Cheryl Blaha

Muscle sympathetic nerve activity responses to dynamic passive muscle stretch in humans

It is suggested that mechanoreceptors in muscle play an important role in the exercise pressor reflex. However, it has not been verified whether isolated stimulation of the mechanoreceptors can induce responses in muscle sympathetic nerve activity (MSNA) in young healthy individuals. We tested the hypothesis that passive stretch of muscle can evoke an increase in MSNA in healthy individuals. In 12 young subjects, leg calf muscles were passively stretched, or actively contracted for 5 s followed by a 15–25 s (random length) relaxation period. Stretch and contraction were each repeated 25 times. MSNA, heart rate and blood pressure were analysed, and averaged according to the onset of the force on a beat‐by‐beat basis. At the 1st to the 3rd heart beat from the onset of stretch, MSNA (199 ± 30%, P < 0.05) as well as heart rate (102.5 ± 0.7%, P < 0.05) increased transiently but significantly from the prior stretch baseline (100%), followed (from 3rd to 7th beat from the onset of stretch) by a transient increase in mean blood pressure (101.9 ± 0.3%, P < 0.05) from the baseline. Similar response patterns were observed during active muscle contractions. The present data show that MSNA responses to isolated stimulation of mechanoreceptors are measurable. Because of baroreflex engagement, the magnitude of the response is small and transient, and the haemodynamic consequences using this protocol may be limited.

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.

Changes of central haemodynamic parameters during mental stress and acute bouts of static and dynamic exercise

Chronic dynamic (aerobic) exercise decreases central arterial stiffness, whereas chronic resistance exercise evokes the opposite effect. Nevertheless, there is little information available on the effects of acute bouts of exercise. Also, there is limited data showing an increase of central arterial stiffness during acute mental stress. This study aimed to determine the effect of acute mental and physical (static and dynamic exercise) stress on indices of central arterial stiffness. Fifteen young healthy volunteers were studied. The following paradigms were performed: (1) 2 min of mental arithmetic, (2) short bouts (20 s) of static handgrip at 20 and 70% of maximal voluntary contraction (MVC), (3) fatiguing handgrip at 40% MVC and (4) incremental dynamic knee extensor exercise. Central aortic waveforms were assessed using SphygmoCor software. As compared to baseline, pulse wave transit time decreased significantly for all four interventions indicating that central arterial stiffness increased. During fatiguing handgrip there was a fall in the ratio of peripheral to central pulse pressure from 1.69±0.02 at baseline to 1.56±0.05 (P<0.05). In the knee extensor protocol a non-significant trend for the opposite effect was noted. The augmentation index increased significantly during the arithmetic, short static and fatiguing handgrip protocols, whereas there was no change in the knee extensor protocol. We conclude that (1) during all types of acute stress tested in this study (including dynamic exercise) estimated central stiffness increased, (2) during static exercise the workload posed on the left ventricle (expressed as change in central pulse pressure) is relatively higher than that posed during dynamic exercise (given the same pulse pressure change in the periphery).

Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.

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.

Effect of P2 receptor blockade with pyridoxine on sympathetic response to exercise pressor reflex in humans

During exercise, sympathetic nervous system activity increases and this contributes to an increase in blood pressure (i.e. exercise pressor reflex). Although animal studies suggest that purinergic P2 receptors on thin fibre sensory nerves are stimulated and evoke this reflex, human data are lacking. In this study, young healthy volunteers performed fatiguing isometric handgrip before and after a local infusion of pyridoxine (i.e. vitamin B6) into the ‘isolated’ circulation of the human forearm. Pyridoxine is converted into a P2‐purinoceptor antagonist. Muscle sympathetic nerve activity and blood pressure responses to fatiguing handgrip and post‐exercise circulatory occlusion were significantly less after pyridoxine than they were before. These effects were not observed after infusion of saline. These data suggest that P2 receptors contribute to the exercise pressor reflex in humans.

Chronic Heart Failure Does Not Attenuate the Total Activity of Sympathetic Outflow to Skin During Whole Body Heating

Background—Previous studies show that the rise in skin blood flow and cutaneous vascular conductance during heat stress is substantially attenuated in chronic heart failure (CHF) patients. The mechanisms responsible for this finding are not clear. In particular, little is known regarding the responses of skin sympathetic nerve activity (SSNA) that control the skin blood flow during heat stress in CHF patients. We examined the effects of a modest heat stress to test the hypothesis that SSNA responses could be attenuated in CHF. Methods and Results—We assessed SSNA (microneurography) from the peroneal nerve and skin blood flow (forearm laser Doppler) in 9 patients with stable class II–III CHF and in matched healthy subjects during passive whole-body heating with a water-perfused suit. Whole-body heating induced similar increases in internal temperature (≈0.6°C) in both groups. Whole-body heat stress evoked similar SSNA activation in CHF patients (&Dgr;891±110 U/min) and the control subjects (&Dgr;787±84 U/min; P=0.66), whereas the elevation in forearm cutaneous vascular conductance in patients with CHF was significantly lower than that in healthy control subjects (&Dgr;131±29% vs &Dgr;623±131%; P=0.001). Conclusions—The present data show that SSNA activation during a modest whole-body heat stress is not attenuated in CHF. Thus, the attenuated skin vasodilator response in CHF patients is not attributable to a reduction in total activity of sympathetic outflow to skin.

Partners in Care: a Model of Collaboration.

It is estimated that 3 million persons in the United States have congestive heart failure. This diagnosis accounts for more than 5% of total health expenditures. A method to decrease the costs of health care was initiated through the partners-in-care model of collaborative practice. A research study exploring the use of nurse case managers in collaboration with cardiologists and primary care physicians is being conducted with persons older than 65 years. This care encompasses both inpatient and outpatient care. The intervention comprises nurse visits in the hospital and in the home as well as telephone support for 6 months after the index hospitalization. The outcomes of quality of life, functional status, mortality, morbidity, and costs are being examined. Collaborative health care partnerships may be an effective strategy to decrease health care costs and improve quality of life and functional status of older persons with congestive heart failure.

Renal vasoconstrictor responses to static exercise during orthostatic stress in humans: effects of the muscle mechano‐ and the baroreflexes

Renal circulatory adjustments to stress contribute to blood pressure and volume regulation. Both handgrip (HG) and disengagement of baroreflexes with lower body negative pressure (LBNP) can engage the sympathetic nervous system (SNS). However, the effect of simultaneous HG and LBNP on the renal circulation in humans is not known. Eighteen young healthy volunteers were studied. Beat‐to‐beat changes in renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres) and heart rate (ECG) were monitored during (a) 15 s HG at 30% maximum voluntary contraction (MVC); (b) LBNP at −10 and −30 mmHg (each level for 5 min); and (c) 15 s HG (at 30% MVC) during LBNP at both levels. Renal vascular resistance index (RVR units) was calculated by dividing MAP by RBV. The increases in RVR during HG alone (12 ± 6%) were not different from the responses noted during combined HG and LBNP (17 ± 6% at −10 mmHg and 25 ± 8% at −30 mmHg). These results suggest occlusion occurs between a neural circuit engaged during 15 s of HG (central command and/or the muscle mechanoreflex) and a circuit activated by LBNP. In additional experiments (n= 6), similar non‐algebraic summation of RVR was seen during 15 s involuntary biceps contractions (engages only muscle reflexes) and LBNP. With respect to RVR, neural occlusion occurs between baroreflexes and the muscle mechanoreflex. Muscle mechanoreflex mediated renal vasoconstriction during short bouts of HG is not influenced by baroreflex disengagement.

Muscle oxygenation during dynamic plantar flexion exercise: combining BOLD MRI with traditional physiological measurements

Blood‐oxygen‐level‐dependent magnetic resonance imaging (BOLD MRI) has the potential to quantify skeletal muscle oxygenation with high temporal and high spatial resolution. The purpose of this study was to characterize skeletal muscle BOLD responses during steady‐state plantar flexion exercise (i.e., during the brief rest periods between muscle contraction). We used three different imaging modalities (ultrasound of the popliteal artery, BOLD MRI, and near‐infrared spectroscopy [NIRS]) and two different exercise intensities (2 and 6 kg). Six healthy men underwent three separate protocols of dynamic plantar flexion exercise on separate days and acute physiological responses were measured. Ultrasound studies showed the percent change in popliteal velocity from baseline to the end of exercise was 151 ± 24% during 2 kg and 589 ± 145% during 6 kg. MRI studies showed an abrupt decrease in BOLD signal intensity at the onset of 2 kg exercise, indicating deoxygenation. The BOLD signal was further reduced during 6 kg exercise (compared to 2 kg) at 1 min (−4.3 ± 0.7 vs. −1.2 ± 0.4%, P < 0.001). Similarly, the change in the NIRS muscle oxygen saturation in the medial gastrocnemius was −11 ± 4% at 2 kg and −38 ± 11% with 6 kg (P = 0.041). In conclusion, we demonstrate that BOLD signal intensity decreases during plantar flexion and this effect is augmented at higher exercise workloads.