INFLAMMATORY CYTOKINES ASSOCIATED WITH BLUNTED HYPOXIC PULMONARY VASOCONSTRICTION IN APNEA DIVERS

Authors

T Kelly
K DiMarco
C Brown
M Bryant-Ekstrand
R Lord
T Dawkins
A Drane
JE Futral
O Barak
T Dragun
M Stembridge
B Spajic
I Drvis
JW Duke
PN Ainslie
GE Foster
Z Dujic
AT Lovering

Abstract

T. Kelly¹, K. DiMarco¹, Courtney Brown², Mohini Bryant-Ekstrand¹, Rachel Lord³, Tony Dawkins³, Aimee Drane³, Joel E. Futral¹, Otto Barak⁴, Tanja Dragun⁵, Michael Stembridge³, Boris Spajić⁶, Ivan Drviš⁶, Joseph W. Duke⁷, Philip N. Ainslie², Glen E. Foster², Zeljko Dujic⁵, & A.T. Lovering¹

¹University of Oregon, Department of Human Physiology, Eugene OR, USA; ²University of British Columbia, Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, Kelowna, BC, Canada; ³Cardiff Metropolitan University, School of Sport and Health Sciences, Cardiff, Wales, UK; ⁴University of Novi Sad, Department of Physiology, Novi Sad, Serbia; ⁵University of Split School of Medicine, Department of Integrative Physiology, Split, Croatia; ⁶University of Zagreb, Faculty of Kinesiology, Zagreb, Croatia; ⁷Northern Arizona University, Department of Biological Sciences, Flagstaff, AZ, USA

PURPOSE: Our lab has previously reported blunted hypoxic pulmonary vasoconstriction in apnea divers (Kelly et al, Exp Physiol 2022). Why this occurs remains speculative but may relate to interactions between inflammatory cytokines and nitric oxide availability. We hypothesized that in apnea divers there would be a positive correlation between levels of inflammatory cytokines and degree of hypoxic pulmonary vasoconstriction. METHODS: 16 (4 women) apnea divers and 16 (4 women) non-diving age and sex-matched controls were recruited from diving camps in and around Split, Croatia and Eugene, Oregon. Serum was collected from each participant, then transthoracic ultrasound measures were made to calculate cardiac output (Q_T) and pulmonary artery systolic pressure (PASP). Total pulmonary resistance (TPR) was calculated as PASP/Q_T and converted to dynes/sec/cm^-5. After baseline ultrasound measures, participants breathed on a dynamic end-tidal forcing machine targeting an end-tidal O₂ ~50mmHg (corresponding to O₂ saturation of ~80%) while clamping end-tidal CO₂ at baseline value (~40mmHg). Ultrasound measures were repeated after 20 to 30-minutes of hypoxic breathing. ΔTPR was calculated as the change in TPR from baseline to the end of the hypoxic challenge. Serum was analyzed for cytokines using a flow cytometry bead-based multiplex assay. RESULTS: Data were analyzed by Pearson correlation. In apnea divers there were significant correlations between ΔTPR and levels of IL-8 (r = -.8151, r² = .6644, p = .0481), IFN-a2 (r = -.8344, r² = .6962, p = .0052), and IL-12p70 (r = -.9209, r² = .8481, p = .0264). There were no significant correlations in Controls. CONCLUSION: We report strong negative correlations between ΔTPR in response to a 20 to 30-minute hypoxic challenge and several inflammatory cytokines. Our results suggest that apnea divers may have an altered inflammatory cytokine profile which is related to reduced hypoxic pulmonary vasoconstriction.

US Fulbright Scholar’s Program # PS00273429, Burroughs Wellcome Fund # 1018799

Recommended Citation

Kelly, T; DiMarco, K; Brown, C; Bryant-Ekstrand, M; Lord, R; Dawkins, T; Drane, A; Futral, JE; Barak, O; Dragun, T; Stembridge, M; Spajic, B; Drvis, I; Duke, JW; Ainslie, PN; Foster, GE; Dujic, Z; and Lovering, AT (2023) "INFLAMMATORY CYTOKINES ASSOCIATED WITH BLUNTED HYPOXIC PULMONARY VASOCONSTRICTION IN APNEA DIVERS," International Journal of Exercise Science: Conference Proceedings: Vol. 8: Iss. 11, Article 57.
Available at: https://digitalcommons.wku.edu/ijesab/vol8/iss11/57