Effect of respiratory syncytial virus on apnea in weanling rats.
Apnea is a common complication of respiratory syncytial virus (RSV) infection in young infants. The purpose of this study was to determine whether this infection affects apnea triggered by sensorineural stimulation in weanling rats. We also studied which neurotransmitters are involved in this response and whether passive prophylaxis with a specific neutralizing antibody (palivizumab) confers protection against it. Weanling rats were inoculated intranasally with RSV, adenovirus, or virus-free medium. Changes in respiratory rate and apnea in response to nerve stimulation with increasing doses of capsaicin were measured by plethysmography. Capsaicin-induced apnea was significantly longer in RSV-infected rats at postinoculation days 2 (upper airways infection) and 5 (lower airways infection), and apnea-related mortality occurred only in the RSV-infected group. Reduction in the duration of apnea was observed after selective inhibition of central gamma-aminobutyric acid (GABA) type A receptors and neurokinin type 1 receptors for substance P. Prophylactic palivizumab protected against apnea and apnea-related mortality. These results suggest that sensorineural stimulation during RSV infection is associated with the development of apnea and apnea-related death in early life, whose mechanism involves the release of GABA acting on central GABA type A receptors and substance P acting on neurokinin type 1 receptors.
Sabogal
Carlos
C
Department of Pediatrics, Division of Pediatric Pulmonology, University of Miami School of Medicine, FL 33136, USA.
Auais
Alexander
A
Napchan
Galia
G
Mager
Edward
E
Zhou
Bo-Guang
BG
Suguihara
Cleide
C
Bancalari
Eduardo
E
Piedimonte
Giovanni
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents / Q000008:administration & dosage; D001049:Apnea / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002211:Capsaicin / Q000633:toxicity; D004279:DNA, Viral / Q000235:genetics; D004558:Electric Stimulation; D018756:GABA Antagonists / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D009500:Neutralization Tests; D000069455:Palivizumab; D051381:Rats; D011916:Rats, Inbred F344; D018357:Respiratory Syncytial Virus Infections / Q000150:complications*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; D004279:DNA, Viral; D018756:GABA Antagonists; D018377:Neurotransmitter Agents; C017069:bicuculline methiodide; D000069455:Palivizumab; D002211:Capsaicin; D001640:Bicuculline