{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T23:03:53Z","timestamp":1743807833543},"reference-count":68,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2012,10,19]],"date-time":"2012-10-19T00:00:00Z","timestamp":1350604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>A rise in heart rate boosts cardiac output and blood pressure, improves perfusion and oxygen delivery, and speeds recovery during an emergency.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Breathing efforts and lung inflation reflexively elevate heart rate during experimental asphyxia, and may rescue (\u2018auto resuscitate\u2019) an animal from imminent death.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We analysed whether this mechanism elevates heart rate when a healthy, sleeping infant is confronted by mild, progressive asphyxia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Term\u2010born infants aged 1\u20138 days rebreathed the expired gas for short periods to stimulate breathing and heart rate but not arousal from sleep.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that a rising CO<jats:sub>2<\/jats:sub> level during asphyxia is much more strongly cardio\u2010acceleratory than either vigorous breathing efforts or lung inflation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This excitatory action of CO<jats:sub>2<\/jats:sub> on the heart develops soon after birth.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We suggest that (i) the hypercapnia during asphyxia helps raise heart rate; (ii) excitation by respiratory manoeuvres alone is relatively weak and short lived and may not produce the sustained heart rate rise needed to counteract circulatory depression.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold> A resumption of, and escalation in, breathing efforts (hyperpnoea) reflexively accelerates heart rate (HR) and may facilitate cardiac and circulatory recovery from apnoea. We analysed whether this mechanism can produce a sustained rise in HR (tachycardia) when a sleeping infant is confronted by mild, rapidly worsening asphyxia, simulating apnoea. Twenty\u2010seven healthy term\u2010born infants aged 1\u20138 days rebreathed the expired gas for 90 s during quiet sleep to stimulate breathing and heart rate. To discriminate cardio\u2010excitatory effects of central respiratory drive, lung inflation, hypoxia, hypercapnia and asphyxia, we varied the inspired O<jats:sub>2<\/jats:sub> level and compared temporal changes in response profiles as respiratory sensitivity to hypoxia and asphyxia \u2018reset\u2019 after birth. We demonstrate that asphyxia\u2010induced hyperpnoea and tachycardia strengthen dramatically over the first week with different time courses and via separate mechanisms. Cardiac excitation by hypercapnia improves first, followed by a slower improvement in respiratory hypoxic drive. A rise in CO<jats:sub>2<\/jats:sub> consequently elicits stronger, longer lasting tachycardia than moderate increases in respiratory drive or lung expansion. We suggest that without a strong facilitating action of CO<jats:sub>2<\/jats:sub> on the immature heart, respiratory manoeuvres may be unable to reflexively counteract strong vagal bradycardia. This may increase the vulnerability of some infants to apnoea \u2013 asphyxia.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.239145","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T01:32:08Z","timestamp":1348536728000},"page":"6157-6165","source":"Crossref","is-referenced-by-count":9,"title":["A key circulatory defence against asphyxia in infancy \u2013 the heart of the matter!"],"prefix":"10.1113","volume":"590","author":[{"given":"Gary","family":"Cohen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Katz\u2010Salamon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girvan","family":"Malcolm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,10,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1978.sp012152"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1964.19.3.479"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.3.H1145"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1542\/peds.45.2.206","article-title":"Chemoreceptor reflexes in the newborn infant: effect of CO2 on the ventilatory response to hypoxia","volume":"45","author":"Brady JP","year":"1970","journal-title":"Pediatrics"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.3.837"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2001.tb02807.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15323-8"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2005.04.009"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80841-8"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01152.2011"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020137"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1203\/pdr.0b013e318030d0ef"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.203bi.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.783902"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.229641"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.71.1.168"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)91218-2"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1963.sp007051"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104454"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.87.1.203"},{"key":"e_1_2_6_22_1","first-page":"242","article-title":"Influences of hypercapnia on cardiac function in the newborn lamb","volume":"43","author":"Downing SE","year":"1971","journal-title":"Yale J Biol Med"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.10.4.676"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb02827.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0838.2005.00440.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.1038"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.83.5.423"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(68)90037-6"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1152\/jappl.1994.76.5.1968","article-title":"Maturational differences in step vs. ramp hypoxic and hypercapnic ventilatory responses","volume":"76","author":"Gozal D","year":"1994","journal-title":"J Appl Physiol"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199205000-00016"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.3.763"},{"key":"e_1_2_6_32_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/sleep\/3.3-4.331","article-title":"Vulnerability to hypoxemia in the newborn","volume":"3","author":"Henderson\u2010Smart DJ","year":"1980","journal-title":"Sleep"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1988.tb37256.x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.62.12.1238"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02240461"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20745"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00551-0"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.79.3.231"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(81)90074-6"},{"key":"e_1_2_6_40_1","first-page":"161","volume-title":"Fetal and Neonatal Physiology","author":"Lagercrantz H","year":"1992"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1980.48.3.468"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1958.sp001319"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(82)80009-7"},{"key":"e_1_2_6_44_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1542\/peds.93.1.44","article-title":"Cardiorespiratory recordings from infants dying suddenly and unexpectedly at home","volume":"93","author":"Meny RG","year":"1994","journal-title":"Pediatrics"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(97)00024-8"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(99)00003-1"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.79.1.205"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(85)90093-3"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/146.1.11"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/146.5_Pt_1.1206"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1095-6433(98)01009-5"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020749"},{"key":"e_1_2_6_53_1","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1152\/jappl.1993.75.5.2209","article-title":"Ventilatory sensitivity to CO2 in hyperoxia and hypoxia in older aged humans","volume":"75","author":"Poulin MJ","year":"1993","journal-title":"J Appl Physiol"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(74)90454-5"},{"key":"e_1_2_6_55_1","first-page":"745","volume-title":"Regulation of Breathing","author":"Rebuck AS","year":"1981"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1975.39.6.896"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/32567"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1960.15.3.454"},{"key":"e_1_2_6_59_1","first-page":"710","volume-title":"Fetal and Neonatal Physiology","author":"Serwer G","year":"1992"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1139\/y02-148"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(00)00122-5"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200104000-00019"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp019997"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.10287"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1139\/y96-049"},{"key":"e_1_2_6_66_1","first-page":"759","volume-title":"Fetal and Neonatal Physiology","author":"Talner N","year":"1992"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19971117)388:2<169::AID-CNE1>3.0.CO;2-#"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1988.tb37261.x"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.65.1.309"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2012.239145","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2012.239145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T12:05:39Z","timestamp":1697285139000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2012.239145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,19]]},"references-count":68,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1113\/jphysiol.2012.239145"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2012.239145","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,19]]}}}