Atsunori Kamiya

Effects of increased ambient temperature on skin sympathetic nerve activity and core temperature in humans

The strength of sympathetic vasoconstrictor nerve traffic to the skin has an important role in human thermoregulation since it controls heat loss from the skin by constricting or dilating cutaneous blood vessels. This study sought to clarify the time relationship between a reduction of the vasoconstrictor activity induced by elevating the ambient temperature (Ta), and subsequent change of core temperature (Tty). For this purpose, we recorded peroneal skin sympathetic nerve activity (SSNA), laser Doppler skin blood flow, skin and core (tympanic) temperatures in 11 subjects while increasing Ta from 15 to 30 degrees C during approximately 30 min. We observed a significant suppression of SSNA 7.7 min after Ta rise with marked interindividual variations. Tty displayed an increase with a peak after 8.2 min followed by a successive decrease, which became significant 14 min after the Ta rise. The rate of decrease of vasoconstrictor SSNA correlated both with the rate of decrease of Tty (P<0.01) and the magnitude of the Tty decrease (P<0.0005). A cross-correlogram between SSNA and Tty showed a peak at 7 min (r=0.52). We conclude that a Ta rise-induced reduction of skin vasoconstrictor nerve traffic leads to a core temperature decrease after 7-8 min.

Effects of three days of dry immersion on muscle sympathetic nerve activity and arterial blood pressure in humans.

The present study was performed to determine how sympathetic function is altered by simulated microgravity, dry immersion for 3 days, and to elucidate the mechanism of post-spaceflight orthostatic intolerance in humans. Six healthy men aged 21-36 years old participated in the study. Before and after the dry immersion, subjects performed head-up tilt (HUT) test to 30 degrees and 60 degrees (5 min each) with recordings of muscle sympathetic nerve activity (MSNA, by microneurography), electrocardiogram, and arterial blood pressure (Finapres). Resting MSNA was increased after dry immersion from 23.7+/-3.2 to 40.9+/-3.0 bursts/min (p<0.005) without significant changes in resting heart rate (HR). MSNA responsiveness to orthostasis showed no significant difference but HR response was significantly augmented after dry immersion (p<0. 005). A significant diastolic blood pressure fall at 5th min of 60 degrees HUT was observed in five orthostatic tolerant subjects despite enough MSNA discharge after dry immersion. A subject suffered from presyncope at 2 min after 60 degrees HUT. He showed gradual blood pressure fall 10 s after 60 degrees HUT with initially well-maintained MSNA response and then with a gradually attenuated MSNA, followed by a sudden MSNA withdrawal and abrupt blood pressure drop. In conclusion, dry immersion increased MSNA without changing MSNA response to orthostasis, and resting HR, while increasing the HR response to orthostasis. Analyses of MSNA and blood pressure changes in orthostatic tolerant subjects and a subject with presyncope suggested that not only insufficient vasoconstriction to sympathetic stimuli, but also a central mechanism to induce a sympathetic withdrawal might play a role in the development of orthostatic intolerance after microgravity exposure.

Sympathetic outflow to muscle in humans during short periods of microgravity produced by parabolic flight

We have investigated the changes in muscle sympathetic nerve activity (MSNA) from the tibial nerve during brief periods of microgravity (μG) for ∼20 s produced by parabolic flight. MSNA was recorded microneurographically from 13 quietly seated human subjects with their knee joints extended in a jet aircraft simultaneously with the electrocardiogram, the blood pressure wave (measured with a Finapres), the respiration curve, and the thoracic fluid volume (measured by impedance plethysmography). During quiet and seated parabolic flight, MSNA was activated in hypergravity and was suppressed in μG phasically. At the entry to hypergravity at 2 G just before μG, the thoracic fluid volume was reduced by 3.2 ± 3%, and the arterial blood pressure was lowered transiently and then gradually elevated from 89.5 ± 1.7 to 100.2 ± 1.7 mmHg, which caused the enhancement of MSNA by 91.4 ± 14.2%. At the entry to μG, the thoracic fluid volume was increased by 3.4%, which lowered the mean blood pressure to 77.9 ± 2.3 mmHg and suppressed the MSNA by 17.2%. However, this suppression lasted only ∼10 s, followed by an enhancement of MSNA that continued for several seconds. We conclude that MSNA is suppressed and then enhanced during μG produced by parabolic flight. These changes in MSNA are in response not only to intrathoracic fluid volume changes but also to arterial blood pressure changes, both of which are caused by body fluid shifts induced by parabolic flight, and these changes are quite phasic and transient.We have investigated the changes in muscle sympathetic nerve activity (MSNA) from the tibial nerve during brief periods of microgravity (microG) for approximately 20 s produced by parabolic flight. MSNA was recorded microneurographically from 13 quietly seated human subjects with their knee joints extended in a jet aircraft simultaneously with the electrocardiogram, the blood pressure wave (measured with a Finapres), the respiration curve, and the thoracic fluid volume (measured by impedance plethysmography). During quiet and seated parabolic flight, MSNA was activated in hypergravity and was suppressed in microG phasically. At the entry to hypergravity at 2 G just before microG, the thoracic fluid volume was reduced by 3.2 +/- 3%, and the arterial blood pressure was lowered transiently and then gradually elevated from 89.5 +/- 1.7 to 100.2 +/- 1.7 mmHg, which caused the enhancement of MSNA by 91.4 +/- 14.2%. At the entry to microG, the thoracic fluid volume was increased by 3.4%, which lowered the mean blood pressure to 77.9 +/- 2.3 mmHg and suppressed the MSNA by 17.2%. However, this suppression lasted only approximately 10 s, followed by an enhancement of MSNA that continued for several seconds. We conclude that MSNA is suppressed and then enhanced during microG produced by parabolic flight. These changes in MSNA are in response not only to intrathoracic fluid volume changes but also to arterial blood pressure changes, both of which are caused by body fluid shifts induced by parabolic flight, and these changes are quite phasic and transient.

Assessment of pulse rate variability by the method of pulse frequency demodulation

BackgroundDue to its easy applicability, pulse wave has been proposed as a surrogate of electrocardiogram (ECG) for the analysis of heart rate variability (HRV). However, its smoother waveform precludes accurate measurement of pulse-to-pulse interval by fiducial-point algorithms. Here we report a pulse frequency demodulation (PFDM) technique as a method for extracting instantaneous pulse rate function directly from pulse wave signal and its usefulness for assessing pulse rate variability (PRV).MethodsSimulated pulse wave signals with known pulse interval functions and actual pulse wave signals obtained from 30 subjects with a trans-dermal pulse wave device were analyzed by PFDM. The results were compared with heart rate and HRV assessed from simultaneously recorded ECG.ResultsAnalysis of simulated data revealed that the PFDM faithfully demodulates source interval function with preserving the frequency characteristics of the function, even when the intervals fluctuate rapidly over a wide range and when the signals include fluctuations in pulse height and baseline. Analysis of actual data revealed that individual means of low and high frequency components of PRV showed good agreement with those of HRV (intraclass correlation coefficient, 0.997 and 0.981, respectively).ConclusionThe PFDM of pulse wave signal provides a reliable assessment of PRV. Given the popularity of pulse wave equipments, PFDM may open new ways to the studies of long-term assessment of cardiovascular variability and dynamics.

Open-loop dynamic and static characteristics of the carotid sinus baroreflex in rats with chronic heart failure after myocardial infarction

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.

Responses of muscle sympathetic nerve activity to lower body positive pressure

To evaluate the response of vasomotor sympathetic nerve activity to lower body positive pressure (LBPP), muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve in 10 healthy young men, along with hemodynamic variables and echocardiogram, during exposure to incremental LBPP at 10, 20, and 30 mmHg in the supine position. MSNA was suppressed to a similar extent (27%) at 10- and 20-mmHg LBPP. However, at 30-mmHg LBPP, MSNA tended to increase but was still nearly at the control value. Mean arterial pressure was elevated (11%), total peripheral resistance markedly increased (36%), and stroke volume and cardiac output tended to decrease at 30-mmHg LBPP. Heart rate remained unchanged throughout the procedures. Left atrial dimension significantly increased during 10- and 30-mmHg LBPP, indicating an increased cardiac filling. These results suggest that the inhibitory effect of the cardiopulmonary baroreflex on MSNA at 10- and 20-mmHg LBPP could be counteracted by the sympathoexcitatory effect of the intramuscular pressure-sensitive mechanoreflex at 30-mmHg LBPP. However, the increment of total peripheral resistance at 30-mmHg LBPP may not depend exclusively on this small enhancement of MSNA.To evaluate the response of vasomotor sympathetic nerve activity to lower body positive pressure (LBPP), muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve in 10 healthy young men, along with hemodynamic variables and echocardiogram, during exposure to incremental LBPP at 10, 20, and 30 mmHg in the supine position. MSNA was suppressed to a similar extent (27%) at 10- and 20-mmHg LBPP. However, at 30-mmHg LBPP, MSNA tended to increase but was still nearly at the control value. Mean arterial pressure was elevated (11%), total peripheral resistance markedly increased (36%), and stroke volume and cardiac output tended to decrease at 30-mmHg LBPP. Heart rate remained unchanged throughout the procedures. Left atrial dimension significantly increased during 10- and 30-mmHg LBPP, indicating an increased cardiac filling. These results suggest that the inhibitory effect of the cardiopulmonary baroreflex on MSNA at 10- and 20-mmHg LBPP could be counteracted by the sympathoexcitatory effect of the intramuscular pressure-sensitive mechanoreflex at 30-mmHg LBPP. However, the increment of total peripheral resistance at 30-mmHg LBPP may not depend exclusively on this small enhancement of MSNA.

Muscle Sympathetic Nerve Activity Averaged Over 1 Minute Parallels Renal and Cardiac Sympathetic Nerve Activity in Response to a Forced Baroreceptor Pressure Change

Background—Despite the accumulated knowledge of human muscle sympathetic nerve activity (SNA) as measured by microneurography, whether muscle SNA parallels renal and cardiac SNAs remains unknown. Method and Results—In experiment 1, muscle (microneurography, tibial nerve), renal, and cardiac SNAs were recorded in anesthetized rabbits (n=6) while arterial pressure was changed by intravenous bolus injections of nitroprusside (3 &mgr;g/kg) followed by phenylephrine (3 &mgr;g/kg). In experiment 2, the carotid sinus region was vascularly isolated in anesthetized, vagotomized, and aorta-denervated rabbits (n=10). The 3 SNAs were recorded while intracarotid sinus pressure was increased stepwise from 40 to 160 mm Hg in 20-mm Hg increments maintained for 60 seconds each. Muscle SNA averaged over 1 minute was well correlated with renal (r=0.96±0.01, mean±SE) and cardiac (r=0.96±0.01) SNAs in experiment 1 (baroreflex closed-loop condition) and also with renal (r=0.97±0.01) and cardiac (r=0.97±0.01) SNAs in experiment 2 (baroreflex open-loop condition). Conclusions—Muscle SNA averaged over 1 minute parallels renal and cardiac SNAs in response to a forced baroreceptor pressure change.

Parallel resetting of arterial baroreflex control of renal and cardiac sympathetic nerve activities during upright tilt in rabbits

Since humans are under ceaseless orthostatic stress, the mechanisms to maintain arterial pressure (AP) against gravitational fluid shift are important. As one mechanism, it was reported that upright tilt reset baroreflex control of renal sympathetic nerve activity (SNA) to a higher SNA in anesthetized rabbits. In the present study, we tested the hypothesis that upright tilt causes a parallel resetting of baroreflex control of renal and cardiac SNAs in anesthetized rabbits. In anesthetized rabbits (n = 8, vagotomized and aortic denervated) with 0 degrees supine and 60 degrees upright tilt postures, renal and cardiac SNAs were simultaneously recorded while isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg. Upright tilt shifted the reverse-sigmoidal curve of the CSP-SNA relationship to higher SNA similarly in renal and cardiac SNAs. Although upright tilt increased the maximal gain, the response range and the minimum value of SNA, the curves were almost superimposable in these SNAs regardless of postures. Scatter plotting of cardiac SNA over renal SNA during the stepwise changes in CSP was close to the line of identity in 0 degrees supine and 60 degrees upright tilt postures. In addition, upright tilt also shifted the reverse-sigmoidal curve of the CSP-heart rate relationship to a higher heart rate, with increases in the maximal gain and the response range. In conclusion, upright posture caused a resetting of arterial baroreflex control of SNA similarly in renal and cardiac SNAs in anesthetized rabbits.

In vivo direct monitoring of vagal acetylcholine release to the sinoatrial node

To directly monitor vagal acetylcholine (ACh) release into the sinoatrial node, which regulates heart rate, we implanted a microdialysis probe in the right atrium near the sinoatrial node and in the right ventricle of anesthetized rabbits, and perfused with Ringers solution containing eserine. (1) Electrical stimulation of right or left cervical vagal nerve decreased atrial rate and increased dialysate ACh concentration in the right atrium in a frequency-dependent manner. Compared to left vagal stimulation, right vagal nerve stimulation decreased atrial rate to a greater extent at all frequencies, and increased dialysate ACh concentration to a greater extent at 10 and 20 Hz. However, dialysate ACh concentration in the right atrium correlated well with atrial rate independent of whether electrical stimulation was applied to the right or left vagal nerve (atrial rate=304-131 x log[ACh], R(2)=0.77). (2) Right or left vagal nerve stimulation at 20 Hz decreased atrial rate and increased dialysate ACh concentrations in both the right atrium (right, 17.9+/-4.0 nM; left, 7.9+/-1.4 nM) and right ventricle (right, 0.9+/-0.3 nM; left, 1.0+/-0.4 nM). However, atrial dialysate ACh concentrations were significantly higher than ventricular concentrations, while ventricular dialysate ACh concentrations were not significantly different between right and left vagal nerve stimulation. (3) The response of ACh release to right and left vagal nerve stimulation was abolished by intravenous administration of a ganglionic blocker, hexamethonium bromide. In conclusion, ACh concentration in dialysate from the right atrium, sampled by microdialysis, is a good marker of ACh release from postganglionic vagal nerves to the sinoatrial node.

Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic‐denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP–SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA–AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP–AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.