During phototherapy of jaundiced newborns, vasodilation occurs in the skin circulation compensated by vasoconstriction in the renal and mesenteric circulation. Furthermore, there is a slight decrease in cardiac systolic volume, and blood pressure, as well as an increase in heart rate and discrete changes in the heart rate variability (HRV). The primary change during phototherapy is the skin vasodilation mediated by multiple mechanisms: 1) Passive vasodilation induced by direct skin heating effect of the body surface and subcutaneous blood vessels, modified by myogenic autoregulation. 2) Active vasodilation mediated via the mechanism provided by axon reflexes through nerve C-fibers and humoral mechanism via nitric oxide (NO) and endothelin 1 (ET-1). During and after phototherapy is a rise in the NO:ET-1 ratio. 3) Regulation of the skin circulation through the sympathetic nerves is unique, but their role in skin vasodilation during phototherapy was not studied. 4) Special mechanism is a photorelaxation independent of the skin heating. Melanopsin (opsin 4) - is thought to play a major role in systemic vascular photorelaxation. Signalling cascade of the photorelaxation is specific, independent of endothelium and NO. The increased skin blood flow during phototherapy is enabled by the restriction of blood flow in the renal and mesenteric circulation. An increase in heart rate indicates activation of the sympathetic system as is seen in the measures of the HRV. High-pressure, as well as low-pressure baroreflexes, may play important role in these adaptation responses. The integrated complex and specific mechanism responsible for the hemodynamic changes during phototherapy confirm adequate and functioning regulation of the neonatal cardiovascular system, including baroreflexes.

Department of Physiology Jessenius Faculty of Medicine Comenius University Martin Slovak Republic

See more in PubMed

Hansen TWR. Phototherapy for neonatal jaundice--therapeutic effects on more than one level? Semin Perinatol. 2010;34:231–34. doi: 10.1053/j.semperi.2010.02.008. PubMed DOI

Dvořák A, Pospíšilová K, Žížalová K, Capková N, Muchová L, Vecka M, Vrzáčková N, Křížová J, Zelenka J, Vítek L. The effects of bilirubin and lumirubin on metabolic and oxidative stress markers. Front Pharmacol. 2021;12:567001. doi: 10.3389/fphar.2021.567001. PubMed DOI PMC

Bhutani VK. Committee on Fetus and Newborn; American Academy of Pediatrics. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2011;128:e1046–e1052. doi: 10.1542/peds.2011-1494. PubMed DOI

Wu PYK, Wong WH, Hodgman JE, Levan N. Changes in blood flow in the skin and muscle with phototherapy. Pediatr Res. 1974;8:257–62. doi: 10.1203/00006450-197404000-00007. PubMed DOI

Walther FJ, Wu PY, Siassi B. Cardiac output changes in newborns with hyperbilirubinemia treated with phototherapy. Pediatrics. 1985;76:918–921. doi: 10.1542/peds.76.6.918. PubMed DOI

Jahnukainen T, Lindqvist A, Jalonen J, Kero P, Valimaki I. Responsiveness of cutaneous vasculature to thermal stimulation during phototherapy in neonatal jaundice. Eur J Pediatr. 1999;158:757–760. doi: 10.1007/s004310051195. PubMed DOI

Yao AC, Martinussen M, Johansen OJ, Brubakk AM. Phototherapy associated changes in mesenteric blood flow response to feeding in term neonates. J Pediatr. 1994;124:309–312. doi: 10.1016/S0022-3476(94)70325-6. PubMed DOI

Pezzati M, Biagiotti R, Vangi V, Lombardi E, Wiechmann L, Rubaltelli FF. Changes in mesenteric blood flow response to feeding: conventional versus fibre-optic phototherapy. Pediatrics. 2000;105:350–353. doi: 10.1542/peds.105.2.350. PubMed DOI

Benders MJ, Van Bel F, van de Bor M. The effect of phototherapy on renal blood flow velocity in preterm infants. Biol Neonate. 1998;73:228–34. doi: 10.1159/000013981. PubMed DOI

Amato M, Donati F. Cerebral blood flow velocity in term infants treated with phototherapy. Brain Dev. 1991;13:417–419. doi: 10.1016/S0387-7604(12)80039-8. PubMed DOI

Benders MJ. The effect of phototherapy on cerebral blood flow velocity in preterm infants. Acta Paediatr. 1998;87:786–792. doi: 10.1111/j.1651-2227.1998.tb01748.x. PubMed DOI

Borenstein-Levin L, Sharif D, Amshalom A, Riskin A, Hemo M, Khalil A, Bader D, Kugelman A. Effects of Phototherapy on Coronary Blood Flow in Healthy Neonates: A Pilot Study. Neonatology. 2016;110:75–82. doi: 10.1159/000444244. PubMed DOI

Benders MJ, Van Bel F, van de Bor M. Cardiac output and ductal reopening during phototherapy in preterm infants. Acta Paediatr. 1999;88:1014–1019. doi: 10.1111/j.1651-2227.1999.tb00199.x. PubMed DOI

Firouzi M, Sherkatolabbasieh H, Nezami A, Shafizadeh S. Effect of phototherapy on stroke volume in newborn infants with jaundice. J Pediatr Intensive Care. 2020;9:207–09. doi: 10.1055/s-0040-1708556. PubMed DOI PMC

Javorka K, Zavarská L’. Zmeny systémového tlaku krvi a kardiorespiračných parametrov u nedonosených novorodencov počas fototerapie. (Article in Slovak) Cesk Pediatr. 1990;45:230–232. PubMed

Nandrážiová L, Javorka K, Czippelová B, Mat’ašová K. Zmeny tlaku krvi a niektorých d’alších parametrov počas fototerapie donosených novorodencov. (Article in Slovak) Česko-Slovenská Pediat. 2019;74:449–457.

Weissman A, Berkowitz E, Smolkin T, Blazer S. Effect of phototherapy on neonatal heart rate variability and complexity. Neonatology. 2009;95:41–46. doi: 10.1159/000151754. PubMed DOI

Uhríková Z, Zibolen M, Javorka K, Chládeková L, Javorka M. Hyperbilirubinemia phototherapy in newborns: Effect on cardiac autonomic control. Early Hum Dev. 2015;91:351–356. doi: 10.1016/j.earlhumdev.2015.03.009. PubMed DOI

Aydemir O, Soysaldı E, Kale Y, Kavurt S, Bas AY, Demirel N. Body temperature changes of newborns under fluorescent versus LED phototherapy. Ind J Pediatr. 2014;81:751–4. doi: 10.1007/s12098-013-1209-2. PubMed DOI

Pergola PE, Kellog DL, JR, Johnson JM, Kosiba WA, Solomon DE. Role of sympathetic nerves in the vascular effects of local temperature in human forearm skin. Am J Physiol. 1993;265:H785–H792. doi: 10.1152/ajpheart.1993.265.3.H785. PubMed DOI

Minson CT, Berry LT, Joyner MI. Nitric oxide and neurally mediated regulation of skin blood flow during local heating. J Appl Physiol. 2001;91:1619–1626. doi: 10.1152/jappl.2001.91.4.1619. PubMed DOI

Charkoudian N. Skin blood flow in adult human thermoregulation:how it works, when it does not, and why. Mayo Clin Proc. 2003;78:603–612. doi: 10.4065/78.5.603. PubMed DOI

Cracowski J-L, Roustit M. Human skin microcirculation. Compr Physiol. 2020;10:1105–1154. doi: 10.1002/cphy.c190008. PubMed DOI

Holzer P. Neurogenic vasodilatation and plasma leakage in the skin. Gen Pharmacol. 1998;30:5–11. doi: 10.1016/S0306-3623(97)00078-5. PubMed DOI

Shastry S, Minson CT, Wilson SA, Dietz NM, Joyner MJ. Effects of atropine and L-NAME on cutaneous blood flow during body heating in humans. J Appl Physiol. 2000;88:467–472. doi: 10.1152/jappl.2000.88.2.467. PubMed DOI

Schneider MP, Boesen EI, Pollock DM. Contrasting actions of endothelin ETA and ETB receptors in cardiovascular disease. Ann Rev Pharmacol Toxicol. 2007;47:731–759. doi: 10.1146/annurev.pharmtox.47.120505.105134. PubMed DOI PMC

Liu G-S, Wu H, WB-Q, Huang R-Z, Zhao L-H, Wen Y. Effect of phototherapy on blood endothelin and nitric oxide levels: clinical significance in preterm infants. World J Pediatr. 2008;4:31–35. doi: 10.1007/s12519-008-0006-x. PubMed DOI

Reber KM, Su BY, Clark KR, Clark KR, Pohlman DL, Miller CE, Nowicki PT. Developmental expression of eNOS in postnatal swine mesenteric artery. Am J Physiol. 2002;283:G1328–G1335. doi: 10.1152/ajpgi.00067.2002. PubMed DOI

Nankervis CA, Giannone PJ, Reber KM. The neonatal intestinal vasculature: Contributing factors to necrotizing enterocolitis. Semin Perinatol. 2008;32:83–91. doi: 10.1053/j.semperi.2008.01.003. PubMed DOI

Ergenekon E, Gücüyener K, Dursun H, Erbaş D, Oztürk G, Koç E, Atalay Y. Nitric oxide production in newborns under phototherapy. Nitric Oxide. 2002;6:69–72. doi: 10.1006/niox.2001.0364. PubMed DOI

Abu Faddan NH, Abd El-Aziz NHR, Abd El-Azeem HG, Shreif T. Effect of phototherapy on blood levels of endothelin-1 and nitric oxide in hyberbilirubinemic newborn infants. e-J Neonat Res. 2014;4:14–20.

Surmeli-Onay O, Yurdakok M, Karagoz T, Erkekoglu P, Ertugrul I, Takci S, Giray BK, Aykan HH, Korkmaz A, Yigit S. A new approach to an old hypothesis; phototherapy does not affect ductal patency via PGE2 and PGI2. J Matern Fetal Neonatal Med. 2015;28:16–2. doi: 10.3109/14767058.2014.899575. PubMed DOI

Yurdakök M. Phototherapy in the newborn: what's new? J Pediatr Neonat Individual Med. 2015;4:e040255. doi: 10.7363/040255. DOI

Wright IM, Dyson RM. Microcirculation of the Newborn. In: LENASI H, editor. Microcirculation Revisited. From Molecules to Clinical Practice. London: IntechOpen; 2016. pp. 81–100. https://www.intechopen.com/chapters/51870, https://doi.org/10.5772/64584. DOI

Johnson JM, Proppe DW. Cardiovascular adjustment to heat stress. In: FREGLZ MI, BLATTEIS CM, editors. Handbook of Physiology. I. Oxford University Press; New York: 1996. pp. 215–243. Section 4: Environmental Physiology. DOI

Kellog DL, JR, Liu Y, McAllister K, Friel C, Pergola PE. Bradykinin does not mediate cutaneous active vasodilation during heat stress in humans. J Appl Physiol. 2002;93:1215–1221. doi: 10.1152/japplphysiol.01142.2001. PubMed DOI

Kellog DL, Jr, Zhao JL, Wu Y, Johnson JM. VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans. J Appl Physiol. 2010;109:95–100. doi: 10.1152/japplphysiol.01187.2009. PubMed DOI PMC

Furchgott RF, Sleator WJ, McCaman MW, Elchlepp J. Relaxation of arterial strips by light and the influence of drugs on this photodynamic effect. J Pharmacol Exp Ther. 1955;113:122.

Sikka G, Hussmann GP, Pandey D, Cao S, Hori D, Park JT, Steppan J, et al. Melanopsin mediates light-dependent relaxation in blood vessels. Proc Natl Acad Sci U S A. 2014;111:17977–17982. doi: 10.1073/pnas.1420258111. PubMed DOI PMC

Batenburg WW, Kappers MHW, Eikmann MJ, Ramzan SNA, de Vries R, Danser AHJ. Light-induced vs. bradykinin-induced relaxation of coronary arteries: do S-nitrosothiols act as endothelium-derived hyperpolarizing factors? J Hypertens. 2009;27:1631–1640. doi: 10.1097/HJH.0b013e32832bff54. PubMed DOI

Yim PD, Gallos G, Perez-Zoghbi JF, Zhang Y, Xu D, Wu A, Berkowitz DE, Emala CW. Airway smooth muscle photorelaxation via opsin receptor activation. Am J Physiol Lung Cell Mol Physiol. 2019;316:L82–L93. doi: 10.1152/ajplung.00135.2018. PubMed DOI PMC

Stachurska A, Tadeusz Sarna T. Regulation of melanopsin signalling: key interactions of the nonvisual photopigment. Photochem Photobiol. 2019;95:83–94. doi: 10.1111/php.12995. PubMed DOI

Wahl S, Engelhardt M, Schaupp P, Lappe Ch, Ivanov I. The inner clock - blue light sets the human rhythm. J Biophotonics. 2019;12:e201900102. doi: 10.1002/jbio.201900102. PubMed DOI PMC

Barreto Ortiz S, Hori D, Nomura Y, Yun X, Jiang H, Yong H, Chen J, et al. Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G-protein-coupled receptor kinase 2 inhibition. Am J Physiol Lung Cell Mol Physiol. 2018;314:L93–L106. doi: 10.1152/ajplung.00091.2017. PubMed DOI PMC

Wu AD, Dan W, Zhang Yi, Vemaraju S, Upton BA, Lang BA, Buhr ED, Berkowitz DE, Gallos G, Emala CW, Yim PD. Opsin 3-Gαs promotes airway smooth muscle relaxation modulated by G protein receptor kinase 2. Am J Resp Cell Mol Biol. 2021;64:59–68. doi: 10.1165/rcmb.2020-0392OC. PubMed DOI PMC

Qiu X, Kumbalasin T, Carlson SM, Wong V, Krishna I, Provencio, Berson DM. Induction of photosensitivity by heterologous expression of melanopsin. Nature. 2005;433:745–749. doi: 10.1038/nature03345. PubMed DOI

Rao S, Chun C, Fan J, Kofron JM, Yang MB, Hegde RS, Ferrara N, Copenhagen DR, Lang RA. A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature. 2013;494:243–46. doi: 10.1038/nature11823. PubMed DOI PMC

Gournay V, Drouin E, Rozé JC. Development of baroreflex control of heart rate in preterm and full term infants. Arch Dis Child Fetal Neonatal Ed. 2002;86:F151–F154. doi: 10.1136/fn.86.3.F151. PubMed DOI PMC

Yiallourou SR, Sands SA, Walker AM, Horne RSC. Postnatal development of baroreflex sensitivity in infancy. J Physiol. 2010;588:2193–203. doi: 10.1113/jphysiol.2010.187070. PubMed DOI PMC

Haskova K, Javorka M, Czippelova B, Zibolen M, Javorka K. Baroreflex sensitivity in premature infants - relation to the parameters characterizing intrauterine and postnatal condition. Physiol Res. 2017;66(Suppl 2):S257–S264. doi: 10.33549/physiolres.933681. PubMed DOI

Javorka K, Haskova K, Czippelova B, Zibolen M, Javorka M. Baroreflex sensitivity and blood pressure in premature infants - Dependence on gestational age, postnatal age and sex. Physiol Res. 2021;70(Suppl 3):S349–S356. doi: 10.33549/physiolres.934829. PubMed DOI PMC

Chowdhary S, Vaile JC, Fletcher J, Ross HF, Coote JH, Townend JN. Nitric oxide and cardiac autonomic control in humans. Hypertension. 2000;36:264–69. doi: 10.1161/01.HYP.36.2.264. PubMed DOI

El-Masry HMA, Hassan AA, Hashim AM, Aladawy MAA, Abdelwahab AAA. Evaluation of serum endothelin-1 (ET-1) and nitric oxide (NO) levels in unconjugated hyperbilirubinemic neonates. Egypt J Hospit Med. 2020;81:1858–1865. doi: 10.21608/ejhm.2020.121012. DOI

Musialek P, Lei M, Brown HF, Paterson DJ, Casadei B. Nitric oxide can increase heart rate by stimulating the hyperpolarization-activated inward current, I(f) Circ Res. 1997;81:60–68. doi: 10.1161/01.RES.81.1.60. PubMed DOI