Carotid artery mixing with diastole-phased pulsed drug infusion

Focal injury to the brain or retina is a frequent complication of drug delivery to the internal carotid artery (ICA) and may be due to poor mixing of the drug with blood at the infusion site. Rhesus monkeys were studied to determine whether phased drug delivery during diastole from a modified pulsatile angiographic injector would improve drug mixing in vivo. A radiolabeled flow tracer, carbon-14-iodoantipyrine (14C-IAP), was injected into the ICA of three monkeys in 80-msec pulses, each ending at least 50 msec before the end of local diastole. Local isotope concentration in the brain was determined by quantitative autoradiography. The ratio of highest to lowest concentration was 1.86 +/- 0.26 (mean +/- standard deviation) in the frontoparietal cortex, 1.65 +/- 0.42 in the frontoparietal white matter, 1.89 +/- 0.28 in the temporal cortex, and 1.39 +/- 0.17 in the basal ganglia. These results were similar to recordings in three control animals that received intravenous 14C-IAP to demonstrate complete drug mixing (1.37 +/- 0.12, 1.41 +/- 0.11, 1.70 +/- 0.08, 1.22 +/- 0.24, respectively), and contrasted to findings in five animals which received continuous intracarotid infusions to demonstrate standard ICA drug delivery (4.54 +/- 2.07, 2.94 +/- 1.45, 5.43 +/- 3.57, 3.60 +/- 2.90, respectively). Pulsed intra-arterial infusion during diastole provides a technically simple method for improving intravascular drug mixing, and results in drug delivery to tissue capillaries that is proportional to blood flow.