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Postnatal Lung Function Following Prenatal Nicotine Exposure
Dr. Sundell has previously performed studies on young lambs to determine whether lung function in the developing lamb is altered by prenatal exposure to a low or moderate dose of nicotine during the last trimester (0.5 and 1.5 mg/kg/d, respectively). The nicotine plasma concentrations achieved with these doses correspond to those observed in human smokers smoking < 10 and approximately 20 cigarettes per day. Lung mechanics, lung volume and airway reactivity to methacholine or acute hypoxia were determined at 12, 25 and 51d. The studies were performed in collaboration with Dr. Kenneth Sandberg at the University of Gothenburg, Sweden, and Dr. Kent Pinkerton, UC at Davis. Results of baseline measurements describing a significantly reduced specific airway conductance and improved distal airway function in the nicotine-exposed lambs were published in Pediatric Research in 2004.

The response to acute hypoxia (0.1 FiO2) was also studied in these lambs. Results showed an absent increase in Cdyn and lung volume together with increased airway reactivity in response to hypoxic stress in lambs exposed to a moderate dose of nicotine prenatally compared with control lambs or lambs exposed to a low dose of nicotine. We speculate that these adverse effects of fetal nicotine exposure may contribute to an increased vulnerability to hypoxic stress in infancy. Results were published in Respiratory Physiology & Neurobiology in 2007.Drs. Sundell, Sandberg and Pinkerton have submitted a manuscript in 2009 for publication in Respiratory Physiology & Neurobiology which describes airway hyper responsiveness to Methacholine inhalation and increased amount of intraepithelial mucosubstances induced by prenatal nicotine exposure in these lambs.

Effects of Nicotine on Respiratory Control
Dr. Sundell has continued to collaborate with our Swedish colleagues, Drs. Joseph Milerad and Ola Hafström, to prepare manuscripts describing results of their studies of pre- and/or postnatal nicotine exposure in young lambs. They are now preparing a manuscript describing the dopaminergic mediation of the impaired ventilatory and arousal responses to acute hypoxemia in prenatally nicotine-exposed lambs.

Group B Streptococcal Toxin/CM101
Dr. Sundell's laboratory, in collaboration with Dr. Carl Hellerqvist of the Department of Biochemistry, is using a sheep model to determine the biological activity (pulmonary hypertension, leukopenia and hyperpyrexia) of material obtained from GBS culture media. The overall aim is to develop a pharmaceutical agent to be used for treatment of cancer, spinal cord injury or other conditions dependent on neovascularization. The therapeutic rationale is based on the anti-neovascular and anti-pathoangiogenic properties possessed by CM101.

Identification of Group B Streptococcal Toxin in Blood from Septic Infants and Their Mothers
This study has been carried out for several years to determine whether a correlation exists between CM101 levels in body fluids and severity of illness of infants with GBS sepsis. Dr. Sundell speculates that severity of illness is not correlated to CM101 levels, as such, but is a manifestation of CM101 binding to CM101 receptors in the pulmonary vasculature. According to preliminary studies these receptors are only expressed in the fetus and shortly after birth. Blood samples have been collected around the time of delivery from mothers of septic infants to determine whether CM101 is present in maternal blood without causing maternal signs of toxemia.

Recent Publications

Cotton RB, Sundell HW, Zeldin DC, Morrow JD, Roberts LJ, Hazinski TA, Law AB, Steele S. Inhaled Nitric Oxide Attenuates Hyperoxic Lung Injury in Lambs Pediatr Res. 2006 Jan;59(1):142-6. Epub 2005 Dec 2.

Sandberg K, Poole SD, Hamdan A, Arbogast P, Sundell HW. Altered Lung Development after Prenatal Exposure in Young Lambs Pediatr Res. 2004 Sep;56(3):432-9. Epub 2004 Jul 7.

Hafstrom O, Milerad J, Sandberg KL, Sundell HW. Cardiorespiratory effects of nicotine exposure during development Respir Physiol Neurobiol. 2005 Nov 15;149(1-3):325-41. Epub 2005 Jun 20. Review.

Downing JW, Ramasubramanian R, Johnson RF, Minzter BH, Paschall RL, Sundell HW, Engelhardt B, Lewis R. Hypothesis: selective phosphodiesterase-5 inhibition improves outcome in preeclampsia Med Hypotheses. 2004;63(6):1057-64.

Sandberg KL, Poole SD, Hamdan A, Minton PA, Sundell HW. Prenatal nicotine exposure transiently alters the lung mechanical response to hypoxia in young lambs. Respir. Physiol. Neurobiol. 156: 283-292, 2007


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