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Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Research Article

Varicocele at High Altitude; Venous Outflow Restriction by Hypobaric Hypoxia

Author(s): Diana Alcántara-Zapata, Carolina Nazzal, Sergio Muñoz, Nicole De Gregorio, Nella Marchetti and Claus Behn*

Volume 20, Issue 3, 2022

Published on: 13 July, 2022

Page: [303 - 309] Pages: 7

DOI: 10.2174/1570161120666220510120831

Price: $65

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Abstract

Background: Testicular aches have been reported to occur on exposure to high altitude (HA). As a painful expression of venous congestion at the pampiniform plexus, varicocele (VC) might be a consequence of cardiovascular adjustments at HA. Chile’s National Social Security Regulatory Body (SUSESO) emphasized evaluating this condition in the running follow-up study “Health effects of exposure to chronic intermittent hypoxia in Chilean mining workers.”

Objectives: This study aimed at investigating the prevalence of VC in a population usually shifting between sea level and HA, thereby intermittently being exposed to hypobaric hypoxia.

Methodology: Miners (n=492) agreed to be examined at their working place by a physician, in the context of a general health survey, for the presence of palpable VC, either visible or not. Among them was a group exposed to low altitude (LA) <2,400 m; n=123; another one exposed to moderate high altitude (MHA) working 3,050 m; n=70, and a third one exposed to very high altitude (VHA) >3,900 m, n=165. The Chi2 test and Kruskal-Wallis test were used for the descriptive analyses, and logistic regression was applied to evaluate the association of VC with exposure to HA. The Ethics Committee for Research in Human Beings, Faculty of Medicine, University of Chile, approved this project.

Results: VC prevalence (grades 2 and 3) was found to be 10% at LA, 4.1% at MHA, and 16.7% at VHA (p≤0.05). Hemoglobin oxygen saturation (SaO2) was lower, and hemoglobin concentrations were higher in workers with high-grade VC at VHA compared to LA and MHA (Wilcoxon tests, p<0.001). Odds ratios (OR) for the association of VC with HA were 3.7 (95%CI: 1.26 to 12.3) and 4.06 (95%CI: 1.73 to 11.2) for MHA and VHA, respectively.

Conclusion: Association of VC with HA, a clinically relevant finding, may be related to blood volume centralization mediated by hypobaric hypoxia.

Keywords: Varicocele, high altitude, hypobaric, hypoxia, venous, outflow, varicocele.

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[1]
Mallet R, Burtscher J, Richalet J, Millet G, Burtscher M. Impact of high altitude on cardiovascula health: Current perspectives. Vasc Health Risk Manag 2021; 31: 7-335.
[2]
Reyes JG, Farias JG, Henríquez-Olavarrieta S, et al. The hypoxic testicle: Physiology and pathophysiology. Oxid Med Cell Longev 2012; 2012: 929285.
[http://dx.doi.org/10.1155/2012/929285] [PMID: 23056665]
[3]
Herrera EA, Farías JG, Ebensperger G, Reyes RV, Llanos AJ, Castillo RL. Pharmacological approaches in either intermittent or permanent hypoxia: A tale of two exposures. Pharmacol Res 2015; 101: 94-101.
[http://dx.doi.org/10.1016/j.phrs.2015.07.011] [PMID: 26215469]
[4]
Shaw DM, Cabre G, Gant N. Hypoxic hypoxia and brain function in military aviation: Basic physiology and applied perspectives. Front Physiol 2021; 12: 665821.
[http://dx.doi.org/10.3389/fphys.2021.665821] [PMID: 34093227]
[5]
Grant I, Giussani D, Aiken C. Fetal growth and spontaneous preterm birth in high-altitude pregnancy: A systematic review, meta-analysis, and meta-regression. Int J Gynaecol Obs 2021.
[6]
Bomhard EM, Gelbke HP. Hypoxaemia affects male reproduction: A case study of how to differentiate between primary and secondary hy-poxic testicular toxicity due to chemical exposure. Arch Toxicol 2013; 87(7): 1201-18.
[http://dx.doi.org/10.1007/s00204-013-1024-6] [PMID: 23430139]
[7]
Paick S, Choi WS. Varicocele and testicular pain: A review. World J Mens Health 2019; 37(1): 4-11.
[http://dx.doi.org/10.5534/wjmh.170010] [PMID: 29774668]
[8]
Leslie S, Sajjad H, Siref L. Varicocele., Feb 14. StatPearls. Treasure 2021; I: 2021.
[9]
Zhu SM, Rao T, Yang X, et al. Autophagy may play an important role in varicocele. Mol Med Rep 2017; 16(4): 5471-9.
[http://dx.doi.org/10.3892/mmr.2017.7253] [PMID: 28849201]
[10]
Kang C, Punjani N, Lee R, Li P, Goldstein M. Goldstein, Effect of varicoceles on spermatogenesis. Semin Cell Dev Biol 2021; S1084-9521: 00078-1.
[11]
Gat Y, Joshua S, Vuk-Pavlović S, Goren M. Paying the price for standing tall: Fluid mechanics of prostate pathology. Prostate 2020; 80(15): 1297-303.
[http://dx.doi.org/10.1002/pros.24051] [PMID: 32833288]
[12]
Rizzoto G, Hall C, Tyberg JV, Thundathil JC, Caulkett NA, Kastelic JP. Increased testicular blood flow maintains oxygen delivery and avoids testicular hypoxia in response to reduced oxygen content in inspired air. Sci Rep 2018; 8(1): 10905.
[http://dx.doi.org/10.1038/s41598-018-29248-2] [PMID: 30026599]
[13]
Willie CK, MacLeod DB, Smith KJ, et al. The contribution of arterial blood gases in cerebral blood flow regulation and fuel utilization in man at high altitude. J Cereb Blood Flow Metab 2015; 35(5): 873-81.
[http://dx.doi.org/10.1038/jcbfm.2015.4] [PMID: 25690474]
[14]
Coles JP, Minhas PS, Fryer TD, et al. Effect of hyperventilation on cerebral blood flow in traumatic head injury: Clinical relevance and moni-toring correlates. Crit Care Med 2002; 30(9): 1950-9.
[http://dx.doi.org/10.1097/00003246-200209000-00002] [PMID: 12352026]
[15]
Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head injury: Effect on ischemic burden and cerebral oxidative metabo-lism. Crit Care Med 2007; 35(2): 568-78.
[http://dx.doi.org/10.1097/01.CCM.0000254066.37187.88] [PMID: 17205016]
[16]
Morel J, Gergelé L, Dominé A, et al. The venous-arterial difference in CO2 should be interpreted with caution in case of respiratory alkalosis in healthy volunteers. J Clin Monit Comput 2017; 31(4): 701-7.
[http://dx.doi.org/10.1007/s10877-016-9897-6] [PMID: 27287759]
[17]
Shahidi AM, Patel SR, Huang D, Tan O, Flanagan JG, Hudson C. Assessment of total retinal blood flow using Doppler Fourier Domain Opti-cal Coherence Tomography during systemic hypercapnia and hypocapnia. Physiol Rep 2014; 2(7): e12046.
[http://dx.doi.org/10.14814/phy2.12046] [PMID: 25038117]
[18]
Kety S, Schmidt C. The effects of active and passive hyperventiiation on cerebral blood flow, cerebral oxygen consumption, cardiac output, and blood pressure of normal young men. J Clin Invest 1946; 25(1): 107-19.
[http://dx.doi.org/10.1172/JCI101680]
[19]
Crystal GJ. Carbon dioxide and the heart: Physiology and clinical implications. Anesth Analg 2015; 121(3): 610-23.
[http://dx.doi.org/10.1213/ANE.0000000000000820] [PMID: 26287294]
[20]
Imray C, Chan C, Stubbings A, et al. Time course variations in the mechanisms by which cerebral oxygen delivery is maintained on exposure to hypoxia/altitude. High Alt Med Biol 2014; 15(1): 21-7.
[http://dx.doi.org/10.1089/ham.2013.1079] [PMID: 24559404]
[21]
Imray C. Lessons from altitude: Cerebral perfusion insights and their potential translational clinical significance. Exp Physiol 2016; 101(9): 1167-72.
[http://dx.doi.org/10.1113/EP085813] [PMID: 27061345]
[22]
Maggiorini M, Müller A, Hofstetter D, Bärtsch P, Oelz O. Assessment of acute mountain sickness by different score protocols in the Swiss Alps. Aviat Space Environ Med 1998; 69(12): 1186-92.
[PMID: 9856545]
[23]
Dellasanta P, Gaillard S, Loutan L, Kayser B. Comparing questionnaires for the assessment of acute mountain sickness. High Alt Med Biol 2007; 8(3): 184-91.
[http://dx.doi.org/10.1089/ham.2007.8305] [PMID: 17824818]
[24]
Mairer K, Wille M, Bucher T, Burtscher M. Prevalence of acute mountain sickness in the Eastern Alps. High Alt Med Biol 2009; 10(3): 239-45.
[http://dx.doi.org/10.1089/ham.2008.1091] [PMID: 19775213]
[25]
Tucker TW. A physics link between venous stenosis and multiple sclerosis. Med Hypotheses 2011; 77(6): 1074-8.
[http://dx.doi.org/10.1016/j.mehy.2011.09.006] [PMID: 21958625]
[26]
Lüddecke R, Lindner T, Forstenpointner J, Baron R, Jansen O, Gierthmühlen J. Should you stop wearing neckties?-wearing a tight necktie reduces cerebral blood flow. Neuroradiology 2018; 60(8): 861-4.
[http://dx.doi.org/10.1007/s00234-018-2048-7] [PMID: 29961088]
[27]
Teng C, Gurses-Ozden R, Liebmann JM, Tello C, Ritch R. Effect of a tight necktie on intraocular pressure. Br J Ophthalmol 2003; 87(8): 946-8.
[http://dx.doi.org/10.1136/bjo.87.8.946] [PMID: 12881330]
[28]
Bower EA, O’Donnell CP. Mean circulatory filling pressure during splanchnic nerve stimulation and whole-body hypoxia in the anaesthe-tized cat. J Physiol 1991; 432(1): 543-56.
[http://dx.doi.org/10.1113/jphysiol.1991.sp018399] [PMID: 1886068]
[29]
Bruno RM, Ghiadoni L, Seravalle G, Dell’oro R, Taddei S, Grassi G. Sympathetic regulation of vascular function in health and disease. Front Physiol 2012; 3: 284.
[http://dx.doi.org/10.3389/fphys.2012.00284] [PMID: 22934037]
[30]
Saito M, Mano T, Iwase S, Koga K, Abe H, Yamazaki Y. Responses in muscle sympathetic activity to acute hypoxia in humans. J Appl Physiol 1988; 65(4): 1548-52.
[http://dx.doi.org/10.1152/jappl.1988.65.4.1548] [PMID: 3182518]
[31]
Duplain H, Vollenweider L, Delabays A, Nicod P, Bärtsch P, Scherrer U. Augmented sympathetic activation during short-term hypoxia and high-altitude exposure in subjects susceptible to high-altitude pulmonary edema. Circulation 1999; 99(13): 1713-8.
[http://dx.doi.org/10.1161/01.CIR.99.13.1713] [PMID: 10190881]
[32]
Xie A, Skatrud JB, Puleo DS, Morgan BJ. Exposure to hypoxia produces long-lasting sympathetic activation in humans. J Appl Physiol 2001; 91(4): 1555-62.
[http://dx.doi.org/10.1152/jappl.2001.91.4.1555] [PMID: 11568136]
[33]
Lundby C, Calbet J, van Hall G, Saltin B, Sander M. Sustained sympathetic activity in altitude acclimatizing lowlanders and high-altitude na-tives. Scand J Med Sci Sports 2018; 28(3): 854-61.
[http://dx.doi.org/10.1111/sms.12976] [PMID: 28948697]
[34]
Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol 2003; 546(Pt 3): 921-9.
[http://dx.doi.org/10.1113/jphysiol.2002.031765] [PMID: 12563015]
[35]
Richalet J. Review article. Adv Exp Med Biol 2016; 903: 343-56.
[http://dx.doi.org/10.1007/978-1-4899-7678-9_23] [PMID: 27343107]
[36]
Cruz JC, Grover RF, Reeves JT, Maher JT, Cymerman A, Denniston JC. Sustained venoconstriction in man supplemented with CO2 at high altitude. J Appl Physiol 1976; 40(1): 96-100.
[http://dx.doi.org/10.1152/jappl.1976.40.1.96] [PMID: 1248989]
[37]
Jiang T, Steinberg SF. Beta 2-adrenergic receptors enhance contractility by stimulating HCO3(-)-dependent intracellular alkalinization. Am J Physiol 1997; 273(2 Pt 2): H1044-7.
[PMID: 9277526]
[38]
Morganti A, Giussani M, Sala C, et al. Effects of exposure to high altitude on plasma endothelin-1 levels in normal subjects. J Hypertens 1995; 13(8): 859-65.
[http://dx.doi.org/10.1097/00004872-199508000-00006] [PMID: 8557963]
[39]
Goerre S, Wenk M, Bärtsch P, et al. Endothelin-1 in pulmonary hypertension associated with high-altitude exposure. Circulation 1995; 91(2): 359-64.
[http://dx.doi.org/10.1161/01.CIR.91.2.359] [PMID: 7805238]
[40]
Lackermair K, Schuhmann CG, Mertsch P, Götschke J, Milger K, Brunner S. Effect of acute altitude exposure on serum markers of platelet activation. High Alt Med Biol 2019; 20(3): 318-21.
[http://dx.doi.org/10.1089/ham.2018.0112] [PMID: 31411500]
[41]
Alperin N, Hushek SG, Lee SH, Sivaramakrishnan A, Lichtor T. MRI study of cerebral blood flow and CSF flow dynamics in an upright posture: The effect of posture on the intracranial compliance and pressure. Acta Neurochir Suppl (Wien) 2005; 95: 177-81.
[http://dx.doi.org/10.1007/3-211-32318-X_38] [PMID: 16463846]
[42]
Wilson MH, Imray CHE. The cerebral venous system and hypoxia. J Appl Physiol 2016; 120(2): 244-50.
[http://dx.doi.org/10.1152/japplphysiol.00327.2015] [PMID: 26294747]
[43]
Wilson MH, Imray CH, Hargens AR. The headache of high altitude and microgravity--similarities with clinical syndromes of cerebral venous hypertension. High Alt Med Biol 2011; 12(4): 379-86.
[http://dx.doi.org/10.1089/ham.2011.1026] [PMID: 22087727]
[44]
Moses KL, Beshish AG, Heinowski N, et al. Effect of body position and oxygen tension on foramen ovale recruitment. Am J Physiol Regul Integr Comp Physiol 2015; 308(1): R28-33.
[http://dx.doi.org/10.1152/ajpregu.00263.2014] [PMID: 25394826]
[45]
Taibi A, Gadda G, Gambaccini M, Menegatti E, Sisini F, Zamboni P. Investigation of cerebral venous outflow in microgravity. Physiol Meas 2017; 38(11): 1939-52.
[http://dx.doi.org/10.1088/1361-6579/aa8980] [PMID: 28857747]
[46]
Mutlak O, Aslam M, Standfield N. The influence of exercise on ulcer healing in patients with chronic venous insufficiency. Int Angiol 2018; 37(2): 160-8.
[http://dx.doi.org/10.23736/S0392-9590.18.03950-0] [PMID: 29368880]
[47]
Stegall H. Muscle pumping in the independent leg. Circ Res 1966; 19(1): 180-90.
[http://dx.doi.org/10.1161/01.RES.19.1.180]
[48]
Bauer A, Demetz F, Bruegger D, et al. Effect of high altitude and exercise on microvascular parameters in acclimatized subjects. Clin Sci (Lond) 2006; 110(2): 207-15.
[http://dx.doi.org/10.1042/CS20050217] [PMID: 16194151]
[49]
Atar M, Söylemez H, Oguz F, et al. Effects of acute exercise on the diameter of the spermatic vein, and duration of reflux in patients with varicocele. Scand J Urol 2013; 47(3): 206-10.
[http://dx.doi.org/10.3109/00365599.2012.727467] [PMID: 23035729]
[50]
Braedel HU, Steffens J, Ziegler M, Polsky MS, Platt ML. A possible ontogenic etiology for idiopathic left varicocele. J Urol 1994; 151(1): 62-6.
[http://dx.doi.org/10.1016/S0022-5347(17)34872-3] [PMID: 8254834]
[51]
Cuypers J, Matakas F, Potolicchio SJ Jr. Effect of central venous pressure on brain tissue pressure and brain volume. J Neurosurg 1976; 45(1): 89-94.
[http://dx.doi.org/10.3171/jns.1976.45.1.0089] [PMID: 932805]
[52]
Mutlak O, Aslam M, Standfield NJ. Chronic venous insufficiency: A new concept to understand pathophysiology at the microvascular level - a pilot study. Perfusion 2019; 34(1): 84-9.
[http://dx.doi.org/10.1177/0267659118791682] [PMID: 30067139]
[53]
Gandhi J, Dagur G, Sheynkin YR, Smith NL, Khan SA. Testicular compartment syndrome: An overview of pathophysiology, etiology, evalu-ation, and management. Transl Androl Urol 2016; 5(6): 927-34.
[http://dx.doi.org/10.21037/tau.2016.11.05] [PMID: 28078225]

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