm positioned below the heart, the rate of increase in MBV and γ˙ was faster compared with the same exercise performed above the heart. Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) and placebo were administered orally for 2 days before two separate testing sessions in a double-blind manner. Resting heart rate was reduced in Ibu (52 ± 3 beats/min) compared with placebo (57 ± 3 beats/min) ( P < 0.05) without change to MPP. With placebo, D increased in both arm positions from ∼4.3 mm at rest to ∼4.5 mm at 5 min of exercise ( P < 0.05). This response was not altered with Ibu ( P > 0.05). Ibu did not alter the time course of MBV or forearm blood flow ( P > 0.05) in either arm position. The γ˙ was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 s of below the heart exercise ( P < 0.05). Because PG inhibition altered the time course ofγ˙ at the brachial artery, but not FBF, it was concluded that PGs are not essential in regulating the blood flow responses to dynamic exercise in humans.

scholarly journals Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine

2018 ◽  
Vol 129 (5) ◽  
pp. 970-988 ◽  
Author(s):  
John J. Savarese ◽  
Hiroshi Sunaga ◽  
Jeff D. McGilvra ◽  
Matthew R. Belmont ◽  
Matthew T. Murrell ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Neuromuscular Blockade ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Duration Of Action ◽  
Short Acting ◽  
Circulatory Effects

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Structure–activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. Methods Adduction of CW 1759-50 with l-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee–approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by l-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. Results The half-time of adduction of l-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of l-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. Conclusions CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by l-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.

scholarly journals Effects of acetylcholine and nitric oxide on forearm blood flow at rest and after a single muscle contraction

1998 ◽  
Vol 85 (6) ◽  
pp. 2249-2254 ◽  
Author(s):  
R. W. Brock ◽  
M. E. Tschakovsky ◽  
J. K. Shoemaker ◽  
J. R. Halliwill ◽  
M. J. Joyner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Muscle Contraction ◽  
Forearm Blood Flow ◽  
Mechanical Effect ◽  
Voluntary Contraction ◽  
Single Muscle ◽  
Cuff Inflation ◽  
S Period ◽  
Echo Doppler Ultrasound

We tested the hypothesis that ACh or nitric oxide (NO) might be involved in the vasodilation that accompanies a single contraction of the forearm. Eight adults (3 women and 5 men) completed single 1-s-duration contractions of the forearm to raise and lower a weight equivalent to ∼20% maximal voluntary contraction through a distance of 5 cm. In a second protocol, each subject had a cuff, placed completely about the forearm, inflated to 120 mmHg for a 1-s period, then released as a simulation of the mechanical effect of muscle contraction. Three conditions were studied, always in this order: 1) control, with intra-arterial infusion of saline; 2) after muscarinic blockade with atropine; and 3) after NO synthase inhibition with N G-monomethyl-l-arginine (l-NMMA) plus atropine. Forearm blood flow (FBF), measured by combined pulsed and echo Doppler ultrasound, was reduced at rest with l-NMMA-atropine compared with the other two conditions. After the single contraction, there were no effects of atropine, butl-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereasl-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation thatl-NMMA reduced FBF in response to both cuff inflation and a brief contraction indicates that NO from the vascular endothelium might modulate the basal level of vascular tone and the mechanical component of the hyperemia with exercise. It is unlikely that ACh and NO from the endothelium are involved in the dilator response to a single muscle contraction.

scholarly journals Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle

2018 ◽  
Vol 115 (3) ◽  
pp. 590-601 ◽  
Author(s):  
Dino Premilovac ◽  
Emily Attrill ◽  
Stephen Rattigan ◽  
Stephen M Richards ◽  
Jeonga Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Microvascular Blood Flow ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Skeletal Muscle Glucose Uptake

Abstract Aims Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin’s microvascular and metabolic actions in skeletal muscle. Methods and results Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinaemic euglycaemic clamp), or insulin (hyperinsulinaemic euglycaemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinaemic euglycaemic clamp) infusion. In all animals’ systemic metabolic effects, central haemodynamics, femoral artery blood flow, microvascular blood flow, and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate, and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinaemic euglycaemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin’s effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate, or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow, and this was accompanied by reduced skeletal muscle glucose uptake. Conclusions Acute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin’s microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.

Sympathetic modulation of blood flow and O2 uptake in rhythmically contracting human forearm muscles

1992 ◽  
Vol 263 (4) ◽  
pp. H1078-H1083 ◽  
Author(s):  
M. J. Joyner ◽  
L. A. Nauss ◽  
M. A. Warner ◽  
D. O. Warner
Keyword(s):  
Blood Flow ◽  
Body Position ◽  
Maximum Voluntary Contraction ◽  
Sympathetic Nerves ◽  
Work Load ◽  
Voluntary Contraction ◽  
Sympathetic Block ◽  
O2 Uptake ◽  
Fick Principle ◽  
Rhythmic Exercise

This study tested the effects of sympathetically mediated changes in blood flow to active muscles on muscle O2 uptake (VO2) in humans. Four minutes of graded (15-80% of maximum voluntary contraction, MVC) rhythmic handgrip exercise were performed. Forearm blood flow (FBF) (plethysmography) and deep vein O2 saturation were measured each minute. Forearm O2 uptake was calculated using the Fick principle. In protocol 1, exercise was performed while supine and again while upright to augment sympathetic outflow to the active muscles. Standing reduced FBF at rest from 3.6 to 2.2 ml.100 ml-1.min-1 (P < 0.05). During light exercise (15-40% MVC) FBF was unaffected by body position. Standing reduced FBF (P < 0.05) from 36.0 to 25.2 ml.100 ml-1.min-1 and forearm VO2 from 38.2 to 28.1 ml.kg-1.min-1 during the final work load. In protocol 2, exercise was performed while supine before and after local anesthetic block of the sympathetic nerves to the forearm. Sympathetic block increased FBF at rest from 3.1 to 8.9 ml.100 ml-1.min-1 (P < 0.05), and FBF was higher during all work loads At 70-80% of MVC sympathetic block increased FBF from 35.4 to 50.7 ml.100 ml-1.min-1 (P < 0.05), and forearm VO2 from 45.5 to 54.2 ml.kg-1.min-1 (P < 0.05). These results suggest that in humans sympathetic nerves modulate blood flow to active muscles during light and heavy rhythmic exercise and that this restraint of flow can limit O2 uptake in muscles performing heavy rhythmic exercise.

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