{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T23:28:22Z","timestamp":1789342102998,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Caffeine is widely used to improve neonatal health in animals with low vitality. Due to its pharmacokinetics and pharmacodynamics, caffeine stimulates the cardiorespiratory system by antagonism of adenosine receptors and alteration in Ca+2 ion channel activity. Moreover, the availability of intracellular Ca+2 also has positive inotropic effects by increasing heart contractibility and by having a possible positive effect on neonate vitality. Nonetheless, since neonatal enzymatic and tissular systems are immature at birth, there is a controversy about whether caffeine is an effective therapy for newborns. This review aims to analyze the basic concepts of caffeine in neonatal animal models (rat and mouse pups, goat kids, lambs, and piglets), and it will discuss the neuroprotective effect and its physiological actions in reducing apnea in newborns.<\/jats:p>","DOI":"10.3390\/ani13111769","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:16:04Z","timestamp":1685204164000},"page":"1769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cardiorespiratory and Neuroprotective Effects of Caffeine in Neonate Animal Models"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-0367","authenticated-orcid":false,"given":"Daniel","family":"Mota-Rojas","sequence":"first","affiliation":[{"name":"Neurophysiology, Behavior and Animal Welfare Assessment, Universidad Aut\u00f3noma Metropolitana (UAM), Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3910-809X","authenticated-orcid":false,"given":"Dina","family":"Villanueva-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Division of Neonatology, National Institute of Health, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-2906","authenticated-orcid":false,"given":"Ismael","family":"Hern\u00e1ndez-\u00c1valos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Veterinary Anesthesia, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Cuautitl\u00e1n 54714, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8382-8388","authenticated-orcid":false,"given":"Alejandro","family":"Casas-Alvarado","sequence":"additional","affiliation":[{"name":"Neurophysiology, Behavior and Animal Welfare Assessment, Universidad Aut\u00f3noma Metropolitana (UAM), Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1584-0654","authenticated-orcid":false,"given":"Adriana","family":"Dom\u00ednguez-Oliva","sequence":"additional","affiliation":[{"name":"Neurophysiology, Behavior and Animal Welfare Assessment, Universidad Aut\u00f3noma Metropolitana (UAM), Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0084-8135","authenticated-orcid":false,"given":"Karina","family":"Lezama-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Neurophysiology, Behavior and Animal Welfare Assessment, Universidad Aut\u00f3noma Metropolitana (UAM), Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0052-861X","authenticated-orcid":false,"given":"Agatha","family":"Miranda-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Veterinary Anesthesia, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Cuautitl\u00e1n 54714, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-4261","authenticated-orcid":false,"given":"Julio","family":"Mart\u00ednez-Burnes","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia, Universidad Aut\u00f3noma de Tamaulipas, Victoria City 87000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"ref_1","first-page":"143","article-title":"VI. Nomenclature and classification of purinoceptors","volume":"46","author":"Fredholm","year":"1994","journal-title":"Pharmacol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101183","DOI":"10.1016\/j.siny.2020.101183","article-title":"Pharmacokinetics, pharmacodynamics and metabolism of caffeine in newborns","volume":"25","author":"Aranda","year":"2020","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_3","first-page":"30","article-title":"A primer on caffeine pharmacology and its drug interactions in clinical psychopharmacology","volume":"35","author":"Donovan","year":"2001","journal-title":"Psychopharmacol. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/cns.12684","article-title":"The neuroprotective effects of caffeine in neurodegenerative diseases","volume":"23","author":"Kolahdouzan","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1203\/00006450-200201000-00004","article-title":"Perinatal respiratory control and its modulation by adenosine and caffeine in the rat","volume":"51","author":"Herlenius","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.amjmed.2010.10.017","article-title":"Caffeine and cardiac arrhythmias: A review of the evidence","volume":"124","author":"Pelchovitz","year":"2011","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1055\/s-0033-1361933","article-title":"Medication use in the neonatal intensive care unit","volume":"31","author":"Hsieh","year":"2014","journal-title":"Am. J. Perinatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1056\/NEJMoa054065","article-title":"Caffeine therapy for apnea of prematurity","volume":"354","author":"Schmidt","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1600-0773.1995.tb00111.x","article-title":"Adenosine, adenosine receptors and the actions of caffeine","volume":"76","author":"Fredholm","year":"1995","journal-title":"Pharmacol. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.fct.2018.06.002","article-title":"Review of animal studies on the cardiovascular effects of caffeine","volume":"118","author":"Beyer","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF00613933","article-title":"The absolute bioavailability of caffeine in man","volume":"24","author":"Blanchard","year":"1983","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1542\/peds.2006-2986","article-title":"Therapeutic Drug Monitoring for Caffeine in Preterm Neonates: An Unnecessary Exercise?","volume":"119","author":"Natarajan","year":"2007","journal-title":"Pediatrics"},{"key":"ref_13","first-page":"207","article-title":"Pharmacokinetics of oral caffeine in sows: A pilot study","volume":"21","author":"Menozzi","year":"2015","journal-title":"Large Anim. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/S0009-9236(97)90097-7","article-title":"Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity","volume":"61","author":"Lee","year":"1997","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"446","DOI":"10.4062\/biomolther.2015.197","article-title":"Pharmacokinetic interaction of chrysin with caffeine in rats","volume":"24","author":"Noh","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3109\/00498258509049099","article-title":"Caffeine disposition after oral administration to pregnant rats","volume":"15","author":"Jiritano","year":"1985","journal-title":"Xenobiotica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/toxsci\/4.2part1.240","article-title":"Blood flow changes and conceptual development in pregnant rats in response to caffeine","volume":"4","author":"Kimmel","year":"1984","journal-title":"Toxicol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/FPC.0b013e32834aeedb","article-title":"PharmGKB summary","volume":"22","author":"Thorn","year":"2012","journal-title":"Pharmacogenet. Genom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"81","DOI":"10.5409\/wjcp.v4.i4.81","article-title":"Caffeine therapy in preterm infants","volume":"4","year":"2015","journal-title":"World J. Clin. Pediatr."},{"key":"ref_20","first-page":"178","article-title":"Caffeine metabolism in liver slices during postnatal development in rats","volume":"21","author":"Bienvenu","year":"1993","journal-title":"Drug Metab. Dispos."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1542\/peds.76.5.834","article-title":"Maturational changes of caffeine concentrations and disposition in infancy during maintenance therapy for apnea of prematurity: Influence of gestational age, hepatic disease, and breast-feeding","volume":"76","author":"Billon","year":"1985","journal-title":"Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"151","DOI":"10.15537\/smj.2021.2.25695","article-title":"Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats","volume":"42","author":"Alshabi","year":"2021","journal-title":"Saudi Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kumar, H.S.B., and Lipshultz, E.S. (2019). Caffeine and clinical outcomes in premature neonates. Children, 6.","DOI":"10.3390\/children6110118"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.neuropharm.2015.11.007","article-title":"Purinergic signaling in brain ischemia","volume":"104","author":"Pedata","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_25","first-page":"527","article-title":"International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors","volume":"53","author":"Fredholm","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/0165-3806(95)00120-3","article-title":"The ontogeny of cardiac and neural A1 adenosine receptor expression in rats","volume":"89","author":"Rivkees","year":"1995","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0304-3940(83)90222-7","article-title":"Differential location of adenosine A1 and A2 receptors in striatum","volume":"41","author":"Wojcik","year":"1983","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.neuro.2016.11.012","article-title":"Caffeine for apnea of prematurity: Effects on the developing brain","volume":"58","author":"Atik","year":"2017","journal-title":"Neurotoxicology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"225","DOI":"10.20882\/adicciones.303","article-title":"Cafe\u00edna: Un nutriente, un f\u00e1rmaco, o una droga de abuso","volume":"19","year":"2007","journal-title":"Adicciones"},{"key":"ref_30","first-page":"e15032","article-title":"The Neurophysiology of caffeine as a Central Nervous System stimulant and the resultant effects on cognitive function","volume":"13","author":"Fiani","year":"2021","journal-title":"Cureus"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000475895","article-title":"Caffeine and cannabis effects on vital neurotransmitters and enzymes in the brain tissue of juvenile experimental rats","volume":"24","author":"Owolabi","year":"2017","journal-title":"Ann. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fnins.2011.00116","article-title":"Energy drinks and the neurophysiological impact of caffeine","volume":"5","author":"Persad","year":"2011","journal-title":"Front. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1161\/01.RES.87.12.1095","article-title":"Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C","volume":"87","author":"Kamp","year":"2000","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.tins.2012.12.003","article-title":"Adenosine: Setting the stage for plasticity","volume":"36","author":"Dias","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1113\/jphysiol.1992.sp019125","article-title":"A caffeine- and ryanodine-sensitive Ca2+ store in bullfrog sympathetic neurons modulates effects of Ca2+ entry on [Ca2+]i","volume":"450","author":"Friel","year":"1992","journal-title":"J. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1113\/jphysiol.1985.sp015878","article-title":"The effects of caffeine and ryanodine on the electrical activity of the canine coronary sinus","volume":"368","author":"Aronson","year":"1985","journal-title":"J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1042\/BJ20080489","article-title":"Caffeine induces Ca2+ release by reducing the threshold for luminal Ca2+ activation of the ryanodine receptor","volume":"414","author":"Kong","year":"2008","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1139\/H08-121","article-title":"Effect of caffeine on the neuromuscular system\u2014Potential as an ergogenic aid","volume":"33","author":"Tarnopolsky","year":"2008","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000322696","article-title":"Caffeine and creatine use in sport","volume":"57","author":"Tarnopolsky","year":"2011","journal-title":"Ann. Nutr. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1038\/s41598-020-59196-9","article-title":"Ryanodine receptor modulation by caffeine challenge modifies Na+ current properties in intact murine skeletal muscle fibers","volume":"10","author":"Matthews","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jpeds.2021.08.075","article-title":"Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018","volume":"240","author":"Stark","year":"2022","journal-title":"J. Pediatr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.rmed.2016.01.022","article-title":"The potential of methylxanthine-based therapies in pediatric respiratory tract diseases","volume":"112","author":"Franco","year":"2016","journal-title":"Respir. Med."},{"key":"ref_43","first-page":"CD000273","article-title":"Caffeine versus theophylline for apnea in preterm infants","volume":"20","author":"Steer","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_44","first-page":"43","article-title":"Caffeine as an analgesic adjuvant: A review of pharmacology and mechanisms of action","volume":"45","author":"Sawynok","year":"1993","journal-title":"Pharmacol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1651-2227.2005.tb01794.x","article-title":"Lung function in immature baboons with respiratory distress syndrome receiving early caffeine therapy: A pilot study","volume":"94","author":"Yoder","year":"2007","journal-title":"Acta Paediatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/pr.2012.49","article-title":"Effects of caffeine on renal and pulmonary function in preterm newborn lambs","volume":"72","author":"Crossley","year":"2012","journal-title":"Pediatr. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0034-5687(80)90094-8","article-title":"Caffeine effect on breathing pattern and vagal reflexes in newborn rabbits","volume":"40","author":"Trippenbach","year":"1980","journal-title":"Respir. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1203\/PDR.0b013e3181e5bc78","article-title":"Caffeine reduces apnea frequency and enhances ventilatory long-term facilitation in rat pups raised in chronic intermittent hypoxia","volume":"68","author":"Julien","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1203\/01.pdr.0000203105.63246.8a","article-title":"Long-term consequences of neonatal caffeine on ventilation, occurrence of apneas, and hypercapnic chemoreflex in male and female rats","volume":"59","author":"Montandon","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"R1621","DOI":"10.1152\/ajpregu.00514.2006","article-title":"Disruption of adenosinergic modulation of ventilation at rest and during hypercapnia by neonatal caffeine in young rats: Role of adenosine A1 and A2A receptors","volume":"292","author":"Montandon","year":"2007","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R922","DOI":"10.1152\/ajpregu.00059.2008","article-title":"Neonatal caffeine induces sex-specific developmental plasticity of the hypoxic respiratory chemoreflex in adult rats","volume":"295","author":"Montandon","year":"2008","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Henderson-Smart, D.J., and Davis, P.G. (2010). Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst. Rev., CD000139.","DOI":"10.1002\/14651858.CD000139.pub2"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1177\/000992280003900602","article-title":"Current options in the management of apnea of prematurity","volume":"39","author":"Bhatia","year":"2000","journal-title":"Clin. Pediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1159\/000360647","article-title":"Caffeine for apnea of prematurity: A neonatal success story","volume":"105","author":"Kreutzer","year":"2014","journal-title":"Neonatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1440-1754.2009.01570.x","article-title":"Caffeine versus theophylline for apnea of prematurity: A randomised controlled trial","volume":"45","author":"Skouroliakou","year":"2009","journal-title":"J. Paediatr. Child Health"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Miao, Y., Zhou, Y., Zhao, S., Liu, W., Wang, A., Zhang, Y., Li, Y., and Jiang, H. (2022). Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity: A systematic review and meta-analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274882"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"L586","DOI":"10.1152\/ajplung.00405.2016","article-title":"Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury","volume":"312","author":"Teng","year":"2017","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1001\/jama.2018.21443","article-title":"Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation","volume":"321","author":"Onland","year":"2019","journal-title":"JAMA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"902437","DOI":"10.3389\/fped.2022.902437","article-title":"Molecular Mechanism of Caffeine in Preventing Bronchopulmonary Dysplasia in Premature Infants","volume":"10","author":"Tian","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3389\/fmed.2015.00090","article-title":"Understanding the Impact of Infection, Inflammation, and Their Persistence in the Pathogenesis of Bronchopulmonary Dysplasia","volume":"2","author":"Balany","year":"2015","journal-title":"Front. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1183\/09031936.00012412","article-title":"Prevention of hyperoxia-mediated pulmonary inflammation in neonatal rats by caffeine","volume":"41","author":"Weichelt","year":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/pr.2013.233","article-title":"Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse lung","volume":"75","author":"Dayanim","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1203\/PDR.0b013e3180a725b1","article-title":"The Effects of Caffeine on the Preterm Sheep Ductus Arteriosus","volume":"62","author":"Clyman","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_64","first-page":"83","article-title":"Actions of caffeine in the brain with special reference to factors that contribute to its widespread use","volume":"51","author":"Fredholm","year":"1999","journal-title":"Pharmacol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jacep.2018.01.012","article-title":"Caffeine and arrhythmias: Time to grind the data","volume":"4","author":"Voskoboinik","year":"2018","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1113\/expphysiol.2005.031559","article-title":"Caffeine administration results in greater tension development in previously fatigued canine muscle in situ","volume":"90","author":"Howlett","year":"2005","journal-title":"Exp. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1161\/01.RES.60.4.495","article-title":"Effects of ryanodine and caffeine on contractility, membrane voltage, and calcium exchange in cultured heart cells","volume":"60","author":"Rasmussen","year":"1987","journal-title":"Circ. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1203\/00006450-199709000-00007","article-title":"Caffeine-induced contractions in developing rabbit heart","volume":"42","author":"Miller","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1023\/A:1005496708505","article-title":"Caffeine and excitation\u2013contraction coupling in skeletal muscle: A stimulating story","volume":"20","year":"1999","journal-title":"J. Muscle Res. Cell. Motil."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1538\/expanim.20-0185","article-title":"Caffeine: Cardiorespiratory effects and tissue protection in animal models","volume":"70","year":"2021","journal-title":"Exp. Anim."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1017\/S1751731117001446","article-title":"Caffeine supplementation of ewes during lambing may increase lamb survival","volume":"12","author":"Robertson","year":"2018","journal-title":"Animal"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1253\/jcj.60.157","article-title":"Caffeine Induces Ventricular Tachyarrhythmias Possibly Due to Triggered Activity in Rabbits in Vivo","volume":"60","author":"Ishida","year":"1996","journal-title":"Jpn. Circ. J."},{"key":"ref_73","first-page":"273","article-title":"Caffeine and cardiac arrhythmias. An experimental study in dogs with review of literature","volume":"52","author":"Mehta","year":"1997","journal-title":"Acta Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1046\/j.1523-1755.2002.00278.x","article-title":"Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa-facp) rats","volume":"61","author":"Tofovic","year":"2002","journal-title":"Kidney Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ptr.3333","article-title":"The Effect of Four Coffee types on Normotensive rats and Normal\/Hypertensive Human Volunteers","volume":"25","author":"Awaad","year":"2011","journal-title":"Phyther. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.jelectrocard.2005.12.007","article-title":"The effects of caffeine on the inducibility of atrial fibrillation","volume":"39","author":"Rashid","year":"2006","journal-title":"J. Electrocardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.2460\/ajvr.69.12.1670","article-title":"Effects of intravenous administration of caffeine on physiologic variables in exercising horses","volume":"69","author":"Ferraz","year":"2008","journal-title":"Am. J. Vet. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2460\/ajvr.1995.56.05.619","article-title":"Pharmacokinetics of caffeine in lactating dairy cows","volume":"56","author":"DeGraves","year":"1995","journal-title":"Am. J. Vet. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/s41390-019-0718-8","article-title":"Long-term neurological effects of neonatal caffeine treatment in a rabbit model of preterm birth","volume":"87","author":"Gerdtsson","year":"2020","journal-title":"Pediatr. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3840124","DOI":"10.1155\/2020\/3840124","article-title":"Prevention of Oxygen-Induced Inflammatory Lung Injury by Caffeine in Neonatal Rats","volume":"2020","author":"Endesfelder","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Winerdal, M.M.E., Urmaliya, V., Winerdal, M.M.E., Fredholm, B.B., Winqvist, O., and \u00c5d\u00e9n, U. (2017). Single dose caffeine protects the neonatal mouse brain against hypoxia ischemia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170545"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"298","DOI":"10.31893\/jabb.20039","article-title":"Neurobehavioral and neuroprotector effects of caffeine in animal models","volume":"8","year":"2020","journal-title":"J. Anim. Behav. Biometeorol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e540","DOI":"10.1542\/neo.14-11-e540","article-title":"Pharmacology review. Caffeine use in neonates: Indications, pharmacokinetics, clinical effects, outcomes","volume":"14","author":"Dobson","year":"2013","journal-title":"Neoreviews"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"908045","DOI":"10.3389\/fcell.2022.908045","article-title":"Caffeine Restores Neuronal Damage and Inflammatory Response in a Model of Intraventricular Hemorrhage of the Preterm Newborn","volume":"10","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"724161","DOI":"10.3389\/fped.2021.724161","article-title":"Encephalopathy in preterm infants: Advances in neuroprotection with caffeine","volume":"9","author":"Yang","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1056\/NEJMoa073679","article-title":"Long-term effects of caffeine therapy for apnea of prematurity","volume":"357","author":"Schmidt","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"147990","DOI":"10.1016\/j.brainres.2022.147990","article-title":"The effects of caffeine following hypoxic-ischemic encephalopathy: A systematic review of animal studies","volume":"1790","author":"Bruschettini","year":"2022","journal-title":"Brain Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/cns.13834","article-title":"Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic-ischemic white matter damage","volume":"28","author":"Yang","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1038\/s41390-021-01924-6","article-title":"Caffeine treatment started before injury reduces hypoxic\u2013ischemic white-matter damage in neonatal rats by regulating phenotypic microglia polarization","volume":"92","author":"Yang","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000509365","article-title":"Caffeine restores background EEG activity independent of infarct reduction after neonatal hypoxic ischemic brain injury","volume":"42","author":"Sun","year":"2020","journal-title":"Dev. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1017\/S175173111900301X","article-title":"Caffeine supplementation at birth, but not 8 to 12 h post-birth, increased 24 h pre-weaning mortality in piglets","volume":"14","author":"Nowland","year":"2020","journal-title":"Animal"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Jarratt, L., James, S.E., Kirkwood, R.N., and Nowland, T.L. (2023). Effects of caffeine and glucose supplementation at birth on piglet pre-weaning growth, thermoregulation, and survival. Animals, 13.","DOI":"10.3390\/ani13030435"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"106715","DOI":"10.1016\/j.anireprosci.2021.106715","article-title":"Supplementing pregnant Merino ewes with caffeine to improve neonatal lamb thermoregulation and viability","volume":"226","author":"Murdock","year":"2021","journal-title":"Anim. Reprod. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.anireprosci.2018.09.015","article-title":"Oral caffeine administered during late gestation increases gestation length and piglet temperature in naturally farrowing sows","volume":"198","author":"Dearlove","year":"2018","journal-title":"Anim. Reprod. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"106799","DOI":"10.1016\/j.anireprosci.2021.106799","article-title":"Maternal caffeine administration to ewes does not affect perinatal lamb survival","volume":"231","author":"Robertson","year":"2021","journal-title":"Anim. Reprod. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"108479","DOI":"10.1016\/j.neuropharm.2021.108479","article-title":"Caffeine exposure in utero is associated with structural brain alterations and deleterious neurocognitive outcomes in 9\u201310 year old children","volume":"186","author":"Christensen","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"McLeod, R., Rosenkrantz, T., and Fitch, R.H. (2022). Therapeutic Interventions in Rat Models of Preterm Hypoxic Ischemic Injury: Effects of Hypothermia, Caffeine, and the Influence of Sex. Life, 12.","DOI":"10.3390\/life12101514"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"724145","DOI":"10.3389\/fphar.2021.724145","article-title":"Caffeine Therapy for Apnea of Prematurity: Role of the Circadian CLOCK Gene Polymorphism","volume":"12","author":"Guo","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1053210","DOI":"10.3389\/fphar.2022.1053210","article-title":"Precision caffeine therapy for apnea of prematurity and circadian rhythms: New possibilities open up","volume":"13","author":"Dai","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.rvsc.2006.11.010","article-title":"Annual rhythmicity and maturation of physiological parameters in goats","volume":"83","author":"Piccione","year":"2007","journal-title":"Res. Vet. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4067\/S0716-97602008000100007","article-title":"Chronobiologic blood pressure assessment: Maturation of the daily rhythm in newborn foals","volume":"41","author":"Piccione","year":"2008","journal-title":"Biol. Res."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/11\/1769\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:42:40Z","timestamp":1760125360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/11\/1769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,26]]},"references-count":101,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ani13111769"],"URL":"https:\/\/doi.org\/10.3390\/ani13111769","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,26]]}}}