Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function

Endothelial cell release of nitric oxide (NO) is a defining characteristic of nondiseased arteries, and abnormal endothelial NO release is both a marker of early atherosclerosis and a predictor of its progression and future events. Healthy coronaries respond to endothelial-dependent stressors with vasodilatation and increased coronary blood flow (CBF), but those with endothelial dysfunction respond with paradoxical vasoconstriction and reduced CBF. Recently, coronary MRI and isometric handgrip exercise (IHE) were reported to noninvasively quantify coronary endothelial function (CEF). However, it is not known whether the coronary response to IHE is actually mediated by NO and/or whether it is reproducible over weeks. To determine the contribution of NO, we studied the coronary response to IHE before and during infusion of NG-monomethyl-l-arginine (l-NMMA, 0.3 mg·kg−1·min−1), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies ∼8 wk apart in healthy subjects and patients with coronary artery disease (CAD). Changes from rest to IHE in coronary cross-sectional area (%CSA) and diastolic CBF (%CBF) were quantified. l-NMMA completely blocked normal coronary vasodilation during IHE [%CSA, 12.9 ± 2.5 (mean ± SE, placebo) vs. −0.3 ± 1.6% (l-NMMA); P < 0.001] and significantly blunted the increase in flow [%CBF, 47.7 ± 6.4 (placebo) vs. 10.6 ± 4.6% (l-NMMA); P < 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA ( P < 0.0001) and CBF ( P < 0.01). In conclusion, the normal human coronary vasoactive response to IHE is primarily mediated by NO. This noninvasive, reproducible MRI-IHE exam of NO-mediated CEF promises to be useful for studying CAD pathogenesis in low-risk populations and for evaluating translational strategies designed to alter CAD in patients.

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Non-invasive assessment of coronary endothelial function in children and adolescents with type 1 diabetes mellitus using isometric handgrip exercise—MRI: A feasibility study

PLoS ONE ◽

10.1371/journal.pone.0228569 ◽

2020 ◽

Vol 15 (2) ◽

pp. e0228569 ◽

Cited By ~ 1

Author(s):

Gaëtan Zwingli ◽

Jérôme Yerly ◽

Yvan Mivelaz ◽

Sophie Stoppa-Vaucher ◽

Andrew A. Dwyer ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Endothelial Function ◽

Type 1 Diabetes Mellitus ◽

Children And Adolescents ◽

Handgrip Exercise ◽

Isometric Handgrip ◽

Non Invasive ◽

Isometric Handgrip Exercise

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Abstract 13292: A Novel Reproducible Noninvasive Imaging Approach to Quantify Nitric Oxide-mediated Coronary Endothelial Function in Humans

Circulation ◽

10.1161/circ.130.suppl_2.13292 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Micaela Iantorno ◽

Allison G Hays ◽

Sahar Soleimanifard ◽

Angela Steinberg ◽

Michael Schar ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Endothelial Function ◽

Coronary Blood Flow ◽

Repeated Measures ◽

Healthy Subjects ◽

Cine Mri ◽

Isometric Handgrip ◽

Coronary Endothelial Function ◽

The Impact

Endothelial release of nitric oxide (NO) is a defining characteristic of non-diseased vascular tissue. Healthy coronary arteries respond to endothelial-dependent stressors with vasodilatation but those with endothelial dysfunction respond with paradoxical vasoconstriction. The combination of new non-invasive 3T coronary MRI methods and isometric handgrip exercise (IHE), has been suggested as a means to noninvasively quantify coronary endothelial function (CEF). However, IHE may trigger neural, neuro-hormonal and other vasoreactive responses; thus, it is unknown whether the IHE-induced coronary response is, in fact, primarily mediated by NO. Furthermore, it is not known whether the MRI-IHE test is reproducible over time.To test the hypothesis that the IHE-induced coronary response is NO-mediated, we performed MRI-IHE studies before and during the infusion of monomethyl-L-arginine (L-NMMA, 0.3mg/kg/min), a NO synthase inhibitor in 8 healthy subjects. To study reproducibility we performed 2 MRI-IHE studies ~8 weeks apart in 8 coronary artery disease (CAD) patients and 9 healthy subjects. Changes from rest to IHE in coronary cross-sectional area (%CSA) and coronary blood flow (%CBF) were measured with cine MRI. L-NMMA completely blocked coronary vasodilation during IHE (%CSA change 15.4%±2.8% with placebo vs -1.6%±1.3% with L-NMMA; p<0.0001) and the normal increase in coronary blood flow (%CBF change 50.2%±6.7% with placebo vs -2.1%±6.7% with L-NMMA; p< 0.0001). Moreover, there was a strong correlation between repeated measures for %CSA change with IHE at the two exams (R=0.91, p<0.0001) and %CBF change with IHE (R=0.80; p<0.001). Bland-Altman analysis and intra-class correlation coefficients for %CSA and %CBF change with IHE (0.90 and 0.80, respectively) indicated good agreement and little variability between repeated measures. In summary the coronary response to IHE is largely mediated by endothelial-derived NO and is reproducible over several weeks. Thus MRI-IHE is a noninvasive, reproducible tool to assess CEF, arguably the first to noninvasively measure macro- and micro-vascular NO-mediated coronary responses. This noninvasive tool may be useful in future studies of the impact of interventions on CAD pathogenesis.

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Isometric Handgrip Exercise Training Improves Spirometric Parameters and Pulmonary Capacity

Pathophysiology ◽

10.3390/pathophysiology28030022 ◽

2021 ◽

Vol 28 (3) ◽

pp. 328-338

Author(s):

Ogbutor Udoji Godsday ◽

Nwangwa Eze Kingsley ◽

Nwogueze Bartholomew Chukwuebuka ◽

Chukwuemeka Ephraim ◽

Ezunu Emmanuel ◽

...

Keyword(s):

Pulmonary Function ◽

Isometric Exercise ◽

Handgrip Exercise ◽

Isometric Handgrip ◽

Post Exercise ◽

Significant Difference ◽

Isometric Handgrip Exercise ◽

Group 3 ◽

Group 2 ◽

Group 1

Decline in normal physiological pulmonary function has been attributed to premorbid conditions such as prehypertension. Research evidence suggests that physical activity reduces age-related decline in pulmonary function and improves the efficiency of the lungs in prehypertensive patients. However, there is a scarcity of data evidence relating to isometric exercise and pulmonary function. Furthermore, the interrelationship between the intensity and duration of isometric exercise and pulmonary function in these patients is still uncertain. Therefore, this study was undertaken to investigate the effect of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. To determine the effectiveness of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. A quasi experiment using a pre- and post-exercise method was carried out in two out-patients hospital settings. The sample comprised 192 sedentary pre-hypertensive subjects, aged between 30–50 years, that were randomly distributed into three groups of 64 participants each. The subjects performed, for 24 consecutive days, an isometric handgrip exercise at 30% Maximum Voluntary Contraction (M.V.C.). At the end of the 24 days, group one (GP1) discontinued, while group two (GP2) continued the exercise protocol for another 24 consecutive days and group three (GP3) continued with the exercise protocol for another 24 consecutive days but at 50% M.V.C. Determinants of lung function (outcomes) were Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), FEV1/FVC Ratio and Peak Expiratory Flow Rate (PEFR). The study shows that there was no statistically significant difference in the pre- and post-exercise outcomes for FEV1, FVC, FEV1/FVC Ratio and PEFR after 24 days for group 1. In group 2, there was a statistically significant difference in the FVC [(mean = 0.12 ± 0.12), (p = 0.002)], FEV1 [(mean = 0.15 ± 0.17), (p = 0.003)] and PEF [(mean = 0.85 ± 0.35), (p = 0.001)] after 48 days. In group 3, there was a statistically significant difference (p = 0.001) in all the outcomes assessed after 48 days. There was a between groups difference in favour of group 2 compared with group 1 for outcomes of FEV1 [(mean = 0.142 ± 0.68), (p = 0.005)] and PEF [(mean = 0.83 ± 0.19), (p = 0.0031)]. There was statistically significant difference in favour of group 3 compared to group 2, by increasing the exercise intensity from 30% to 50% M.V.C., for outcomes of FVC [mean change = 0.10 ± 0.052), (p = 0.005)], FEV1/FVC [mean change = 3.18 ± 0.75), (p = 0.017)] and PEF [(mean change = 0.86 ± 0.35), (p = 0.001)] after 48 days. Isometric handgrip exercise (after 48 days at 30% to 50% M.V.C.) improves outcomes of pulmonary function capacity in adults with prehypertension. Meanwhile, duration and/or increase in intensity of the isometric effort significantly contributed to the affects attained.

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Association of changes of pulse wave velocity and augmentation index after isometric handgrip exercise with coronary lesion extent and revascularization

Clinical Hypertension ◽

10.1186/s40885-021-00163-5 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Seong Taeg Kim ◽

Yeekyoung Ko ◽

Jong-Wook Beom ◽

Ki Yung Boo ◽

Jae-Geun Lee ◽

...

Keyword(s):

Arterial Stiffness ◽

Pulse Wave Velocity ◽

Iliac Artery ◽

Pulse Wave ◽

Augmentation Index ◽

Coronary Revascularization ◽

External Iliac Artery ◽

Handgrip Exercise ◽

Isometric Handgrip ◽

Isometric Handgrip Exercise

Abstract Background Arterial stiffness is associated with myocardial ischemia and incident coronary artery disease (CAD), and indexes of arterial stiffness are usually increased in patients with CAD. However, these indexes are often increased in elderly without CAD. Arterial stiffness in patients with CAD may become more evident after isometric handgrip exercise which increases systolic pressure and ventricular afterload. We investigated the association of the change of stiffness indexes after isometric handgrip exercise with the lesion extent of CAD and the necessity for coronary revascularization. Methods Patients who were scheduled a routine coronary angiography via a femoral artery were enrolled. Arterial waveforms were traced at aortic root and external iliac artery using coronary catheters at baseline and 3 min after handgrip exercise. Augmentation index (AIx) was measured on the recorded aortic pressure waveform, and pulse wave velocity (PWV) was calculated using the ECG-gated time difference of the upstroke of arterial waveforms and distance between aortic root and external iliac artery. Results Total 37 patients were evaluated. Both PWV and AIx increased after handgrip exercise. ΔPWV was significantly correlated with ΔAIx (r = 0.344, P = 0.037). Patients were divided into higher and lower ΔPWV or ΔAIx groups based on the median values of 0.4 m/sec and 3.3%, respectively. Patients with higher PWV had more 2- or 3-vessel CAD (69% vs. 27%, P = 0.034), and underwent percutaneous coronary intervention (PCI) more frequently (84% vs. 50%, P = 0.038), but higher ΔAIx was not associated with either the lesion extent or PCI. Area under curve (AUC) of ΔPWV in association with PCI by C-statistics was 0.70 (95% confidence interval [CI] 0.51–0.88; P = 0.056). In multiple logistic regression analysis, ΔPWV was significantly associated with PCI (odds ratio 7.78; 95% CI 1.26–48.02; P = 0.027). Conclusions Higher ΔPWV after isometric handgrip exercise was associated with the lesion extent of CAD and the necessity for coronary revascularization, but higher ΔAIx was not.

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Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide

Clinical Science ◽

10.1042/cs1010629 ◽

2001 ◽

Vol 101 (6) ◽

pp. 629-635 ◽

Cited By ~ 180

Author(s):

Sagar N. DOSHI ◽

Katerina K. NAKA ◽

Nicola PAYNE ◽

Christopher J.H. JONES ◽

Moira ASHTON ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Function ◽

Brachial Artery ◽

Peak Flow ◽

Ultrasound Probe ◽

Upper Arm ◽

Flow Mediated Dilatation ◽

Synthase Inhibitor ◽

Increased Blood Flow ◽

Similar Peak

Flow-mediated dilatation (FMD) of the brachial artery assessed by high-resolution ultrasound is widely used to measure endothelial function. However, the technique is not standardized, with different groups using occlusion of either the wrist or the upper arm to induce increased blood flow. The validity of the test as a marker of endothelial function rests on the assumption that the dilatation observed is endothelium-dependent and mediated by nitric oxide (NO). We sought to compare the NO component of brachial artery dilatation observed following wrist or upper arm occlusion. Dilatation was assessed before and during intra-arterial infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) following occlusion of (i) the wrist (distal to ultrasound probe) and (ii) the upper arm (proximal to ultrasound probe) for 5min in ten healthy males. Dilatation was significantly greater after upper arm occlusion (upper arm, 11.62±3.17%; wrist, 7.25±2.49%; P = 0.003). During l-NMMA infusion, dilatation after wrist occlusion was abolished (from 7.25±2.49% to 0.16±2.24%; P < 0.001), whereas dilatation after upper arm occlusion was only partially attenuated (from 11.62±3.17% to 7.51±2.34%; P = 0.006). The peak flow stimulus was similar after wrist and upper arm occlusion. We conclude that dilatation following upper arm occlusion is greater than that observed after wrist occlusion, despite a similar peak flow stimulus. l-NMMA infusion revealed that FMD following wrist occlusion is mediated exclusively by NO, while dilatation following upper arm occlusion comprises a substantial component not mediated by NO, most probably related to tissue ischaemia around the brachial artery. FMD following wrist occlusion may be a more valid marker of endothelial function than dilatation following upper arm occlusion.

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Developmental Changes in Hemodynamic Responses and Cardiovagal Modulation during Isometric Handgrip Exercise

International Journal of Pediatrics ◽

10.1155/2010/153780 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Styliani Goulopoulou ◽

Bo Fernhall ◽

Jill A. Kanaley

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Isometric Contraction ◽

Pressor Response ◽

Reflex Response ◽

Group Differences ◽

Handgrip Exercise ◽

Isometric Handgrip ◽

Isometric Handgrip Exercise ◽

Pressor Reflex

The purpose of this study was to examine differences in pressor response and cardiovagal modulation during isometric handgrip exercise (IHG) between children and adults. Beat-to-beat heart rate (HR) and blood pressure were measured in 23 prepubertal children and 23 adults at baseline and during IHG. Cardiovagal modulation was quantified by analysis of HR variability. Mean arterial pressure responses to IHG were greater in adults compared to children (P<.05) whereas there were no group differences in HR responses (P>.05). Children had a greater reduction in cardiovagal modulation in response to IHG compared to adults (P<.05). Changes in mean arterial pressure during IHG were correlated with baseline cardiovagal modulation and force produced during isometric contraction (P<.05). In conclusion, differences in pressor reflex response between children and adults cannot be solely explained by differences in autonomic modulation and appear to be associated with factors contributing to the force produced during isometric contraction.

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Effect of isometric handgrip exercise on intraocular pressure among healthy adult males

Comparative Exercise Physiology ◽

10.3920/cep200048 ◽

2020 ◽

pp. 1-6

Author(s):

S. Ezhilnila ◽

S. Brinda ◽

A. Meena ◽

P.J. Samuel

Keyword(s):

Intraocular Pressure ◽

Healthy Adult ◽

Lifestyle Modification ◽

Maximum Voluntary Contraction ◽

South Indian Population ◽

Adult Males ◽

Handgrip Exercise ◽

Isometric Handgrip ◽

South Indian ◽

Isometric Handgrip Exercise

Glaucoma is the main cause for irreversible blindness in India. The main determinant of glaucoma is raised intraocular pressure (IOP) which is influenced by many factors. One of the main factors is physical exercise. Objective of this study is to exhibit the effect of isometric handgrip exercise using Smedley’s handgrip dynamometer on IOP among young adult males in the south Indian population. In this quasi experimental study, 150 young healthy adult male subjects with ages between 15 to 40 years were selected on the basis of fulfilling our inclusion and exclusion criteria with the help of a questionnaire. Baseline IOP and maximum voluntary contraction (MVC) of the subjects were measured using non-contact tonometer and Smedley’s Handgrip Dynamometer, respectively. The subjects were instructed to hold the handgrip dynamometer with 20% of MVC in sustained manner for minimum 2 min or until fatigue sets in. IOP were measured on both eyes immediately and 15 min following exercise and IOP variation was analysed using paired t-test. A small but significant decrease in IOP was noted immediately as well as 15 min following exercise. Average fall in right eye was 1.75 mm Hg immediately and 2.14 mm Hg 15 min following exercise (P<0.01). The average fall in the left eye was 1.62 mm Hg immediately and 1.91 mm Hg after 15 min (P<0.01). Isometric handgrip exercise of the single upper limb showed significant reduction of IOP on both eyes following exercise and the decrease was much higher 15 min after exercise. This result can be extrapolated and clinically applied for glaucoma prevention and supplemented as lifestyle modification during glaucoma treatment.

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