scholarly journals Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex

2022 ◽  
Vol 12 ◽  
Author(s):  
Hironori Watanabe ◽  
Shotaro Saito ◽  
Takuro Washio ◽  
Damian Miles Bailey ◽  
Shigehiko Ogoh

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

2009 ◽  
Vol 106 (3) ◽  
pp. 880-886 ◽  
Author(s):  
Shigehiko Ogoh ◽  
Philip N. Ainslie ◽  
Tadayoshi Miyamoto

The respiratory and cerebrovascular reactivity to changes in arterial Pco2 ([Formula: see text]) is an important mechanism that maintains CO2 or pH homeostasis in the brain. It remains unclear, however, how cerebrovascular CO2 reactivity might influence the respiratory chemoreflex. The purpose of the present study was therefore to examine the interaction between onset responses of the respiratory chemoreflex and middle cerebral artery (MCA) mean blood velocity ( Vmean) to hypercapnia (5.0% CO2-40% O2-balance N2) at rest and during dynamic exercise (∼1.0 l/min O2 consumption). Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay ( t0)] and time constant (τ). At rest, t0 and τ data indicated that the MCA Vmean onset response was faster than the ventilatory (V̇e) response ( P < 0.001). In contrast, during exercise, t0 of V̇e and MCA Vmean onset responses were decreased. In addition, despite the enhanced [Formula: see text] response to CO2 administration ( P = 0.014), τ of MCA Vmean tended to increase during exercise ( P = 0.054), whereas τ of V̇e decreased ( P = 0.015). These findings indicate that 1) at rest, faster washout of CO2 via cerebral vasodilation results in a reduced activation of the central chemoreflex and subsequent reduced V̇e onset response, and 2) during exercise, despite higher rates of increasing [Formula: see text], the lack of change in the onset response of cerebral blood flow and reduced washout of CO2 may act to augment the V̇e onset response.


2007 ◽  
Vol 103 (2) ◽  
pp. 452-458 ◽  
Author(s):  
Don D. Sheriff ◽  
Inger-Helene Nådland ◽  
Karin Toska

Tolerance to +G z gravitational stress is reduced when +G z stress is preceded by exposure to hypogravity (fraction, 0, or negative G z). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G z stress (head-up tilt; HUT) when this stress is immediately preceded by −G z stress (head-down tilt; HDT). The aims of the present study were to characterize the hemodynamic consequences of brief HDT on subsequent HUT and to test the hypothesis that an elevation in leg vascular conductance induced by −G z stress contributes to the exaggerated fall in ELAP. Young healthy subjects ( n = 3 men and 4 women) were subjected to 30 s of 30° HUT from a horizontal position and to 30 s of 30° HUT when HUT was immediately preceded by 20 s of −15° HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced designed to minimize possible time effects of repeated exposure to gravitational stress. One minute was allowed for recovery between tilts. Brief exposure to HDT elicited an exaggerated fall in ELAP during the first seconds of the subsequent HUT (−17.9 ± 1.4 mmHg) compared with HUT alone (−12.4 ± 1.2 mmHg, P <0.05) despite a greater rise in stroke volume (Doppler ultrasound) and cardiac output over this brief time period in the HDT-HUT trials compared with the HUT trials (thereafter stroke volume fell under both conditions). The greater fall in ELAP was associated with an exaggerated increase in leg blood flow (femoral artery Doppler ultrasound) and was therefore largely (70%) attributable to an exaggerated rise in estimated leg vascular conductance, confirming our hypotheses. Thus brief exposure to −G z stress leads to an exaggerated fall in ELAP during subsequent HUT, owing to an exaggerated increase in estimated leg vascular conductance.


2010 ◽  
Vol 108 (3) ◽  
pp. 523-532 ◽  
Author(s):  
Don D. Sheriff ◽  
Inger Helene Nådland ◽  
Karin Toska

Tolerance to +G z gravitational stress is reduced when +G z stress is preceded by exposure to hypogravity (fractional, 0, or negative Gz). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G z stress (head-up tilt; HUT) when this stress is immediately preceded by −G z stress (head-down tilt; HDT), termed the “push-pull effect.” The aim of the present study was to test the hypothesis that sympathetic responses contribute to the push-pull effect. Young, healthy subjects ( n = 7 males and 3 females) were subjected to 30 s of 30° HUT from a horizontal position and to 30 s of 30° HUT when HUT was immediately preceded by 20 s of −15° HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced design, and 1 min was allowed for recovery between tilts. This protocol was repeated during clonidine administration (2.5 μg/kg bolus over 30 min and then continuously at 0.36 μg·kg−1·h−1). Clonidine blunted the vasomotor responses to tilting, and this led to exaggerated changes in arterial pressure. Clonidine exerted little specific influence on the push-pull effect. Thus sympathetic responses appear neither to contribute to, nor protect against, the push-pull effect for the rate and duration of tilting imposed in the present study.


2010 ◽  
pp. 43-51
Author(s):  
G Raffai ◽  
C Csekő ◽  
G Nádasy ◽  
E Monos

Sustained orthostasis elicits the elevation of arterial blood pressure (BP) via sympathetic activation in conscious Wistar rats for at least 2 hours. We tested the hypothesis whether vestibular apparatus plays a role in BP and heart rate (HR) control in response to prolonged gravitational stress. BP and HR responses to 45º head-up for either 2 or 24 hours were monitored by telemetry. Vestibular lesions (VL) were performed by a modified microsurgical-chemical technique. Horizontal BP and HR were not influenced by VL preceding 2-hour tilt. VL abolished the sustained 2-hour BP response to head-up tilt (8.3±0.9 mm Hg relative to horizontal values) while suppressed HR transiently only. VL eliminated diurnal BP fluctuations and decreased HR in horizontal position for 24 hours. Head-up tilt for 24 hours increased BP and HR progressively in intact animals, raising their daily average value by 5.6±0.7 mm Hg and 22.2±6 BPM, respectively. VL resulted in an initial BP rise followed by progressive BP reduction in response to long-term head-up tilt (4±2.2 mm Hg) without eliminating the tachycardia (34.4±5.4 BPM). Thus, blockade of labyrinthine inputs attenuates the BP responses elicited by both intermediate and long-term gravitational stress of orthostatic type. However, other sensory inputs derived from non-vestibular cues (e.g. proprioceptive, visual, visceral, cutaneous etc.) seem to be effective enough to maintain BP normal.


2003 ◽  
Vol 95 (1) ◽  
pp. 159-166 ◽  
Author(s):  
Amy L. Hakeman ◽  
Jami L. Shepard ◽  
Don D. Sheriff

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the “push-pull effect.” The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90° head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90° head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 ± 1.3, -23 ± 0.7, and -28 ± 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences ( P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.


Author(s):  
Lonnie G. Petersen ◽  
Richard Stuart Whittle ◽  
Justin Hyunwoo Lee ◽  
Jeremy Sieker ◽  
Joseph Carlson ◽  
...  

Changes in the gravitational vector by postural changes or weightlessness induce fluid shifts impacting ocular hemodynamics and regional pressures. This investigation explores the impact of changes in direction of the gravitational vector on intraocular pressure (IOP), mean arterial pressure at eyelevel (MAPeye), and ocular perfusion pressure (OPP), which is critical for ocular health. Thirteen subjects underwent 360° of tilt (including both prone and supine positions) at 15º increments. At each angle, steady-state IOP and MAPeye were measured and OPP calculated as MAPeye-IOP. Experimental data were compared to a 6-compartment lumped parameter model of the eye. Mean IOP, MAPeye, and OPP significantly increased from 0º supine to 90º head down tilt (HDT) by 20.7±1.7 mmHg (ᵅD; < 0.001), 38.5±4.1 mmHg (ᵅD; < 0.001), and 17.4±3.2 mmHg (ᵅD; <0.001), respectively. Head up tilt (HUT) significantly decreased OPP by 16.5±2.5 mmHg (ᵅD; < 0.001). IOP was significantly higher in prone vs. supine position for much of the tilt range. Our study indicates that OPP is highly gravitationally dependent. Specifically, data show that MAPeye is more gravitationally dependent than IOP, thus causing OPP to increase during HDT and to decrease during HUT. Additionally, IOP was elevated in prone position compared to supine position due to the additional hydrostatic column between the base of the rostral globe to the mid-caudal plane, supporting the notion that hydrostatic forces play an important role in ocular hemodynamics. Changes in OPP as a function of changes in gravitational stress and/or weightlessness may play a role in the pathogenesis of spaceflight-associated neuro-ocular syndrome.


1994 ◽  
Vol 77 (5) ◽  
pp. 2426-2433 ◽  
Author(s):  
R. K. Puri ◽  
S. S. Segal

We investigated microvascular responses to head-up tilt (HUT) and head-down tilt (HDT) in striated muscle of conscious male rats (n = 15; body wt 163 +/- 5 g). To observe the microcirculation in the cutaneous maximus muscle, a transparent polycarbonate chamber (1.5 cm diam) was implanted aseptically into a skin fold created between the shoulders. Rats were trained to sit quietly during HUT and HDT while positioned on a horizontal microscope that rotated in the sagittal plane. At 4–5 days after surgery, arteriole and venule diameters were recorded using videomicroscopy while the rat experienced 10 min each (in random order) of HUT or HDT at 20 degrees or 40 degrees separated by 2-h rest periods. HUT had no affect on microvessel diameter; 20 degrees HDT had little affect. In response to 40 degrees HDT, “large” arterioles (88 +/- 18 microns; n = 10) constricted by 18 +/- 2% (P < 0.05) and “small” arterioles (40 +/- 17 microns; n = 7) dilated by 21 +/- 3% (P < 0.05); this difference suggests variation in mechanisms controlling arteriolar responses. Venules (45 +/- 22 microns; n = 9) exhibited a larger fluctuation in diameter (amplitude 13 +/- 5 microns) during 40 degrees HDT compared with other body positions (amplitude typically 2–3 microns), suggesting that venomotor activity may be induced with sufficient fluid shift or change in central venous pressure. These observations illustrate a viable model for studying microvascular responses to gravitational stress in conscious rats.


Author(s):  
K Alhadid ◽  
M Kirby-Allen ◽  
G DeVeber ◽  
W Logan ◽  
N Dlamini

Background: A diagnosis of SCD in childhood confers a 200-fold increase in the risk of arterial ischemic stroke. Blood flow velocity measures provide better identification of ischemic risk compared to angiography. This indicates that steno-occlusive arteriopathy is not the singular causative factor. Cerebrovascular reactivity allows for augmentation of cerebral blood flow when needed. Kosinski et al in 2016 demonstrated a direct correlation between CVR and hematocrit levels in SCD. We report a case where CVR persistently normalized in an SCD patient following bone marrow transplant therapy (BMT). Methods: A nine-month-old SCD patient presented with right AIS. Angiography revealed a bilateral Moya-Moya like arteriopathy. A TCD study was normal while a CVR-MRI study revealed markedly impaired reactivity in the entire anterior circulation. Haemaglobin-S at that time was 20.2 %. BMT was performed at age four due to frequent sickle cell crises. Results: One year post-transplant, CVR had dramatically improved in areas previously shown to have impairment (haemoglobin-S 0%). Neuroimaging five years post-transplant showed no further arteriopathy and persistently normalized CVR. Conclusions: BMT therapy resulted in the arrest of progressive intracranial arteriopathy and persistently restored vascular reserve. SCD might not only produce global hematological effects but also triggers local processes such as endothelial dysfunction and vascular inflammation that impair cerebrovascular function.


Sign in / Sign up

Export Citation Format

Share Document