Dissertationen und Habilitationen
Role and mechanisms of carotid and aortic chemosensitivity in the control of breathing of newborn mammals.
Forster, Hubert V.
Medical College of Wisconsin
Carotid body denervation (CBD) in neonatal goats and piglets results in minimal irregular breathing and no fatalities. Redundancy/plasticity of peripheral chemosensitivity and a relatively mature ventilatory control system at birth may contribute to the paucity of CBD effects in these species. In the present dissertation, the role and mechanisms of peripheral chemosensitivity in the ventilatory control system were investigated, testing the following hypotheses: 1.) Mortality would be greater after CBD in neonates of a less mature species such as the rat. 2.) In neonatal piglets that there would be no hypoventilation after sham and aortic denervation (AOD) alone, but there would be transient hypoventilation after CBD and the hypoventilation would be greatest after combined carotid and aortic denervation (CBD+AOD). 3.) Serotonin (5-HT) is involved in chemosensitivity at aortic sites after CBD. We found that the mortality in rats denervated at 2-3 and 7-8 days of age was significantly higher (Pc NaCN response was abolished by prior injections of the polyvalent serotonin-receptor blocker Methiotepin and residual peripheral chemosensitivity after CBD+AOD was localized to the left ventricle. Finally, the aortas from CBD and sham denervated rats and piglets and from AOD and AOD+CBD piglets were harvested, sectioned and studied with immunohistochemistry and western blot techniques. 5-HT immunoreactivity in piglets and rats was concentrated in the endothelium and subendothelial areas in all aortic regions studied, and in some areas also in the adventitia. The immunoreactivity in the proximal portion of the descending aorta in CBD piglets and the ascending aorta in CBD rats was greater than other aortic regions and greater than in other groups studied. The area of increased 5-HT immunoreactivity after CBD co-localized to the area of chemosensitivity after CBD. 5-HT5a receptors were expressed only at the chemosensitive site and only in aortic innervated animals. 5-HT3 receptors were expressed at all aortic sites and in all groups. We concluded that: 1.) CBD has higher mortality in newborn rats than in other mammals, possibly due to the relative immaturity of these animals at birth. Nonetheless, in survivors there was enough redundancy and plasticity in the control of breathing to eventually compensate for the consequences of CBD. 2. ) aortic chemoreceptors contribute to eupneic breathing in piglets that were carotid denervated at less than 5 days of age; 3.) there are multiple sites of residual peripheral chemosensitivity after CBD and 4.) 5-HT acting at 5-HT5a receptors is involved in aortic chemosensitivity of CBD animals.