title: Interactive effects of maternal cigarette smoke, heat stress, hypoxia, and lipopolysaccharide on neonatal cardiorespiratory and cytokine responses.
abstract: Maternal cigarette smoke (CS) exposure exhibits a strong epidemiological association with Sudden Infant Death Syndrome, but other environmental stressors, including infection, hyperthermia, and hypoxia, have also been postulated as important risk factors. This study examines whether maternal CS exposure causes maladaptations within homeostatic control networks by influencing the response to lipopolysaccharide, heat stress, and/or hypoxia in neonatal rats. Pregnant dams were exposed to CS or parallel sham treatments daily for the length of gestation. Offspring were studied at postnatal days 6-8 at ambient temperatures (Ta) of 33°C or 38°C. Within each group, rats were allocated to control, saline, or LPS (200 µg/kg) treatments. Cardiorespiratory patterns were examined using head-out plethysmography and ECG surface electrodes during normoxia and hypoxia (10% O2). Serum cytokine concentrations were quantified from samples taken at the end of each experiment. Our results suggest maternal CS exposure does not alter minute ventilation (V̇e) or heart rate (HR) response to infection or high temperature, but independently increases apnea frequency. CS also primes the inflammatory system to elicit a stronger cytokine response to bacterial insult. High Taindependently depresses V̇e but augments the hypoxia-induced increase in V̇e Moreover, higher Taincreases HR during normoxia and hypoxia, and in the presence of an immune challenge, increases HR during normoxia, and reduces the increase normally associated with hypoxia. Thus, while most environmental risk factors increase the burden on the cardiorespiratory system in early life, hyperthermia and infection blunt the normal HR response to hypoxia, and gestational CS independently destabilizes breathing by increasing apneas.
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Faculty of Medicine, University of Calgary, Alberta, Canada; and.
authors.forename: Fiona B
authors.initials: FB
authors.lastname: McDonald
authors.affiliation: Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Faculty of Medicine, Health Sciences Centre, University of Calgary, Alberta, Canada.
authors.forename: Kumaran
authors.initials: K
authors.lastname: Chandrasekharan
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Faculty of Medicine, University of Calgary, Alberta, Canada; and.
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Wilson
authors.affiliation: Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Faculty of Medicine, Health Sciences Centre, University of Calgary, Alberta, Canada hasans@ucalgary.ca.
authors.forename: Shabih U
authors.initials: SU
authors.lastname: Hasan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000097:blood; D005260:Female; D006339:Heart Rate; D018869:Heat-Shock Response; D000860:Hypoxia / Q000503:physiopathology*; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D012123:Pulmonary Ventilation; D017207:Rats, Sprague-Dawley; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014028:Tobacco Smoke Pollution
keywords: apnea; hyperthermia; infant; inflammation; sudden infant death syndrome