Spleen reactivity during incremental ascent to altitude

Abstract

The spleen contains a reservoir of red blood cells that are mobilized into circulation when under physiological stress. Despite the spleen having an established role in compensation to acute hypoxia, no previous work has assessed the role of the spleen during ascent to high altitude. Twelve participants completed 2 min of handgrip exercise at 30% of maximal voluntary contraction at 1,045, 3,440, and 4,240 m. In a subset of eight participants, an infusion of phenylephrine hydrochloride was administered at a dosage of 30 µg/l of predicted blood volume at each altitude. The spleen was imaged by ultrasound via a 2- to 5.5-MHz curvilinear probe. Spleen volume was calculated by the prolate ellipsoid formula. Finger capillary blood samples were taken to measure hematocrit. Spleen images and hematocrit were taken both before and at the end of both handgrip and phenylephrine infusion. No changes in resting spleen volume were observed between altitudes. At low altitude, the spleen contracted in response to handgrip [272.8 ml (SD 102.3) vs. 249.6 ml (SD 105.7), P = 0.009], leading to an increase in hematocrit (42.6% (SD 3.3) vs. 44.3% (SD 3.3), P = 0.023] but did not contract or increase hematocrit at the high-altitude locations. Infusion of phenylephrine led to spleen contraction at all altitudes, but only lead to an increase in hematocrit at low altitude. These data reveal that the human spleen may not contribute to acclimatization to chronic hypoxia, contrary to its response to acute sympathoexcitation. These results are explained by alterations in spleen reactivity to increased sympathetic activation at altitude. NEW & NOTEWORTHY The present study demonstrated that, despite the known role of the human spleen in increasing oxygen delivery to tissues during acute hypoxia scenarios, the spleen does not mobilize red blood cells during ascent to high altitude. Furthermore, the spleen’s response to acute stressors at altitude depends on the nature of the stressor; the spleen’s sensitivity to neurotransmitter is maintained, while its reflex response to stress is dampened.

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea

“…In contrast, a recent investigation found that spleen size was unchanged throughout incremental ascent at HA, while injection of phenylephrine hydrochloride induced spleen contraction during ascent, but not hand grip exercise (Purdy et al., 2018). The authors concluded that the spleen does not contribute to the acclimatization process at HA.…”

Spleen contraction elevates hemoglobin concentration at high altitude during rest and exercise

“…The spleen is mainly innervated by sympathetic nerves with both α-and β-adrenoceptors (Ayers et al 1972) and spleen contraction can probably be induced by both neural input and catecholamine release (Stewart and McKenzie 2002). While resting spleen volumes observed by Purdy et al (2018) at 1045 m (273 mL), were similar to what we observed at 1370 m (252 mL), their handgrip exercise at 1045 m only caused a spleen contraction of 8%, while in our study, the step test caused a 21% spleen contraction. Likewise, the Hct in their study increased from baseline by 4%, while in our study, by 6%.…”

“…There could also be other vascular responses from injection of the phenylephrine bolus, e.g., overstimulation of the baroreceptors, which could have blunted the endogenous sympathetic activity. Therefore, we consider the study by Purdy et al (2018) inconclusive of whether spleen contraction occurs during exercise at high altitude. Their lack of effect of altitude on resting spleen volume remains contrasting to our observations.…”

“…Purdy et al (2018) thus suggested that the constant spleen volume at different altitudes is a result of a decreased reactivity to sympathetic activity but while there may be a long-term downregulation of beta-adrenoreceptors with chronic hypoxia (Richalet et al 1988), this may not likely have developed in these relatively un-acclimatized subjects. While both the studies by Richardson et al (2007) and Purdy et al (2018) may suggest that splenic reactivity was reduced at high altitude, the present study involving whole-body exercise induced a sufficient stressor to manifest as a powerful response also at high altitude. However, we suggest that the spleen response will likely reach a "roof" due to its anatomical properties, which appears to be the case at the highest altitudes.…”

Spleen Size and Function in Sherpa Living High, Sherpa Living Low and Nepalese Lowlanders

“…While hypoxia is identified as the main stimulus initiating spleen contraction, hypercapnia has a contributing role (Richardson et al, 2012). Spleen contraction is also initiated by intense exercise (Sandler et al, 1984;Laub et al, 1993) and is likely also initiated by general sympathetic activation (Frances et al, 2008;Purdy et al, 2018).…”