β-Adrenergic blockade enhances coronary vasoconstrictor response to forehead cooling

Muller, Matthew D.; Gao, Zhaohui; Patel, Hiren; Heffernan, Matthew J.; Leuenberger, Urs A.; Sinoway, Lawrence I.

doi:10.1152/ajpheart.00787.2013

Cited by 13 publications

(18 citation statements)

References 73 publications

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“…Alternatively, older men may have augmented ␣-adrenergic coronary vasoconstrictor responses during exercise compared with young men, which would dampen coronary vasodilation. However, we recently showed that coronary vasoconstriction to noxious forehead cooling was comparable between young and older adults (45). Whether ␣-adrenergic coronary vasoconstriction is enhanced in older men during exercise is unknown.…”

Section: Discussionmentioning

confidence: 96%

“…Isoproterenol is a nonselective ␤-AR agonist with a short half-life (Ͻ2 min) that has been previously used by our laboratory (44,45) and others (5,42,49) to challenge the extent of ␤-AR blockade with propranolol. In the current study, intravenous propranolol completely blocked the tachycardia response to the peak dose of intravenous isoproterenol, indicating a full ␤-AR blockade.…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were instrumented with a three-lead EKG (Cardiocap/5; GE Healthcare) to monitor heart rate (HR), a finger BP cuff (Finometer, FMS), a pneumotrace to monitor respiratory movement, and an intravenous catheter in each arm. Before infusions and exercise, resting BPs were obtained in triplicate by automated oscillometry of the left brachial artery (Philips Sure Signs VS3) after 15 min of quiet rest and were used to verify the Finometer values as previously described (45). All of the variables listed above were collected at 200 Hz by PowerLab (ADInstruments).…”

Section: Ethical Approvalmentioning

confidence: 99%

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β-Adrenergic receptor blockade impairs coronary exercise hyperemia in young men but not older men

Ross

Gao

Pollock

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Patients with coronary artery disease have attenuated coronary vasodilator responses to physiological stress, which is partially attributed to a β-adrenergic receptor (β-AR)-mediated mechanisms. Whether β-ARs contribute to impaired coronary vasodilation seen with healthy aging is unknown. The purpose of this study was to investigate the role of β-ARs in coronary exercise hyperemia in healthy humans. Six young men (26 ± 1 yr) and seven older men (67 ± 4 yr) performed isometric handgrip exercise at 30% maximal voluntary contraction for 2 min after receiving intravenous propranolol, a β-AR antagonist, and no treatment. Isoproterenol, a β-AR agonist, was infused to confirm the β-AR blockade. Blood pressure and heart rate were monitored continuously, and coronary blood flow velocity (CBV, left anterior descending artery) was measured by transthoracic Doppler echocardiography. Older men had an attenuated ΔCBV to isometric exercise (3.8 ± 1.3 vs. 9.7 ± 2.1 cm/s, P = 0.02) compared with young men. Propranolol decreased the ΔCBV at peak handgrip exercise in young men (9.7 ± 2.1 vs. 2.7 ± 0.9 cm/s, P = 0.008). However, propranolol had no effect on ΔCBV in older men (3.8 ± 1.3 vs. 4.2 ± 1.9 cm/s, P = 0.9). Older men also had attenuated coronary hyperemia to low-dose isoproterenol. These data indicate that β-AR control of coronary blood flow is impaired in healthy older men.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Ethical Approvalmentioning

confidence: 99%

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β-Adrenergic receptor blockade impairs coronary exercise hyperemia in young men but not older men

Ross

Gao

Pollock

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…Our primary outcome variable was the ΔCBV to ΔRPP ratio from baseline to exercise, which was calculated as ΔCBV/ΔRPP × 1000. This ratio has been used previously to quantify coronary hyperemia normalized to cardiac metabolism; higher numbers indicate greater myocardial O 2 supply relative to demand [30–33]. Statistical analysis was performed using SPSS 22.…”

Section: Methodsmentioning

confidence: 99%

Coronary Exercise Hyperemia Is Impaired in Patients with Peripheral Arterial Disease

Ross

Gao

Luck

et al. 2017

Annals of Vascular Surgery

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STRUCTURED ABSTRACT Background Peripheral arterial disease (PAD) is an atherosclerotic vascular disease that affects over 200 million worldwide. The hallmark of PAD is ischemic leg pain and this condition is also associated with an augmented blood pressure response to exercise, impaired vascular function, and high risk of myocardial infarction and cardiovascular mortality. In this study, we tested the hypothesis that coronary exercise hyperemia is impaired in PAD. Methods Twelve patients with PAD and no overt coronary disease (65 ± 2 yr, 7 men) and 15 healthy control subjects (64 ± 2 yr, 9 men) performed supine plantar flexion exercise (30 contractions/min, increasing workload). A subset of subjects (N = 7 PAD, N = 8 healthy) also performed isometric handgrip exercise (40% maximum voluntary contraction to fatigue). Coronary blood velocity in the left anterior descending artery was measured by transthoracic Doppler echocardiography; blood pressure and heart rate were monitored continuously. Results Coronary blood velocity responses to 4 minutes of plantar flexion exercise (PAD: Δ 2.4 ± 1.2, healthy: Δ 6.0 ± 1.6 cm/s, P = 0.039) and to isometric handgrip exercise (PAD: Δ 8.3 ± 4.2, healthy: Δ 16.9 ± 3.6, P = 0.033) were attenuated in PAD patients. Conclusions These data indicate that coronary exercise hyperemia is impaired in PAD, which may predispose these patients to myocardial ischemia.

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“…Prior to each stressor, three resting BPs were obtained by automated oscillometry of the right brachial artery (Philips Sure Signs VS3) after 15 min of quiet rest and these were used to verify the Finometer values as previously described (Muller et al. ). All beat‐by‐beat variables were collected at 200 Hz by PowerLab (ADInstruments).…”

Section: Methodsmentioning

confidence: 99%

Effect of adrenergic agonists on coronary blood flow: a laboratory study in healthy volunteers

et al. 2016

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Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α‐adrenergic receptors and β‐adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone. The purpose of this laboratory study was to noninvasively quantify coronary responses to adrenergic receptor stimulation in humans. Fourteen healthy volunteers (11 men and 3 women) performed isometric handgrip exercise to fatigue followed by intravenous infusion of isoproterenol. A subset of individuals also received infusions of phenylephrine (n = 6), terbutaline (n = 10), and epinephrine (n = 4); all dosages were based on fat‐free mass and were infused slowly to achieve steady‐state. The left anterior descending coronary artery was visualized using Doppler echocardiography. Beat‐by‐beat heart rate (HR), blood pressure (BP), peak diastolic coronary velocity (CBVpeak), and coronary velocity time integral were calculated. Data are presented as M ± SD. Isometric handgrip elicited significant increases in BP, HR, and CBVpeak (from 23.3 ± 5.3 to 34.5 ± 9.9 cm/sec). Isoproterenol raised HR and CBVpeak (from 22.6 ± 4.8 to 43.9 ± 12.4 cm/sec). Terbutaline and epinephrine evoked coronary hyperemia whereas phenylephrine did not significantly alter CBVpeak. Different indices of coronary hyperemia (changes in CBVpeak and velocity time integral) were significantly correlated (R = 0.803). The current data indicate that coronary hyperemia occurs in healthy humans in response to isometric handgrip exercise and low‐dose, steady‐state infusions of isoproterenol, terbutaline, and epinephrine. The contribution of β1 versus β2 receptors to coronary hyperemia remains to be determined. In this echocardiographic study, we demonstrate that coronary blood flow increases when β‐adrenergic receptors are stimulated (i.e., during exercise and different intravenous infusions). Our infusion paradigms and beat‐by‐beat imaging methodologies can be used in future studies to evaluate age‐, sex‐, and disease‐ differences in adrenergic control of coronary blood flow.

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β-Adrenergic blockade enhances coronary vasoconstrictor response to forehead cooling

Cited by 13 publications

References 73 publications

β-Adrenergic receptor blockade impairs coronary exercise hyperemia in young men but not older men

β-Adrenergic receptor blockade impairs coronary exercise hyperemia in young men but not older men

Coronary Exercise Hyperemia Is Impaired in Patients with Peripheral Arterial Disease

Effect of adrenergic agonists on coronary blood flow: a laboratory study in healthy volunteers

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