Effects of short-term mild hypercapnia during head-down tilt on intracranial pressure and ocular structures in healthy human subjects

Abstract

Many astronauts experience ocular structural and functional changes during long-duration spaceflight, including choroidal folds, optic disc edema, globe flattening, optic nerve sheath diameter (ONSD) distension, retinal nerve fiber layer thickening, and decreased visual acuity. The leading hypothesis suggests that weightlessness-induced cephalad fluid shifts increase intracranial pressure (ICP), which contributes to the ocular structural changes, but elevated ambient CO₂ levels on the International Space Station may also be a factor. We used the spaceflight analog of 6° head-down tilt (HDT) to investigate possible mechanisms for ocular changes in eight male subjects during three 1-h conditions: Seated, HDT, and HDT with 1% inspired CO₂ (HDT + CO₂). Noninvasive ICP, intraocular pressure (IOP), translaminar pressure difference (TLPD = IOP-ICP), cerebral and ocular ultrasound, and optical coherence tomography (OCT) scans of the macula and the optic disc were obtained. Analysis of one-carbon pathway genetics previously associated with spaceflight-induced ocular changes was conducted. Relative to Seated, IOP and ICP increased and TLPD decreased during HDT During HDT + CO₂ IOP increased relative to HDT, but there was no significant difference in TLPD between the HDT conditions. ONSD and subfoveal choroidal thickness increased during HDT relative to Seated, but there was no difference between HDT and HDT + CO₂ Visual acuity and ocular structures assessed with OCT imaging did not change across conditions. Genetic polymorphisms were associated with differences in IOP, ICP, and end-tidal PCO₂ In conclusion, acute exposure to mild hypercapnia during HDT did not augment cardiovascular outcomes, ICP, or TLPD relative to the HDT condition.

Keywords: NASA; Head‐down tilt; hypercapnia; one‐carbon metabolism; translaminar pressure difference.

Figure 1

Schematic of study protocol depicting (A) the timeline and order in which measurements were obtained during each condition and (B) the (i) Seated, (ii) HDT, and (iii) HDT + CO₂ conditions. IOP, intraocular pressure; OCT, optical coherence tomography; TCD, transcranial Doppler ultrasound; nICP, noninvasive measure of intracranial pressure; P_ETCO ₂, end‐tidal partial pressure of carbon dioxide.

Figure 2

(A) Inspired PCO ₂ (P_ICO ₂) and (B) end‐tidal PCO ₂ (P_ETCO ₂) for all subjects in each of the three conditions. Values are means ± 95% confidence intervals. *P < 0.05 versus Seated, ^†P < 0.05 versus HDT. n = 8 subjects for all variables.

Figure 3

(A) Central retinal artery blood flow velocity (CRA _vel) and (B) central retinal artery blood flow conductance index (CRAC _i) for all subjects in each of the three conditions. Values are means ± 95% confidence intervals. *P < 0.05 versus Seated. n = 8 subjects for all variables.

Figure 4

(A) Intraocular pressure (IOP), (B) noninvasive estimate of intracranial pressure (nICP), and (C) the resulting translaminar pressure difference (TLPD = IOP–nICP) for all subjects in each of the three conditions. Values are means ± 95% confidence intervals. *P < 0.05 versus Seated, ^†P < 0.05 versus HDT. n = 8 subjects for all variables.

Figure 5

(A) IOP, (B) nICP, and (C) TLPD for SNP+ (filled) and SNP− (open) groups during each condition. Values are means ± 95% confidence intervals. P‐value indicates group by condition interaction. n = 4 subjects in each SNP+ and SNP‐ groups.

Figure 6

(A) P_ETCO ₂ for SNP+ (filled) and SNP− (open) groups during each condition. (B) Change in MCA _vel compared to Seated for SNP+ (filled, n = 4) and SNP− (open, n = 4) groups during head‐down tilt (HDT) and HDT + CO ₂. (C) Change in MCA _vel as a function of the change in P_ETCO ₂ between Seated and HDT + CO ₂ for SNP+ (filled, n = 4) and SNP− (open, n = 4) groups. Linear regression slopes for the SNP+ (dashed, r²=0.7256) and SNP− (dotted, r² = 0.5077) groups were not significantly different.

Figure 7

P_ETCO ₂ during HDT + CO ₂ by MTRR 66 genotype. The subject indicated by the open circle had a B‐12 deficiency which could produce a similar phenotype as the GG subjects.

Figure 8

Optic nerve sheath diameter (ONSD) as a function of nICP during each condition for all eight subjects. Dashed lines represent linear regression of data for each subject.