Matthew D. Muller

Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients

•  Peripheral arterial disease (PAD) is a common and debilitating condition linked with heightened risk of cardiovascular mortality. •  Dynamic exercise elicits augmented blood pressure responses in PAD that could put the patient at risk for adverse event but the underlying mechanisms are unknown. •  The exercise pressor reflex is comprised of group III and group IV muscle afferents that increase their discharge in response to mechanical and/or chemical stimulation. •  In this study, we demonstrate that mechanically sensitive muscle afferents cause augmented reflex elevations in blood pressure during dynamic plantar flexion exercise in PAD. These responses occur prior to claudication pain, are related to disease severity and can be partly reduced by acute antioxidant infusion.

Effect of cold air inhalation and isometric exercise on coronary blood flow and myocardial function in humans

The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O(2) saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O(2) demand, whereas CBV was used as an index of myocardial O(2) supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold + grip protocol caused a significantly greater increase in RPP compared with the grip protocol (P = 0.045), but the increase in CBV was significantly less (P = 0.039). However, myocardial function was not impaired during the cold + grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow.

Aging attenuates the coronary blood flow response to cold air breathing and isometric handgrip in healthy humans

The purpose of this echocardiography study was to measure peak coronary blood flow velocity (CBV(peak)) and left ventricular function (via tissue Doppler imaging) during separate and combined bouts of cold air inhalation (-14 ± 3°C) and isometric handgrip (30% maximum voluntary contraction). Thirteen young adults and thirteen older adults volunteered to participate in this study and underwent echocardiographic examination in the left lateral position. Cold air inhalation was 5 min in duration, and isometric handgrip (grip protocol) was 2 min in duration; a combined stimulus (cold + grip protocol) and a cold pressor test (hand in 1°C water) were also performed. Heart rate, blood pressure, O(2) saturation, and inspired air temperature were monitored on a beat-by-beat basis. The rate-pressure product (RPP) was used as an index of myocardial O(2) demand, and CBV(peak) was used as an index of myocardial O(2) supply. The RPP response to the grip protocol was significantly blunted in older subjects (Δ1,964 ± 396 beats·min(-1)·mmHg) compared with young subjects (Δ3,898 ± 452 beats·min(-1)·mmHg), and the change in CBV(peak) was also blunted (Δ6.3 ± 1.2 vs. 11.2 ± 2.0 cm/s). Paired t-tests showed that older subjects had a greater change in the RPP during the cold + grip protocol [Δ2,697 ± 391 beats·min(-1)·mmHg compared with the grip protocol alone (Δ2,115 ± 375 beats·min(-1)·mmHg)]. An accentuated RPP response to the cold + grip protocol (compared with the grip protocol alone) without a concomitant increase in CBV(peak) may suggest a dissociation between the O(2) supply and demand in the coronary circulation. In conclusion, older adults have blunted coronary blood flow responses to isometric exercise.

Acute cold exposure and cognitive function: evidence for sustained impairment

Several industries experience periods of cold exposure and rewarming throughout the workday but mental performance under these conditions is unknown. A better understanding of cognition during the rewarming phase after cold exposure may help reduce accidents and improve performance. Ten young men (wearing ∼0.1 clo) underwent three consecutive mornings trials where they were exposed to cold air (10°C) and then subsequently rewarmed (25°C air). A computerised test battery was administered during each stage of the protocol to determine working memory, choice reaction time, executive function and maze navigation. Rectal and skin temperature, oxygen consumption and thermal sensation were also measured throughout and showed a typical response. Relative to baseline performance, working memory, choice reaction time and executive function declined during exposure to 10°C, and these impairments persisted 60 min into the recovery period (i.e. once physiological parameters had returned to baseline). Further work is needed to develop countermeasures to this predicament. Practitioner Summary: This study showed that working memory, choice reaction time and executive function declined during exposure to 10°C air, and these impairments persisted 60 min into the rewarming period (i.e. once measurable physiological parameters had returned to normal). Individuals may be at risk for injury after removal from a cold environment.

Mental Stress Elicits Sustained and Reproducible Increases in Skin Sympathetic Nerve Activity.

Mental stress (MS) is a known trigger of myocardial infarction and sudden death. By activating the sympathetic nervous system, MS may have deleterious effect on the cardiovascular system but this process is not completely understood. The primary aim of this study was to quantify the effect of MS on skin sympathetic nerve activity (SSNA). The secondary aim was to determine the reproducibility of SSNA to MS within a given day and ~1 week later. Ten subjects (26 ± 1 year) performed two bouts of mental arithmetic lasting 3 min. The bouts were separated by 45 min. One week later the subjects returned to repeat MS. All experiments were conducted in the supine posture during the morning hours. To maintain neutral skin temperature, each subject wore a custom suit (34–35°C). Skin blood flow and sweat rate were measured on the dorsal foot. MS elicited a marked increase in SSNA within the first 10 sec (184 ± 42%; P < 0.01) in all subjects, which was less during the remaining period of MS, but remained elevated (87 ± 20; P < 0.01). The pattern of responses to MS was unchanged during the second bout (10 sec, 247 ± 55%; 3 min average, 133 ± 29%) and during the retest 1 week later (10 sec, 196 ± 55%; 3 min average, 117 ± 36%). MS did not significantly affect cutaneous vascular conductance or sweat rate during any trial. In summary, MS elicits robust and reproducible increases in SSNA in humans, which may be followed over time to observe alterations in the regulation of the autonomic nervous system.

THE EFFECTS OF COMBINED ELASTIC- AND FREE-WEIGHT TENSION VS. FREE-WEIGHT TENSION ON ONE-REPETITION MAXIMUM STRENGTH IN THE BENCH PRESS

Bellar, DM, Muller, MD, Barkley, JE, Kim, C-H, Ida, K, Ryan, EJ, Bliss, MV, and Glickman, EL. The effects of combined elastic- and free-weight tension vs. free-weight tension on one-repetition maximum strength in the bench press J Strength Cond Res 25(2): 459-463, 2011-The present study investigated the effects of training combining elastic tension, free weights, and the bench press. Eleven college-aged men (untrained) in the bench press participated in the 13-week study. The participants were first given instructions and then practiced the bench press, followed by a one-repetition maximum (1RM) test of baseline strength. Subjects were then trained in the bench press for 3 weeks to allow for the beginning of neural adaptation. After another 1RM test, participants were assigned to 1 of 2 conditions for the next 3 weeks of training: 85% Free-Weight Tension, 15% Elastic Tension (BAND), or 100% Free-Weight Tension (STAND). After 3 weeks of training and a third 1RM max test, participants switched treatments, under which they completed the final 3 weeks of training and the fourth 1RM test. Analysis via analysis of covariance revealed a significant (p ≤ 0.05) main effect for time and interaction effect for Treatment (BAND vs. STAND). Subsequent analysis via paired-samples t-test revealed the BAND condition was significantly better (p = 0.05) at producing raw gains in 1RM strength. (BAND 9.95 ± 3.7 kg vs. STAND 7.56 ± 2.8 kg). These results suggest that the addition of elastic tension to the bench press may be an effective method of increasing strength.

Effect of healthy aging on renal vascular responses to local cooling and apnea.

Sympathetically mediated renal vasoconstriction may contribute to the pathogenesis of hypertension in older adults, but empirical data in support of this concept are lacking. In 10 young (26 ± 1 yr) and 11 older (67 ± 2 yr) subjects, we quantified acute hemodynamic responses to three sympathoexcitatory stimuli: local cooling of the forehead, cold pressor test (CPT), and voluntary apnea. We hypothesized that all stimuli would increase mean arterial blood pressure (MAP) and renal vascular resistance index (RVRI) and that aging would augment these effects. Beat-by-beat MAP, heart rate (HR), and renal blood flow velocity (from Doppler) were measured in the supine posture, and changes from baseline were compared between groups. In response to 1°C forehead cooling, aging was associated with an augmented MAP (20 ± 3 vs. 6 ± 2 mmHg) and RVRI (35 ± 6 vs. 16 ± 9%) but not HR. In older adults, there was a positive correlation between the cold-induced pressor response and forehead pain (R = 0.726), but this effect was not observed in young subjects. The CPT raised RVRI in both young (56 ± 13%) and older (45 ± 8%) subjects, but this was not different between groups. Relative to baseline, end-expiratory apnea increased RVRI to a similar extent in both young (46 ± 14%) and older (41 ± 9%) subjects. During sympathetic activation, renal vasoconstriction occurred in both groups. Forehead cooling caused an augmented pressor response in older adults that was related to pain perception.

Melatonin attenuates the skin sympathetic nerve response to mental stress

Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli, but it is unknown whether melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo-controlled, crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days. Three minutes of mental stress occurred before and 45 min after ingestion of melatonin (3 mg) or placebo. Skin temperature was maintained at 34°C. Reflex increases in SSNA (peroneal nerve), mean arterial pressure, and heart rate (HR) to mental stress before and after melatonin were determined. Melatonin lowered HR (pre, 66 ± 3 beats/min; and post, 62 ± 3 beats/min, P = 0.046) and SSNA (pre, 14,282 ± 3,706 arbitrary units; and post, 9,571 ± 2,609 arbitrary units, P = 0.034) at rest. In response to mental stress, SSNA increases were significantly attenuated following melatonin ingestion (second minute, 114 ± 30 vs. 74 ± 14%; and third minute, 111 ± 29 vs. 54 ± 12%, both P < 0.05). The mean arterial pressure increase to mental stress was blunted in the third minute (20 ± 2 vs. 17 ± 2 mmHg, P = 0.032), and the HR increase was blunted in the first minute (33 ± 3 vs. 29 ± 3 beats/min, P = 0.034) after melatonin. In summary, exogenous melatonin attenuates the SSNA response to mental stress.

Coronary responses to cold air inhalation following afferent and efferent blockade

Cardiac ischemia and angina pectoris are commonly experienced during exertion in a cold environment. In the current study we tested the hypotheses that oropharyngeal afferent blockade (i.e., local anesthesia of the upper airway with lidocaine) as well as systemic β-adrenergic receptor blockade (i.e., intravenous propranolol) would improve the balance between myocardial oxygen supply and demand in response to the combined stimulus of cold air inhalation (-15 to -30°C) and isometric handgrip exercise (Cold + Grip). Young healthy subjects underwent Cold + Grip following lidocaine, propranolol, and control (no drug). Heart rate, blood pressure, and coronary blood flow velocity (CBV, from Doppler echocardiography) were continuously measured. Rate-pressure product (RPP) was calculated, and changes from baseline were compared between treatments. The change in RPP at the end of Cold + Grip was not different between lidocaine (2,441 ± 376) and control conditions (3,159 ± 626); CBV responses were also not different between treatments. With propranolol, heart rate (8 ± 1 vs. 14 ± 3 beats/min) and RPP responses to Cold + Grip were significantly attenuated. However, at peak exercise propranolol also resulted in a smaller ΔCBV (1.4 ± 0.8 vs. 5.3 ± 1.4 cm/s, P = 0.035), such that the relationship between coronary flow and cardiac metabolism was impaired under propranolol (0.43 ± 0.37 vs. 2.1 ± 0.63 arbitrary units). These data suggest that cold air breathing and isometric exercise significantly influence efferent control of coronary blood flow. Additionally, β-adrenergic vasodilation may play a significant role in coronary regulation during exercise.

Cardiac mechanics are impaired during fatiguing exercise and cold pressor test in healthy older adults.

We sought to determine how the aging left ventricle (LV) responds to sympathetic nervous system (SNS) activation. Three separate echocardiographic experiments were conducted in 11 healthy young (26 ± 1 yr) and 11 healthy older (64 ± 1 yr) adults. Tissue Doppler imaging was used to measure systolic myocardial velocity (S(m)), early diastolic myocardial velocity (E(m)), and late diastolic myocardial velocity (A(m)) during isometric fatiguing handgrip (IFHG), a 2-min cold pressor test (CPT), and 5 min of normobaric hypoxia. Heart rate (HR) and mean arterial pressure (MAP) were also monitored on a beat-by-beat basis; rate pressure product (RPP) was used as an index of myocardial oxygen demand. At peak IFHG, the groups had similar increases in RPP, but the ΔS(m) was significantly greater (i.e., larger impairment) in the older subjects (-0.82 ± 0.13 cm/s) compared with the young subjects (0.37 ± 0.30 cm/s). At peak IFHG, the ΔE(m) was similar between older (-1.59 ± 0.68 cm/s) and young subjects (-1.06 ± 0.76 cm/s). In response to the CPT, both S(m) and E(m) were reduced in the older adults but did not change relative to baseline in the young subjects. Normobaric hypoxia elevated HR and RPP in both groups but did not alter Tissue Doppler parameters. These data indicate that S(m) and E(m) are reduced in healthy older adults during IFHG and CPT. We speculate that suboptimal LV adaptations to SNS stress may partly explain why acute heavy exertion can trigger myocardial ischemia.