This is a proposal to study physiologic and pathophysiologic autonomic cardiovascular control mechanisms, and to assess implications of the derangements of autonomic control that occur in patients with cardiovascular diseases. All of this research will be conducted with human volunteers. Subjects will include healthy young and middle-aged adults, patients with orthotopic cardiac transplants, post-myocardial infarction patients, and patients with congestive heart failure. Autonomic inputs will be altered with aerobic exercise and changes of respiratory rate, depth, and resistance, heart rate and rhythm, and arterial pressure. Measured autonomic cardiovascular responses will include estimates of vagal-cardiac nerve activity (standard deviations of R-R interval or respiratory peak-valley R-R interval changes) and sympathetic activity (antecubital vein plasma norepinephrine or directly measured postganglionic muscle sympathetic nerve activity). The proposed studies will address important basic, methodologic, and clinical problems. Basic physiologic issues include how changes of autonomic sensory input are translated into changes of autonomic cardiovascular output; how respiration modulates oscillations of sympathetic activity; and how simultaneous changes of arterial pressure and respiration modify autonomic activity. In the course of the proposed studies, important methodologic issues will be addressed critically; in particular, efforts will be expended to understand better the significance and limitations of venous plasma norepinephrine, muscle sympathetic nerve activity, and low frequency R-R power spectral density as reflections of sympathetic activity. The major thrust of the proposal will be to better understand pathophysiologic mechanisms in patients with cardiovascular diseases. In particular, studies will be directed towards understanding why sympathetic activity is high in these patients, why the immediate post-exercise period presents such extraordinary risk to these patients, and what role, if any, acute or chronic reductions of vagal-cardiac nerve activity or increases of sympathetic nerve activity play in the genesis of sudden cardiac death. These questions are large and have enormous public health significance; the research approaches that will be used have a substantial likelihood of providing scientifically credible, unique, new information.
| Diedrich, André; Crossman, Alexandra A; Beightol, Larry A et al. (2013) Baroreflex physiology studied in healthy subjects with very infrequent muscle sympathetic bursts. J Appl Physiol (1985) 114:203-10 |
| Rothlisberger, Brian W; Badra, Leslie J; Hoag, Jeffrey B et al. (2003) Spontaneous 'baroreflex sequences' occur as deterministic functions of breathing phase. Clin Physiol Funct Imaging 23:307-13 |
| Badra, L J; Cooke, W H; Hoag, J B et al. (2001) Respiratory modulation of human autonomic rhythms. Am J Physiol Heart Circ Physiol 280:H2674-88 |
| Gonschorek, A S; Lu, L L; Halliwill, J R et al. (2001) Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms. Clin Physiol 21:323-34 |
| Taylor, J A; Myers, C W; Halliwill, J R et al. (2001) Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans. Am J Physiol Heart Circ Physiol 280:H2804-14 |
| Cooke, W H; Ames JE, I V; Crossman, A A et al. (2000) Nine months in space: effects on human autonomic cardiovascular regulation. J Appl Physiol 89:1039-45 |
| Cooke, W H; Hoag, J B; Crossman, A A et al. (1999) Human responses to upright tilt: a window on central autonomic integration. J Physiol 517 ( Pt 2):617-28 |
| Rudas, L; Crossman, A A; Morillo, C A et al. (1999) Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine. Am J Physiol 276:H1691-8 |
| Taylor, J A; Carr, D L; Myers, C W et al. (1998) Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation 98:547-55 |
| Koh, J; Brown, T E; Beightol, L A et al. (1998) Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations. J Auton Nerv Syst 68:89-95 |
Showing the most recent 10 out of 58 publications
