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  • Title: Ventilatory response to drug-induced hypermetabolism.
    Author: Levine S, Huckabee WE.
    Journal: J Appl Physiol; 1975 May; 38(5):827-33. PubMed ID: 1126891.
    Abstract:
    Previous workers have demonstrated that an increase in minute ventilation accompanies tissue hypermetabolism induced by uncouplers of oxidative phosphorylation. The mechanism of this increase in minute ventilation has not been established. Accordingly, 2.5 mg/kg of 2,4-dinitrophenol (DNP) or 8-15 mg/kg of ethyl methylene blue (EMB) were infused into chloralose-anesthetized mongrel dogs; Vo2 increased 105 plus or minus 3% and VE INCREASED 107 PLUS OR MINUS 14%. Heads of vagotomized dogs were then perfused entirely with normal unchanging blood. Spinal cord remained intact. (The carotid bodies lay within the region of the perfused head.) Ventilatory responses of these head-perfused animals to breathing low oxygen and to breathing high CO2 gas mixtures were greatly attenuated. However, when DNP or EMB was infused into the body, VO2 increased 114 plus or minus 23% and VE increased 123 plus or minus 22%. When similar doses of DNP or emb were selectively administered to the head, increases in VE were limited to 21 plus or minus 6%. It is concluded that a major portion of the stimulus to ventilation, which accompanies infusion of DNP or of EMB, arises in tissues other than arterial chemoreceptors and brain. Presumably, this ventilatory stimulus is transmitted to the respiratory center via afferent pathways of the cervical spinal cord.
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