Ryo Yanagida

Subfoveal choroidal thickness and foveal retinal thickness during head-down tilt.

INTRODUCTION To reveal subtle morphological changes in the eye during simulated microgravity for spaceflights, we measured subfoveal choroidal thickness and foveal retinal thickness during 10 degrees head-down tilt (HDT). We hypothesized that elevated ophthalmic vein pressure during simulated microgravity increases subfoveal choroidal thickness via enlargement of the choroidal vasculature and greater choroidal blood volume. METHODS The right eyes of nine healthy subjects (seven men, two women) were examined. Subfoveal choroidal thickness and foveal retinal thickness were measured using spectral domain-optical coherence tomography in the sitting position, and after 15 and 30 min of 10 degrees HDT. Intraocular pressure was also measured. RESULTS Mean subfoveal choroidal thickness (+/- SEM) increased from 300 +/- 31 microm in the sitting position to 315 +/- 31 microm with 15-min HDT, and 333 +/- 31 microm with 30-min HDT. However, no change in foveal retinal thickness was observed (228 +/- 9 microm in the sitting position, 228 +/- 10 microm with 15-min HDT and 228 +/- 9 microm with 30-min HDT). Intraocular pressure increased from 14 +/- 1 mmHg in the sitting position to 21 +/- 2 mmHg with 30-min HDT (54 +/- 6%, N = 5). DISCUSSION Subfoveal choroidal thickness and intraocular pressure were increased by HDT during simulated microgravity, although no change in foveal retinal thickness was observed.

Cerebral circulation during mild +Gz hypergravity by short-arm human centrifuge

We examined changes in cerebral circulation in 15 healthy men during exposure to mild +Gz hypergravity (1.5 Gz, head-to-foot) using a short-arm centrifuge. Continuous arterial pressure waveform (tonometry), cerebral blood flow (CBF) velocity in the middle cerebral artery (transcranial Doppler ultrasonography), and partial pressure of end-tidal carbon dioxide (ETco(2)) were measured in the sitting position (1 Gz) and during 21 min of exposure to mild hypergravity (1.5 Gz). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial pressure (MAP) and mean CBF velocity (MCBFV). Steady-state MAP did not change, but MCBFV was significantly reduced with 1.5 Gz (-7%). ETco(2) was also reduced (-12%). Variability of MAP increased significantly with 1.5 Gz in low (53%)- and high-frequency ranges (88%), but variability of MCBFV did not change in these frequency ranges, resulting in significant decreases in transfer function gain between MAP and MCBFV (gain in low-frequency range, -17%; gain in high-frequency range, -13%). In contrast, all of these indexes in the very low-frequency range were unchanged. Transfer from arterial pressure oscillations to CBF fluctuations was thus suppressed in low- and high-frequency ranges. These results suggest that steady-state global CBF was reduced, but dynamic cerebral autoregulation in low- and high-frequency ranges was improved with stabilization of CBF fluctuations despite increases in arterial pressure oscillations during mild +Gz hypergravity. We speculate that this improvement in dynamic cerebral autoregulation within these frequency ranges may have been due to compensatory effects against the reduction in steady-state global CBF.

The Effects of Flumazenil After Midazolam Sedation on Cerebral Blood Flow and Dynamic Cerebral Autoregulation in Healthy Young Males.

Background: It is unknown whether flumazenil antagonizes the decrease in cerebral blood flow or the alteration in dynamic cerebral autoregulation induced by midazolam. We, therefore, investigated the effects on cerebral circulation of flumazenil administered after midazolam, to test our hypothesis that, along with complete reversal of sedation, flumazenil antagonizes the alterations in cerebral circulation induced by midazolam. Methods: Sixteen healthy young male subjects received midazolam followed by flumazenil. The modified Observer’s Assessment of Alertness/Sedation (OAA/S) scale and bispectral index (BIS) were used to assess levels of sedation/awareness. For evaluation of cerebral circulation, steady-state mean cerebral blood flow velocity (MCBFV) was measured by transcranial Doppler ultrasonography. In addition, dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between mean arterial pressure (MAP) variability and MCBFV variability. Results: During midazolam sedation, defined by an OAA/S score of 3 (responds only after name is called loudly and/or repeatedly), BIS, steady-state MAP, steady-state CBFV, and transfer function gain decreased significantly compared with baseline. After flumazenil administration, an OAA/S score of 5 (responds readily to name spoken in a normal tone) was confirmed. Then, BIS and MAP returned to the same level as baseline. However, steady-state MCBFV showed a further significant decrease compared with that under midazolam sedation, and the decreased transfer function gain persisted. Conclusions: Contrary to our hypothesis, the present results suggest that despite complete antagonism of the sedative effects of midazolam, flumazenil would not reverse the alterations in cerebral circulation induced by midazolam.

Sustained mild hypergravity reduces spontaneous cardiac baroreflex sensitivity

Head-to-foot gravitational force >1G (+Gz hypergravity) augments venous pooling in the lower body and reduces central blood volume during exposure, compared with 1Gz. Central hypovolemia has been reported to reduce spontaneous cardiac baroreflex sensitivity. However, no investigations have examined spontaneous cardiac baroreflex sensitivity during exposure to sustained mild +Gz hypergravity. We therefore hypothesized that mild +Gz hypergravity would reduce spontaneous cardiac baroreflex sensitivity, compared with 1Gz. To test this hypothesis, we examined spontaneous cardiac baroreflex sensitivity in 16 healthy men during exposure to mild +Gz hypergravity using a short-arm centrifuge. Beat-to-beat arterial blood pressure (tonometry) and R-R interval (electrocardiography) were obtained during 1Gz and 1.5Gz exposures. Spontaneous cardiac baroreflex sensitivity was assessed by sequence slope and transfer function gain. Stroke volume was calculated from the arterial pressure waveform using a three-element model. All indices of spontaneous cardiac baroreflex sensitivity decreased significantly (up slope: 18.6±2.3→12.7±1.6ms/mmHg, P<0.001; down slope: 19.0±2.5→13.2±1.3ms/mmHg, P=0.002; transfer function gain in low frequency: 14.4±2.2→10.1±1.1ms/mmHg, P=0.004; transfer function gain in high frequency: 22.2±7.5→12.4±3.5ms/mmHg, P<0.001). Stroke volume decreased significantly (88±5→80±6ml, P=0.025). Moreover, although systolic arterial pressure variability increased, R-R interval variability did not increase. These results suggest that even mild +Gz hypergravity reduces spontaneous cardiac baroreflex sensitivity, increasing the risk of cardiovascular disturbance during the exposure.

Dose-Effect Relationship Between Mild Levels of Hypergravity and Autonomic Circulatory Regulation.

INTRODUCTION The dose-effect relationships between different levels of hypergravity (>+1.0 Gz) and steady-state hemodynamic parameters have been reported in several studies. However, little has been reported on the dose-effect relationship between hypergravity levels and estimates of autonomic circulatory regulation, such as heart rate variability, arterial pressure variability, and spontaneous cardiac baroreflex sensitivity. We investigated dose-effect relationships between hypergravity levels from +1.0 Gz to +2.0 Gz (Δ0.5 Gz) and autonomic circulatory regulation to test our hypothesis that autonomic circulatory regulation has a linear relationship with hypergravity levels. METHODS Using a short-arm human centrifuge, 10 healthy seated men were subjected to +1.0 Gz, +1.5 Gz, and +2.0 Gz hypergravity. We evaluated steady-state hemodynamic parameters and autonomic circulatory regulation indices. Heart rate variability, arterial pressure variability, and spontaneous cardiac baroreflex sensitivity between arterial pressure and R-R interval variabilities were assessed by spectral analysis, sequence analysis, and transfer function analysis. RESULTS Steady-state heart rate, stroke volume, and sequence slope (indicating spontaneous cardiac baroreflex sensitivity in response to rapid changes in arterial pressure) showed linear correlations with increases in gravity (from +1.0 Gz to +2.0 Gz). On the other hand, steady-state cardiac output, steady-state systolic arterial pressure, and low-frequency power of diastolic arterial pressure (indicating peripheral vasomotor sympathetic activity) remained unchanged with gravity increases. CONCLUSION Contrary to our hypothesis, the present study suggested that autonomic circulatory regulations show complex changes with hypergravity levels. Spontaneous cardiac baroreflex sensitivity reduces in a dose-dependent manner from +1.0 Gz to +2.0 Gz, whereas peripheral vasomotor sympathetic activity seems to be maintained.

The Effect of the Dexmedetomidine Loading dose on Arterial-Cardiac Baroreflex

要旨 デクスメデトミジンの初期負荷投与では,血圧 上昇と心拍数減少が認められるため,循環調節機能のひ とつである動脈圧受容器心臓反射にも変化が生じている 可能性がある.そこで,デクスメデトミジンの初期負荷 投与が動脈圧受容器心臓反射に及ぼす影響を検討するこ とを目的に過去の実験データの再解析を行った. 健康成人男性 12名を対象とし,デクスメデトミジン を 6 μg/kg/hで 10分間投与した.投与前と投与中に,一 心拍毎の収縮期血圧と R-R間隔を記録し,シークエン ス法を用いて両者の関係から動脈圧受容器心臓反射機能 の評価指標である Total-slope (ms/mmHg) を算出・評価 した. 投与前と比較して投与中では,収縮期,拡張期血圧共 に有意に上昇し,心拍数は有意に減少した.その際, Total-slopeは有意に増加した. 本研究より,デクスメデトミジンの初期負荷投与は動 脈圧受容器心臓反射機能を増強することが示唆された.

Dynamic cerebral autoregulation during the combination of mild hypercapnia and cephalad fluid shift

BACKGROUND Mild hypercapnia combined with a cephalad fluid shift [e.g., that occurring during spaceflight or laparoscopic surgery with head-down tilt (HDT)] might affect cerebral autoregulation. However, no reports have described the effects of the combination on dynamic cerebral autoregulation. Therefore, we tested the hypothesis that the combination of mild hypercapnia and a cephalad fluid shift would attenuate dynamic cerebral autoregulation. METHODS There were 15 healthy male volunteers who were exposed to 4 10-min protocols in which they received air in the supine position (Placebo/Supine), 3% carbon dioxide (CO2) in the supine position (CO2/Supine), air with -10° HDT (Placebo/HDT) and 3% CO2 with -10° HDT (CO2/HDT). Dynamic cerebral autoregulation was evaluated using a transfer function analysis of the beat-to-beat variability in mean arterial blood pressure (ABP) and mean cerebral blood flow (CBF) velocity. RESULTS The phase in the low-frequency range was significantly lower during CO2/HDT than all other protocols, where CO2/HDT was -25% lower than Placebo/Supine (CO2/HDT, 0.49 ± 0.21; Placebo/Supine, 0.65 ± 0.16 radians). The transfer function gain in the low-frequency range was significantly higher during CO2/HDT than all other protocols, where CO2/HDT was 26% higher than Placebo/Supine (CO2/HDT, 1.08 ± 0.34; Placebo/Supine, 0.86 ± 0.28 cm · s-1 · mmHg-1). However, neither the CO2/Supine nor Placebo/HDT showed significant differences compared with the Placebo/Supine. DISCUSSION Even short-term exposure to 3% CO2 plus HDT increased synchrony and the magnitude of transmission between ABP and CBF in the low-frequency range. Thus, the combination of mild hypercapnia and a cephalad fluid shift attenuated dynamic cerebral autoregulation.Kurazumi T, Ogawa Y, Yanagida R, Morisaki H, Iwasaki K. Dynamic cerebral autoregulation during the combination of mild hypercapnia and cephalad fluid shift. Aerosp Med Hum Perform. 2017; 88(9):819-826.