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Chemoreflex Responses to LPS Exposure During a Critical Window of Development in the in situ Arterially Perfused Working Heart Brainstem Preparation
Author(s) -
Kola Gjinovefa,
Chadha Priyal,
Mayer Catherine A.,
Dick Thomas E.,
Dutschmann Mathias,
Lewis Stephen J.,
MacFarlane Peter M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.742.8
Subject(s) - medicine , heart rate , brainstem , respiratory system , phrenic nerve , anesthesia , perfusion , respiratory rate , autonomic nervous system , lipopolysaccharide , chemoreceptor , blood pressure , endocrinology , receptor
The second week of postnatal life represents a critical window of brainstem cardio‐respiratory neural development in rats. We showed previously that endotoxin (lipopolysaccharide, LPS) exposure during this critical period of development (specifically at P10 days of age) attenuated the acute hypoxic ventilatory response and increased brainstem cytokine mRNA expression; these effects of LPS were also associated with an unexpected increase in mortality. These data suggest there may be a critical window of development during which the (cardio)‐respiratory control system exhibits a heightened vulnerability to inflammatory challenges. The potential impact of LPS exposure on neural control of cardio‐respiratory function during this critical window of development is unknown. We used the in situ arterially perfused working heart brainstem preparation to investigate how LPS affects central nervous control of respiratory and autonomic function in P10 rats. Two hours after an intraperitoneal injection of LPS (0.1mg/kg, n=24), rats were surgically prepared for chemoreceptor mediated sympathoexcitation by measuring phrenic, vagal, and thoracic sympathetic nerve responses to an intra‐arterially injection of sodium cyanide (75 μl, 0.03% NaCN). Rats were also cannulated for measurements of heart rate and arterial/perfusion pressure. Compared to saline treated controls, LPS decreased baseline phrenic nerve burst frequency by 27% and increased vagal nerve activity by 76% (peak amplitude). Baseline thoracic sympathetic nerve activity, heart rate and arterial perfusion pressure were similar between treatment groups. Although NaCN increased respiratory frequency and vagal nerve activity in both groups, the frequency response was attenuated by 35% in LPS treated rats. The magnitude of the thoracic sympathetic nerve and bradycardic response to NaCN was not affected by LPS treatment. These data indicate that LPS depresses baseline respiratory network function and impairs vital respiratory response to arterial chemoreceptor activation. In conclusion, the present data suggest that inflammatory challenges during a critical period of development trigger potentially fatal instabilities in respiratory network function. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .