Kari U. O. Tahvanainen

Human responses to upright tilt: a window on central autonomic integration

1 We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2 We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min−1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head‐up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low‐frequency (0.05‐0.15 Hz) and respiratory‐frequency (0.15‐0.5 Hz) spectral powers. 3 Integrated areas of muscle sympathetic bursts and their low‐ and respiratory‐frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low‐frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4 Systolic and diastolic pressures and their low‐ and respiratory‐frequency spectral powers increased, and R‐R intervals and their respiratory‐frequency spectral power decreased progressively with the tilt angle. Low‐frequency R‐R interval spectral power did not change. 5 The cross‐spectral phase angle between systolic pressures and R‐R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low‐frequency cross‐spectra, decreased at high tilt angles. 6 Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low‐frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Heart rate variability biofeedback increases baroreflex gain and peak expiratory flow.

Objective We evaluated heart rate variability biofeedback as a method for increasing vagal baroreflex gain and improving pulmonary function among 54 healthy adults. Methods We compared 10 sessions of biofeedback training with an uninstructed control. Cognitive and physiological effects were measured in four of the sessions. Results We found acute increases in low-frequency and total spectrum heart rate variability, and in vagal baroreflex gain, correlated with slow breathing during biofeedback periods. Increased baseline baroreflex gain also occurred across sessions in the biofeedback group, independent of respiratory changes, and peak expiratory flow increased in this group, independently of cardiovascular changes. Biofeedback was accompanied by fewer adverse relaxation side effects than the control condition. Conclusions Heart rate variability biofeedback had strong long-term influences on resting baroreflex gain and pulmonary function. It should be examined as a method for treating cardiovascular and pulmonary diseases. Also, this study demonstrates neuroplasticity of the baroreflex.

Vagal and Sympathetic Mechanisms in Patients With Orthostatic Vasovagal Syncope

BACKGROUNDnAutonomic and particularly sympathetic mechanisms play a central role in the pathophysiology of vasovagal syncope. We report direct measurements of muscle sympathetic nerve activity in patients with orthostatic vasovagal syncope.nnnMETHODS AND RESULTSnWe studied 53 otherwise healthy patients with orthostatic syncope. We measured RR intervals and finger arterial pressures and in 15 patients, peroneal nerve muscle sympathetic activity before and during passive 60 degree head-up tilt, with low-dose intravenous isoproterenol if presyncope did not develop by 15 minutes. We measured baroreflex gain before tilt with regression of RR intervals or sympathetic bursts on systolic or diastolic pressures after sequential injections of nitroprusside and phenylephrine. Orthostatic vasovagal reactions occurred in 21 patients, including 7 microneurography patients. Presyncopal and nonsyncopal patients had similar baseline RR intervals, arterial pressure, and muscle sympathetic nerve activity. Vagal baroreflex responses were significantly impaired at arterial pressures below (but not above) baseline levels in presyncopal patients. Initial responses to tilt were comparable; however, during the final 200 seconds of tilt, presyncopal patients had lower RR intervals and diastolic pressures than nonsyncopal patients and gradual reduction of arterial pressure and sympathetic activity. Frank presyncope began abruptly with precipitous reduction of arterial pressure, disappearance of muscle sympathetic nerve activity, and RR interval lengthening.nnnCONCLUSIONSnPatients with orthostatic vasovagal reactions have impaired vagal baroreflex responses to arterial pressure changes below resting levels but normal initial responses to upright tilt. Subtle vasovagal physiology begins before overt presyncope. The final trigger of human orthostatic vasovagal reactions appears to be the abrupt disappearance of muscle sympathetic nerve activity.

Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine

We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

Noninvasive Detection of Cardiac Sympathetic Nervous Dysfunction in Diabetic Patients Using [123I]Metaiodobenzylguanidine

The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP- group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P < 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P < 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients.

Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre

When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38–44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre‐flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445 % during 30 mmHg straining on earth and 792 % in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.

Impaired left ventricular systolic function during exercise in middle-aged insulin-dependent and noninsulin-dependent diabetic subjects without clinically evident cardiovascular disease

Equilibrium radionuclide angiocardiography was performed on 19 men and 17 women with insulin-dependent diabetes mellitus (IDDM) and on 24 men and 15 women with noninsulin-dependent diabetes mellitus (NIDDM) and on 24 male and 24 female control subjects aged 46 to 67 years. All were without clinically evident cardiovascular disease. No significant differences were found in left ventricular (LV) ejection fraction at rest between men with IDDM (56 +/- 1%; mean +/- standard error of the mean) or NIDDM (58 +/- 1%) and control men (58 +/- 1%), whereas LV ejection fraction was higher in women with IDDM (63 +/- 1%; p less than 0.01) and NIDDM (64 +/- 2%; p less than 0.01) than in control women (58 +/- 1%). An abnormal LV ejection fraction response to dynamic exercise (an increase of less than 5% units or a decrease) was observed in 1 control man (4%), in 8 men with IDDM (42%, p less than 0.01) and in 10 men with NIDDM (42%, p less than 0.01). The respective figures were 4 (17%) for control women, 7 (44%, difference not significant) for women with IDDM and 10 (71%, p less than 0.01) for women with NIDDM. Abnormal LV ejection fraction response to exercise in diabetic patients was not related to the metabolic control of diabetes, presence of microangiopathy or abnormalities in the autonomic nervous function. Myocardial perfusion scintigraphy performed in 18 diabetic patients in whom LV ejection fraction decreased during exercise showed a reversible perfusion defect in only 5 (28%).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac positron emission tomography imaging with [11c]hydroxyephedrine, a specific tracer for sympathetic nerve endings, and its functional correlates in congestive heart failure

The integrative mechanisms of autonomic dysfunction in congestive heart failure (CHF) remain poorly understood. We sought to study cardiac retention of [11C]hydroxyephedrine (HED), a specific tracer for sympathetic presynaptic innervation, and its functional correlates in CHF. Thirty patients with mild to moderate heart failure underwent resting cardiac HED positron emission tomography imaging, spectrum analysis testing of systolic pressure and heart rate variability in the resting supine and 70 degrees head-up tilt positions, and testing of baroreflex sensitivity. Compared with control subjects, global myocardial HED retention index was reduced by 30% (p <0.01) in patients with CHF. The HED retention index did not correlate significantly with heart rate variability. However, it correlated with baroreflex sensitivity at rest (r = 0.43, p = 0.05) and with systolic pressure low-frequency (0.03 to 0.15 Hz) variability at head-up tilt (r = 0.76, p <0.01), as well as with low-frequency systolic pressure variability response from baseline to tilt (r = 0.75, p <0.01). We conclude that cardiac HED retention is reduced in patients with CHF. This correlates with blunted vascular sympathetic effector responses during posture-induced reflex activation and baroreflex control of heart rate, suggesting an interdependence between cardiac presynaptic innervation abnormalities and neural mechanisms important to blood pressure maintenance in CHF.

Simultaneous invasive and noninvasive evaluations of baroreflex sensitivity with bolus phenylephrine technique

Estimation of baroreflex sensitivity (BRS) is receiving increasing attention in clinical and experimental cardiology. Until recently, in most studies BRS has been assessed on the basis of invasive blood pressure measurement, which limits its use in large-scale studies and in clinical practice. The development of continuous noninvasive blood pressure monitoring has made it possible to assess BRS noninvasively. We compared central invasive and peripheral noninvasive techniques in the assessment of BRS during cardiac catheterization in 40 patients with possible coronary artery disease. The correlation between noninvasive and invasive BRS was high (r = 0.92; p < 0.001). However, the noninvasive method resulted in significantly higher BRS values than did the invasive method (7.1 +/- 6.5 msec/mm Hg vs 5.1 +/- 4.3 msec/mm Hg, respectively; p < 0.001) because of the smaller increase in systolic blood pressure after phenylephrine injection by the noninvasive technique than by the invasive technique (18.9 +/- 6.8 mm Hg vs 25.2 +/- 7.8 mm Hg, respectively; p < 0.01). The difference between noninvasive and invasive BRS correlated positively with invasive BRS (r = 0.54; p < 0.001) and inversely with age (r = -0.39; p < 0.01) and resting systolic blood pressure (r = -0.30, p < 0.05). A noninvasive BRS value of < 4.0 ms/mm Hg showed a sensitivity of 94%, a specificity of 91%, and an accuracy of 93% in identifying cases of reduced invasive BRS (< 3.0 msec/mm Hg). Our findings encourage the use of finger-cuff method in the assessment of BRS. However, noninvasive BRS values were slightly but significantly higher than invasive BRS values, a difference that should be taken into account when BRS is measured by the noninvasive approach.

Short-Term Measurement of Heart Rate Variability

The heart is an organ with rich innervation from the parasympathetic and sympathetic limbs of the autonomic nervous system. Although the heart is capable of intrinsic regulation of cardiac rhythm, electrical conduction and contractility, those functions are largely under the control of autonomic nervous system. Particularly, autonomic nervous system is responsible for rapid regulation of cardiac rhythm and pump function in order to match cardiac output with the body needs during various exogenic stimuli of daily life — physical and mental stress, posture changes, etc. Sino-atrial node and atrioventricular node receive both parasympathetic and sympathetic efferent innervation, whereas in the ventricles efferent neural connections are almost solely of sympathetic origin.1 In addition to efferent innervation, the heart has afferent autonomic receptors, which subserve various reflexes originating from the heart.2