Transcranial Doppler sonography: a new noninvasive method for measuring toxicant-induced alterations in cerebral blood flow

Drues, Michael
Major Professor
David L. Hopper
David L. Carlson
Committee Member
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Chemical and Biological Engineering

The purpose of this experiment was to use transcranial Doppler sonography (TCD) in the dog to noninvasively measure changes in cerebral blood flow (CBF) resulting from a low-level exposure to the commonly used pyrethroid insecticide deltamethrin. Deltamethrin has previously been shown to increase CBF in rats as determined by other techniques. In this experiment, deltamethrin was dissolved in glycerol-formal solvent and administered intravenously at dosage levels of 5% and 10% of the LD[subscript]50 value to 12 adult dogs 48 hours apart. It was expected that vascular changes resulting from these low-level deltamethrin exposures would be subtle and occur over several minutes (rather than beat-to-beat changes). To test this hypothesis, mean blood flow velocity (MBFV) in the middle cerebral artery, mean arterial blood pressure (MAP) in the aorta, end tidal CO[subscript]2 (pCO[subscript]2), mean heart rate (MHR) and concentration of deltamethrin in the blood were measured during control, glycerol-formal and exposure (deltamethrin in glycerol-formal) periods according to a randomized block factorial design. In addition to the aforementioned parameters, systolic-to-diastolic ratio (SDR), Pourcelout pulsatility index (PPI), Gosling pulsatility index (GPI) and systolic upstroke (SU) were calculated using the blood flow velocity waveform. Following the administration of deltamethrin, there was a significant increase in MBFV lasting 10 minutes post exposure, a significant increase in MAP and decrease in MHR lasting 20 minutes post exposure and a significant increase in pCO[subscript]2 lasting 30 minutes post exposure. The increase in MBFV was expected and corroborates the increase in CBF previously observed in rats. These changes indicate that the deltamethrin was having systemic effects on the cardiovascular and cerebrovascular systems. Further, this data agrees with circulating deltamethrin concentrations in the blood which peaked approximately 5 minutes post exposure. SDR, PPI and GPI returned to control levels following the administration of deltamethrin. TCD seems to have significant potential as a screening methodology, however, to date it has not been used with animals nor has it been applied in the field of toxicology. In this research, it has been shown that TCD is sensitive to alterations in CBF caused by deltamethrin in the greyhound dog. (Abstract shortened with permission of author.)