Modification of cerebral blood flow in dogs with doxapram hydrochloride

Abstract

The effects of the respiratory stimulant doxapram HCl on cerebral blood flow (CBF) in dogs have been investigated using a thermocouple. This work was initiated in an effort to explain petechial hemorrhages found in the brains of some animals that were treated chronically with large doses of the drug. When the drug was given intravenously in doses of 5 mg/kg or less, it produced a transient increase in CBF which occurred as the blood pressure was rising, and while the pressure was still elevated a short-lasting decrease in CBF was observed. Larger doses (up to 40 mg/kg) which produced hyperventilation and lowered pCO 2 of arterial peripheral blood, decreased CBF for prolonged periods. Since cerebral vessels are known to constrict in response to hypocapnia and produce tissue anoxia, this appears to be the basis for the petechial hemorrhages. When respiratory responses to doxapram HCl were blocked by tubocurarine Cl or gallamine triethiodide, CBF was increased rather than decreased by the drug. Following removal of the superior cervical ganglia, the initial pressor effect of the drug was more pronounced, but this procedure did not interfere with the subsequent prolonged decrease in CBF. It was concluded that reduction in CBF was due to hypocapnia produced by the doxapram HCl-induced hyperventilation rather than to direct effects of the drug on the blood vessels.