Neural control of the cardiovascular system: insights from muscle sympathetic nerve recordings in humans.

The regulation of the heart and peripheral circulation by the nervous system is accomplished by control centers in the medulla that receive descending input from higher neural areas in the brain and afferent input from mechanically and chemically sensitive receptors located throughout the body. The resultant changes in efferent sympathetic and parasympathetic activity allow rapid cardiovascular responses during a number of physiological perturbations including changes in posture, physical activity, temperature, altitude, and microgravity. The ability to record sympathetic nerve activity targeted to the skeletal muscle vasculature with intraneural microelectrodes has provided a powerful new tool to study fundamental mechanisms of neurocirculatory regulation in conscious human subjects.

Excitatory amino acid concentrations in the spinal dorsal horn of cats during muscle contraction.

In anesthetized cats, static hindlimb muscle contraction reflexly increases mean arterial pressure (MAP) and heart rate (HR). Pharmacological and immunohistochemical evidence suggests that excitatory amino acids are involved in the spinal transmission of this reflex. Using microdialysis and high-performance liquid chromatography technology, we tested the hypothesis that static contraction of the triceps surae muscle increases the extracellular concentration of glutamate (Glu) and aspartate (Asp) at the L7 level of the dorsal horn of the spinal cord.

Cardiovascular responses at the onset of static exercise in patients with dual-chamber pacemakers.

Cardiac output (CO) responses to exercise can be altered by ventricular pacing in pacemaker-dependent patients. The relative contributions of CO and peripheral vascular resistance (PVR) toward the initial increase in blood pressure with the initiation of static exercise were investigated in eight otherwise healthy pacemaker-dependent subjects [age 24 +/- 2 yr (range 17-37 yr)]. Beat-by-beat measures of heart rate (HR; electrocardiography), mean arterial pressure (MAP), and CO derived from stroke volume (SV) (CO = HR.

Left ventricular volumes and hemodynamic responses at onset of dynamic exercise with reduced venous return.

The hemodynamic effects of reducing venous return were assessed beat by beat at the onset of upright dynamic exercise. Mean arterial pressure (MAP), heart rate, and left ventricular end-systolic (ESV) and end-diastolic volumes (EDV; two-dimensional echocardiography) were measured in 10 healthy men during 20-s trials of upright cycling (30 W; 60 rpm). Exercise was performed either with or without venous occlusion of the legs (bilateral thigh cuffs inflated to 100 mmHg) in a random order.

Cardiovascular effects elicited by central administration of physostigmine via M2 muscarinic receptors in conscious cats.

The cardiovascular effects of an intracerebroventricular (i.c.v.

Modulation of reflex pressor response to contraction and effect on substance P release by spinal 5-HT1A receptors.

This study investigated whether activation of serotonin1A [5-hydroxytryptamine (5-HT)1A] receptors in the dorsal horn of the spinal cord attenuates the reflex pressor response to static contraction and passive muscle stretch. In addition, we determined if the attenuation of the response to contraction is mediated by inhibiting substance P (SP) release in the dorsal horn. Static contractions of the triceps surae muscle of chloralose-anesthetized cats were induced by stimulating the cut L7 and S1 ventral roots.

Effects of clonidine on the reflex cardiovascular responses and release of substance P during muscle contraction.

The effects of microdialyzing clonidine into the L-7 dorsal horn on the cardiovascular responses, renal sympathetic nerve activity (RSNA), and release of substance P (SP) evoked by static contraction of the triceps surae muscle were studied using anesthetized cats. A microdialysis probe was inserted into the spinal cord ipsilateral to the muscle being contracted or stretched. Contraction, evoked by stimulation of the distal ends of the cut L-7 and S-1 ventral roots for 1 minute, increased mean arterial pressure (MAP), heart rate (HR), and RSNA by 48 +/- 6 mm Hg, 18 +/- 2 beats per minute, and 66 +/- 5%, respectively.

Cardiovascular responses to active and passive cycling movements.

Ten healthy subjects were evaluated at rest and at 5 min of unloaded active (AC) and passive (PC) cycling. Passive limb movements were accomplished using a tandem bicycle with a second rider performing the movements. We measured heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), oxygen uptake (VO2), rating of perceived exertion (RPE), and electrical activity (EMG) of lower limbs muscles.

Cardiovascular responses during static exercise. Studies in patients with complete heart block and dual chamber pacemakers.

Background: During static exercise in normal subjects, the mean arterial pressure increases as a result of an increase in heart rate and thereby cardiac output with no significant change in stroke volume or systemic vascular resistance. We hypothesized that if one component of the blood pressure response to static exercise, ie, heart rate, were fixed, plasticity of the neural control mechanisms during exercise would allow for preservation of the blood pressure response by alternative mechanisms.

Methods And Results: Thirteen patients 20 to 68 years old with structurally normal hearts, complete heart block, and dual chamber pacemakers performed static exercise during three conditions: (1) normal dual chamber sensing and pacing mode, (2) heart rate fixed at the resting value obtained in the DDD mode of 78 +/- 4 beats per minute, and (3) heart rate fixed at the peak value obtained during exercise in the DDD mode of 94 +/- 4 beats per minute.

Reflex control of glucoregulatory exercise responses by group III and IV muscle afferents.

Group III and IV muscle afferents are active during exercise and relay information from mechano- and metaboreceptors in muscle. We hypothesized that these afferents participate in the regulation of endocrine and metabolic adjustments to exercise. Muscle branches of the femoral nerves were electrically stimulated in 10 anesthetized and paralyzed cats at 3, 20, and 140 times motor threshold, for 10 min at each intensity, recruiting group III afferents at 20 times motor threshold and group III and IV afferents at 140 times motor threshold.

Heart rate and blood pressure responses at the onset of dynamic exercise: effect of Valsalva manoeuvre.

The influence of respiration on the mean blood pressure (Pa) and R-R interval responses at the onset of dynamic exercise was studied in 15 healthy subjects who performed 4 s of unloaded cycling at 1.5-2.0 Hz, 4 s of Valsalva manoeuvre at 5.

Determinants of VO2peak in patients with end-stage renal disease: on and off dialysis.

Peak oxygen uptake (VO2peak) of patients on maintenance hemodialysis is very low. Exercise training performed during, or "on" dialysis, and at other times, "off" dialysis, both improve VO2peak. Equivalence of these approaches has not been shown, nor have the physiologic factors limiting VO2peak been clarified in these patients.

Cardiovascular responses to voluntary and nonvoluntary static exercise in humans.

We have measured the cardiovascular responses during voluntary and nonvoluntary (electrically induced) one-leg static exercise in humans. Eight normal subjects were studied at rest and during 5 min of static leg extension at 20% of maximal voluntary contraction performed voluntarily and nonvoluntarily in random order. Heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were determined, and peripheral vascular resistance (PVR) and stroke volume (SV) were calculated.

Static muscle contraction reflexly increases adrenal sympathetic nerve activity in rats.

Little is known about the mechanisms responsible for activation of sympathoadrenal function during exercise. We hypothesized that sympathoadrenal discharge is activated at the onset of exercise by a reflex arising in the contracting muscle. Adrenal sympathetic nerve activity (SNA) was recorded during 1 min stimulation of the tibial nerve at two times motor threshold, before and during neuromuscular blockade, in 12 alpha-chloralose-anesthetized rats.

Arterial baroreflex buffering of sympathetic activation during exercise-induced elevations in arterial pressure.

Static muscle contraction activates metabolically sensitive muscle afferents that reflexively increase sympathetic nerve activity and arterial pressure. To determine if this contraction-induced reflex is modulated by the sinoaortic baroreflex, we performed microelectrode recordings of sympathetic nerve activity to resting leg muscle during static handgrip in humans while attempting to clamp the level of baroreflex stimulation by controlling the exercise-induced rise in blood pressure with pharmacologic agents. The principal new finding is that partial pharmacologic suppression of the rise in blood pressure during static handgrip (nitroprusside infusion) augmented the exercise-induced increases in heart rate and sympathetic activity by greater than 300%.

Impairment of sympathetic activation during static exercise in patients with muscle phosphorylase deficiency (McArdle's disease).

Static exercise in normal humans causes reflex increases in muscle sympathetic nerve activity (MSNA) that are closely coupled to the contraction-induced decrease in muscle cell pH, an index of glycogen degradation and glycolytic flux. To determine if sympathetic activation is attenuated when muscle glycogenolysis is blocked due to myophosphorylase deficiency (McArdle's disease), an inborn enzymatic defect localized to skeletal muscle, we now have performed microelectrode recordings of MSNA in four patients with McArdle's disease during static handgrip contraction. A level of static handgrip that more than doubled MSNA in normal humans had no effect on MSNA and caused an attenuated rise in blood pressure in the patients with myophosphorylase deficiency.

Mobilization of glucoregulatory hormones and glucose by hypothalamic locomotor centers.

Recent studies suggest that, in addition to classical humoral metabolic feedback mechanisms, the mobilization of glucoregulatory hormones and glucose in exercise may be regulated by motor centers in the brain. We, therefore, studied the effect of electrically stimulating the posterior hypothalamic locomotor region (PHLR) for 10 min in decorticated (n = 6) and alpha-chloralose-anesthetized (n = 8) cats. Blood pressure and heart rate were measured, and blood samples were drawn for analysis of hormones and metabolites before, during, and after 10 min of PHLR stimulation.

Sympathetic nerve discharge is coupled to muscle cell pH during exercise in humans.

We used phosphorus nuclear magnetic resonance spectroscopy (31P-NMR) to probe the cellular events in contracting muscle that initiate the reflex stimulation of sympathetic outflow during exercise. In conscious humans, we performed 31P-NMR on exercising forearm muscle and simultaneously recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve to determine if the activation of MSNA is coupled to muscle pH, an index of glycolysis, or to the concentrations (II) of inorganic phosphate (Pi) and adenosine diphosphate (ADP) which are modulators of mitochondrial respiration. During both static and rhythmic handgrip, the onset of sympathetic activation in resting muscle coincided with the development of cellular acidification in active muscle.

Cardiovascular responses at the onset of exercise with partial neuromuscular blockade in cat and man.

1. In decerebrated cats the cardiovascular, heart rate and blood pressure responses to static muscle contractions were followed from the onset of stimulation of the cut L7-S1 ventral roots. Heart rate and blood pressure were also followed during maximal voluntary and electrically induced static muscle contractions in man using one leg.