No abstract

To examine effects of static exercise on the arterial baroreflex control of vascular sympathetic nerve activity, 22 healthy male volunteers performed 2 min of static handgrip exercise at 30% of maximal voluntary force, followed by postexercise circulatory arrest (PE-CA). Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of arterial pressure (Portapres). The relationship between MSNA and diastolic arterial pressure was calculated for each condition and was defined as the arterial baroreflex function. There was a close relationship between MSNA and diastolic arterial pressure in each subject at rest and during static exercise and PE-CA. The slope of the relationship significantly increased by >300% during static exercise (P < 0.001), and the x-axis intercept (diastolic arterial pressure level) increased by 13 mmHg during exercise (P < 0.001). These alterations in the baroreflex relationship were completely maintained during PE-CA. It is concluded that static handgrip exercise is associated with a resetting of the operating range and an increase in the reflex gain of the arterial barorelex control of MSNA.

Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

. Low-frequency oscillation of sympathetic nerve activity decreases during development of tiltinduced syncope preceding sympathetic withdrawal and bradycardia. Am J Physiol Heart Circ Physiol 289: H1758 -H1769, 2005. First published June 2, 2005; doi:10.1152/ajpheart.01027.2004.-Sympathetic activation during orthostatic stress is accompanied by a marked increase in low-frequency (LF, ϳ0.1-Hz) oscillation of sympathetic nerve activity (SNA) when arterial pressure (AP) is well maintained. However, LF oscillation of SNA during development of orthostatic neurally mediated syncope remains unknown. Ten healthy subjects who developed head-up tilt (HUT)-induced syncope and 10 agematched nonsyncopal controls were studied. Nonstationary timedependent changes in calf muscle SNA (MSNA, microneurography), R-R interval, and AP (finger photoplethysmography) variability during a 15-min 60°HUT test were assessed using complex demodulation. In both groups, HUT during the first 5 min increased heart rate, magnitude of MSNA, LF and respiratory high-frequency (HF) amplitudes of MSNA variability, and LF and HF amplitudes of AP variability but decreased HF amplitude of R-R interval variability (index of cardiac vagal nerve activity). In the nonsyncopal group, these changes were sustained throughout HUT. In the syncopal group, systolic AP decreased from 100 to 60 s before onset of syncope; LF amplitude of MSNA variability decreased, whereas magnitude of MSNA and LF amplitude of AP variability remained elevated. From 60 s before onset of syncope, MSNA and heart rate decreased, index of cardiac vagal nerve activity increased, and AP further decreased to the level at syncope. LF oscillation of MSNA variability decreased during development of orthostatic neurally mediated syncope, preceding sympathetic withdrawal, bradycardia, and severe hypotension, to the level at syncope. autonomic nervous system; baroreflex; blood pressure; heart rate variability; hemodynamics HUMANS HAVE BEEN SUBJECTED to ceaseless orthostatic stresses since they first evolved and assume an orthostatic posture for most of their lives. During standing, gravitational fluid shift toward the lower part of body (i.e., abdominal vascular bed and lower limbs) would cause severe orthostatic hypotension if it were not countered by compensatory mechanisms (23). Orthostatic sympathetic activation has a crucial role in preventing orthostatic hypotension and maintaining arterial blood pressure (AP) (23). Recent studies have reported that orthostatic sympathetic activation is accompanied by an increase in lowfrequency (LF, ϳ0.1-Hz) oscillation of sympathetic nerve activity (SNA) (1, 5). Tilt maneuvers of 75°and 80°greatly increase the LF oscillatory patterns of muscle SNA (MSNA), which mirrored similar changes in LF oscillation of AP (1, 5). However, LF oscillation of SNA has been investigated only in the steady-state orthostatic condition, when AP remains well maintained. It remains unclear whether LF oscillation of SNA changes during development of orthostatic neurally mediated s...

To examine how long-lasting microgravity simulated by 6 degrees head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60 degrees HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60 degrees HUT was not different between before and after HDBR, but mean blood pressure decreased in 60 degrees HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.

Grb2-associated binder (Gab) family of scaffolding adaptor proteins coordinate signaling cascades downstream of growth factor and cytokine receptors. In the heart, among EGF family members, neuregulin-1β (NRG-1β, a paracrine factor produced from endothelium) induced remarkable tyrosine phosphorylation of Gab1 and Gab2 via erythroblastic leukemia viral oncogene (ErbB) receptors. We examined the role of Gab family proteins in NRG-1β/ErbB-mediated signal in the heart by creating cardiomyocyte-specific Gab1/Gab2 double knockout mice (DKO mice). Although DKO mice were viable, they exhibited marked ventricular dilatation and reduced contractility with aging. DKO mice showed high mortality after birth because of heart failure. In addition, we noticed remarkable endocardial fibroelastosis and increase of abnormally dilated vessels in the ventricles of DKO mice. NRG-1β induced activation of both ERK and AKT in the hearts of control mice but not in those of DKO mice. Using DNA microarray analysis, we found that stimulation with NRG-1β upregulated expression of an endothelium-stabilizing factor, angiopoietin 1, in the hearts of control mice but not in those of DKO mice, which accounted for the pathological abnormalities in the DKO hearts. Taken together, our observations indicated that in the NRG-1β/ErbB signaling, Gab1 and Gab2 of the myocardium are essential for both maintenance of myocardial function and stabilization of cardiac capillary and endocardial endothelium in the postnatal heart.

We estimated open-loop dynamic characteristics of the carotid sinus baroreflex in normal control rats and chronic heart failure (CHF) rats after myocardial infarction. First, the neural arc transfer function from carotid sinus pressure to splanchnic sympathetic nerve activity (SNA) and its corresponding step response were examined. Although the steady-state response was attenuated in CHF, the negative peak response and the time to peak did not change significantly, suggesting preserved neural arc dynamic characteristics. Next, the peripheral arc transfer function from SNA to arterial pressure (AP) and its corresponding step response were examined. The steady-state response and the initial slope were reduced in CHF, suggesting impaired end-organ responses. In a simulation study based on the dynamic and static characteristics, the percent recovery of AP was reduced progressively as the size of disturbance increased in CHF, suggesting that a reserve for AP buffering is lost in CHF despite relatively maintained baseline AP.

A novel framework of circulatory equilibrium was developed by extending Guyton's original concept. In this framework, venous return (CO V) for a given stressed volume (V) was characterized by a flat surface as a function of right atrial pressure (P RA) and left atrial pressure (PLA) as follows: COV ϭ V/W Ϫ G SPRA Ϫ GPPLA, where W, GS, and GP denote linear parameters. In seven dogs under total heart bypass, CO V, PRA, PLA, and V were varied to determine the three parameters in each animal with use of multivariate analysis. The coefficient of determination (r 2 ϭ 0.92-0.99) indicated the flatness of the venous return surface. The averaged surface was CO V ϭ V/0.129 Ϫ 19.61PRA Ϫ 3.49PLA. To examine the invariability of the surface parameters among animals, we predicted the circulatory equilibrium in response to changes in stressed volume in another 12 dogs under normal and heart failure conditions. This was achieved by equating the standard surface with the individually measured cardiac output (CO) curve. In this way, we could predict CO [y ϭ 0.90x ϩ 5.6, r 2 ϭ 0.95, standard error of the estimate (SEE) ϭ 8.7 ml ⅐ min Ϫ1 ⅐ kg Ϫ1 ], PRA (y ϭ 0.96x, r 2 ϭ 0.98, SEE ϭ 0.2 mmHg), and P LA (y ϭ 0.89x ϩ 0.5, r 2 ϭ 0.98, SEE ϭ 0.8 mmHg) reasonably well. We conclude that the venous return surface accurately represents the venous return properties of the systemic and pulmonary circulations. The characteristics of the venous return surface are invariable enough among animals, making it possible to predict circulatory equilibrium, even if those characteristics are unknown in individual animals. venous return; cardiac output; hemodynamics THE FRAMEWORK FOR CIRCULATORY EQUILIBRIUM was pioneered by Guyton and associates in the 1950s (14 -17). They characterized the venous return properties of the systemic vein by the venous return curve and the apparent pumping ability of the cardiothoracic compartment by the cardiac output (CO) curve (Fig. 1A). The intersection of the two curves determines equilibrium CO and right atrial pressure (P RA ) (14). This concept clearly defined the circulatory equilibrium under rather simple pathophysiological conditions, such as hemorrhage and exercise, and deepened our understanding of control mechanisms of CO. However, because the original framework lumped various subsystem components, such as the right ventricle, pulmonary vascular system, and left ventricle, into a single cardiothoracic compartment, the lack of consideration of the venous return properties of the pulmonary circulation and the pumping ability of the individual ventricles makes it difficult to define the circulatory equilibrium under more complex conditions such as unilateral ventricular failures, which are often seen in clinical settings (2). In other words, redistribution of blood between the systemic and pulmonary circulations cannot be defined by their original framework.To deal with the blood redistribution, Guyton et al. (15) modified the original framework and developed a two-compartment model. However, the analysis of hem...